Fabrication of triple-layered bifurcated vascular scaffold with a certain degree of three-dimensional structure

NASA Astrophysics Data System (ADS)

Liu, Yuanyuan; Jiang, Weijian; Yang, Yang; Pu, Huayan; Peng, Yan; Xin, Liming; Zhang, Yi; Sun, Yu

2018-01-01

Constructing vascular scaffolds is important in tissue engineering. However, scaffolds with characteristics such as multiple layers and a certain degree of spatial morphology still cannot be readily constructed by current vascular scaffolds fabrication techniques. This paper presents a three-layered bifurcated vascular scaffold with a curved structure. The technique combines 3D printed molds and casting hydrogel and fugitive ink to create vessel-mimicking constructs with customizable structural parameters. Compared with other fabrication methods, the technique can create more native-like 3D geometries. The diameter and wall thickness of the fabricated constructs can be independently controlled, providing a feasible approach for vascular scaffold construction. Enzymatically-crosslinked gelatin was used as the scaffold material. The morphology and mechanical properties were evaluated. Human umbilical cord derived endothelial cells (HUVECs) were seeded on the scaffolds and cultured for 72 h. Cell viability and morphology were assessed. The results showed that the proposed process had good application potentials, and will hopefully provide a feasible approach for constructing vascular scaffolds.

Raman imaging to investigate ultrastructure and composition of plant cell walls : distribution of lignin and cellulose in black spruce wood (Picea mariana)

Treesearch

Umesh P. Agarwal

2006-01-01

A detailed understanding of the structural organization of the cell wall of vascular plants is important from both the perspectives of plant biology and chemistry and of commercial utilization. A state-of-the-art 633-nm laser-based confocal Raman microscope was used to determine the distribution of cell wall components in the cross section of black spruce wood in situ...

Stomatal cell wall composition: distinctive structural patterns associated with different phylogenetic groups.

PubMed

Shtein, Ilana; Shelef, Yaniv; Marom, Ziv; Zelinger, Einat; Schwartz, Amnon; Popper, Zoë A; Bar-On, Benny; Harpaz-Saad, Smadar

2017-04-01

Stomatal morphology and function have remained largely conserved throughout ∼400 million years of plant evolution. However, plant cell wall composition has evolved and changed. Here stomatal cell wall composition was investigated in different vascular plant groups in attempt to understand their possible effect on stomatal function. A renewed look at stomatal cell walls was attempted utilizing digitalized polar microscopy, confocal microscopy, histology and a numerical finite-elements simulation. The six species of vascular plants chosen for this study cover a broad structural, ecophysiological and evolutionary spectrum: ferns ( Asplenium nidus and Platycerium bifurcatum ) and angiosperms ( Arabidopsis thaliana and Commelina erecta ) with kidney-shaped stomata, and grasses (angiosperms, family Poaceae) with dumbbell-shaped stomata ( Sorghum bicolor and Triticum aestivum ). Three distinct patterns of cellulose crystallinity in stomatal cell walls were observed: Type I (kidney-shaped stomata, ferns), Type II (kidney-shaped stomata, angiosperms) and Type III (dumbbell-shaped stomata, grasses). The different stomatal cell wall attributes investigated (cellulose crystallinity, pectins, lignin, phenolics) exhibited taxon-specific patterns, with reciprocal substitution of structural elements in the end-walls of kidney-shaped stomata. According to a numerical bio-mechanical model, the end walls of kidney-shaped stomata develop the highest stresses during opening. The data presented demonstrate for the first time the existence of distinct spatial patterns of varying cellulose crystallinity in guard cell walls. It is also highly intriguing that in angiosperms crystalline cellulose appears to have replaced lignin that occurs in the stomatal end-walls of ferns serving a similar wall strengthening function. Such taxon-specific spatial patterns of cell wall components could imply different biomechanical functions, which in turn could be a consequence of differences in environmental selection along the course of plant evolution. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

The use of Intravenous Laser Blood Irradiation (ILBI) at 630–640 nm to prevent vascular diseases and to increase life expectancy

PubMed Central

2015-01-01

Background and Aims: The mortality rate from vascular diseases is one of the highest. The use of Intravenous Laser Blood Irradiation (ILBI) within the last 30 years has demonstrated high efficacy in the treatment of vascular, cardiac and other systemic diseases. Rationale: Laser energy at 630-640 nanometers is arguably the most effective for irradiation of blood and the vascular wall. Photons at this wavelength are absorbed by oxygen, improve microcirculation, can change the viscosity of the blood and affect vascular endothelium. Conclusions: In summary, more than 25 years of experience of using laser energy at 630-640 nm has shown that this waveband directly influences the parameters of all cells in the blood, blood plasma, the coagulation process and all the structural components of the vascular wall. Additionally, ILBI directly or indirectly affects the cells of the immune system, hormones, and exchange processes in an organism, thereby not only improving the function of the vascular system, but also the other systems of an organism. It can finally lead to lower the incidence and number of vascular diseases, and indirectly to the reduction of the number of diseases in other organs and even systemically, thus helping to prolong the lifespan. PMID:25941421

[Stem and progenitor cells in biostructure of blood vessel walls].

PubMed

Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

2013-09-18

Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

Simulations of Congenital Septal Defect Closure and Reactivity Testing in Patient-Specific Models of the Pediatric Pulmonary Vasculature: A 3D Numerical Study With Fluid-Structure Interaction

PubMed Central

Hunter, Kendall S.; Lanning, Craig J.; Chen, Shiuh-Yung J.; Zhang, Yanhang; Garg, Ruchira; Ivy, D. Dunbar; Shandas, Robin

2014-01-01

Clinical imaging methods are highly effective in the diagnosis of vascular pathologies, but they do not currently provide enough detail to shed light on the cause or progression of such diseases, and would be hard pressed to foresee the outcome of surgical interventions. Greater detail of and prediction capabilities for vascular hemodynamics and arterial mechanics are obtained here through the coupling of clinical imaging methods with computational techniques. Three-dimensional, patient-specific geometric reconstructions of the pediatric proximal pulmonary vasculature were obtained from x-ray angiogram images and meshed for use with commercial computational software. Two such models from hypertensive patients, one with multiple septal defects, the other who underwent vascular reactivity testing, were each completed with two sets of suitable fluid and structural initial and boundary conditions and used to obtain detailed transient simulations of artery wall motion and hemodynamics in both clinically measured and predicted configurations. The simulation of septal defect closure, in which input flow and proximal vascular stiffness were decreased, exhibited substantial decreases in proximal velocity, wall shear stress (WSS), and pressure in the post-op state. The simulation of vascular reactivity, in which distal vascular resistance and proximal vascular stiffness were decreased, displayed negligible changes in velocity and WSS but a significant drop in proximal pressure in the reactive state. This new patient-specific technique provides much greater detail regarding the function of the pulmonary circuit than can be obtained with current medical imaging methods alone, and holds promise for enabling surgical planning. PMID:16813447

Microfluidic strategy to investigate dynamics of small blood vessel function

NASA Astrophysics Data System (ADS)

Yasotharan, Sanjesh; Bolz, Steffen-Sebastian; Guenther, Axel

2010-11-01

Resistance arteries (RAs, 30-300 microns in diameter) that are located within the terminal part of the vascular tree regulate the laminar perfusion of tissue with blood, via the peripheral vascular resistance, and hence controls the systemic blood pressure. The structure of RAs is adapted to actively controlling flow resistance by dynamically changing their diameter, which is non-linearly dependent on the temporal variation of the transmural pressure, perfusion flow rate and spatiotemporal changes in the chemical environment. Increases in systemic blood pressure (hypertension) resulting from pathologic changes in the RA response represent the primary risk factor for cardiovascular diseases. We use a microfluidic strategy to investigate small blood vessels by quantifying structural variations within the arterial wall, RA outer contour and diameter over time. First, we document the artery response to vasomotor drugs that were homogeneously applied at step-wise increasing concentration. Second, we investigate the response in the presence of well-defined axial and circumferential heterogeneities. Artery per- and superfusion is discussed based on microscale PIV measurements of the fluid velocity on both sides of the arterial wall. Structural changes in the arterial wall are quantified using cross-correlation and proper orthogonal decomposition analyses of bright-field micrographs.

Detection of Aortic Wall Inclusion Using Regional Pulse Wave Propagation and Velocity In Silico

PubMed Central

Shahmirzadi, Danial; Konofagou, Elisa E.

2012-01-01

Monitoring of the regional stiffening of the arterial wall may prove important in the diagnosis of various vascular pathologies. The pulse wave velocity (PWV) along the aortic wall has been shown to be dependent on the wall stiffness and has played a fundamental role in a range of diagnostic methods. Conventional clinical methods involve a global examination of the pulse traveling between two remote sites, e.g. femoral and carotid arteries, to provide an average PWV estimate. However, the majority of vascular diseases entail regional vascular changes and therefore may not be detected by a global PWV estimate. In this paper, a fluid-structure interaction study of straight-geometry aortas was carried out to examine the effects of regional stiffness changes on PWV. Five homogeneous aortas with increasing wall stiffness as well as two aortas with soft and hard inclusions were considered. In each case, spatio-temporal maps of the wall motion were used to analyze the regional pulse wave propagation. On the homogeneous aortas, increasing PWVs were found to increase with the wall moduli (R2 = 0.9988), indicating the reliability of the model to accurately represent the wave propagation. On the inhomogeneous aortas, formation of reflected and standing waves was observed at the site of the hard and soft inclusions, respectively. Neither the hard nor the soft inclusion had a significant effect on the velocity of the traveling pulse beyond the inclusion site, which supported the hypothesis that a global measurement of the average PWV could fail to detect regional abnormalities. PMID:24235978

A tale of two neglected systems-structure and function of the thin- and thick-walled sieve tubes in monocotyledonous leaves.

PubMed

Botha, C E J

2013-01-01

There is a large body of information relating to the ontogeny, development and the vasculature of eudicotyledonous leaves. However, there is less information available concerning the vascular anatomy of monocotyledonous leaves. This is surprising, given that there are two uniquely different phloem systems present in large groups such as grasses and sedges. Monocotyledonous leaves contain marginal, large, intermediate, and small longitudinal veins that are interconnected by numerous transverse veins. The longitudinal veins contain two metaphloem sieve tube types, which, based upon their ontogeny and position within the phloem, are termed early (thin-walled) and late (thick-walled) sieve tubes. Early metaphloem comprises sieve tubes, companion cells and vascular parenchyma (VP) cells, whilst the late metaphloem, contains thick-walled sieve tubes (TSTs) that lack companion cells. TSTs are generally adjacent to, or no more than one cell removed from the metaxylem. Unlike thin-walled sieve tube (ST) -companion cell complexes, TSTs are connected to parenchyma by pore-plasmodesma units and are generally symplasmically isolated from the STs. This paper addresses key structural and functional differences between thin- and thick-walled sieve tubes and explores the unique advantages of alternate transport strategies that this 5-7 million years old dual system may offer. It would seem that these two systems may enhance, add to, or play a significant role in increasing the efficiency of solute retrieval as well as of assimilate transfer.

A tale of two neglected systems—structure and function of the thin- and thick-walled sieve tubes in monocotyledonous leaves

PubMed Central

Botha, C. E. J.

2013-01-01

There is a large body of information relating to the ontogeny, development and the vasculature of eudicotyledonous leaves. However, there is less information available concerning the vascular anatomy of monocotyledonous leaves. This is surprising, given that there are two uniquely different phloem systems present in large groups such as grasses and sedges. Monocotyledonous leaves contain marginal, large, intermediate, and small longitudinal veins that are interconnected by numerous transverse veins. The longitudinal veins contain two metaphloem sieve tube types, which, based upon their ontogeny and position within the phloem, are termed early (thin-walled) and late (thick-walled) sieve tubes. Early metaphloem comprises sieve tubes, companion cells and vascular parenchyma (VP) cells, whilst the late metaphloem, contains thick-walled sieve tubes (TSTs) that lack companion cells. TSTs are generally adjacent to, or no more than one cell removed from the metaxylem. Unlike thin-walled sieve tube (ST) -companion cell complexes, TSTs are connected to parenchyma by pore-plasmodesma units and are generally symplasmically isolated from the STs. This paper addresses key structural and functional differences between thin- and thick-walled sieve tubes and explores the unique advantages of alternate transport strategies that this 5–7 million years old dual system may offer. It would seem that these two systems may enhance, add to, or play a significant role in increasing the efficiency of solute retrieval as well as of assimilate transfer. PMID:23964280

Disrupting Flavone Synthase II Alters Lignin and Improves Biomass Digestibility1[OPEN

PubMed Central

Takeda, Yuri; Yamamura, Masaomi

2017-01-01

Lignin, a ubiquitous phenylpropanoid polymer in vascular plant cell walls, is derived primarily from oxidative couplings of monolignols (p-hydroxycinnamyl alcohols). It was discovered recently that a wide range of grasses, including cereals, utilize a member of the flavonoids, tricin (3′,5′-dimethoxyflavone), as a natural comonomer with monolignols for cell wall lignification. Previously, we established that cytochrome P450 93G1 is a flavone synthase II (OsFNSII) indispensable for the biosynthesis of soluble tricin-derived metabolites in rice (Oryza sativa). Here, our tricin-deficient fnsII mutant was analyzed further with an emphasis on its cell wall structure and properties. The mutant is similar in growth to wild-type control plants with normal vascular morphology. Chemical and nuclear magnetic resonance structural analyses demonstrated that the mutant lignin is completely devoid of tricin, indicating that FNSII activity is essential for the deposition of tricin-bound lignin in rice cell walls. The mutant also showed substantially reduced lignin content with decreased syringyl/guaiacyl lignin unit composition. Interestingly, the loss of tricin in the mutant lignin appears to be partially compensated by incorporating naringenin, which is a preferred substrate of OsFNSII. The fnsII mutant was further revealed to have enhanced enzymatic saccharification efficiency, suggesting that the cell wall recalcitrance of grass biomass may be reduced through the manipulation of the flavonoid monomer supply for lignification. PMID:28385728

Structural determinants of vascular resistance properties in hypertension. Haemodynamic and model analysis.

PubMed

Korner, P I; Angus, J A

1992-01-01

The average internal radius (ri) of the resistance vessels of the hindquarter (HQ) bed was narrower in renovascular and genetic hypertension than in normotensive controls. The narrowing was approximately uniform over the full range of vasomotor tone, which accounted for the bed's property as an 'amplifier' of vascular resistance (R) (increased slope (S) of the dose-R response curve) and for the elevated R at maximum dilatation (Rmin). In the model we examined the effects on the dose-R curve parameters of altering wall/internal radius (w/ri) ratio, ri and wall 'stiffness' one at a time, whilst the others were held constant: only narrowing of ri led to increases in both S and Rmin; with hypertrophy alone, S increased but Rmin was reduced, whilst increased wall stiffness increased Rmin but lowered S. Thus, for hypertrophy to be associated with rises of both S and Rmin, it must be linked to lumen narrowing, to increased wall stiffness, or to both. Preferential deposition of new material towards the lumen will link hypertrophy to narrowing. It has been suggested that narrowing can occur without hypertrophy ('remodelling'). In the model an increase of only 1-2% WV was required to produce rises in w/ri of congruent to 30-50% when associated with congruent to 10-15% reduction in ri, which is close to the limit of detection. From the literature, the sites of greater narrowing in hypertension extend down to small arteries and large arterioles. The rise in BP upstream from those sites, due to the vascular amplifier, offsets the down-stream effects of vascular narrowing on blood flow and this negative feedback system helps to maintain elevation of BP at a stable level. We also examined developmental rise in R between 4 and 50 weeks, which affected SHR and WKY in the same proportion: structural factors (vascular length of larger arteries, 'rarefaction' of arterioles and capillaries) accounted for only about half the rise in R, and the remainder was probably due to developmental changes in muscle function.

A method for semi-automatic segmentation and evaluation of intracranial aneurysms in bone-subtraction computed tomography angiography (BSCTA) images

NASA Astrophysics Data System (ADS)

Krämer, Susanne; Ditt, Hendrik; Biermann, Christina; Lell, Michael; Keller, Jörg

2009-02-01

The rupture of an intracranial aneurysm has dramatic consequences for the patient. Hence early detection of unruptured aneurysms is of paramount importance. Bone-subtraction computed tomography angiography (BSCTA) has proven to be a powerful tool for detection of aneurysms in particular those located close to the skull base. Most aneurysms though are chance findings in BSCTA scans performed for other reasons. Therefore it is highly desirable to have techniques operating on standard BSCTA scans available which assist radiologists and surgeons in evaluation of intracranial aneurysms. In this paper we present a semi-automatic method for segmentation and assessment of intracranial aneurysms. The only user-interaction required is placement of a marker into the vascular malformation. Termination ensues automatically as soon as the segmentation reaches the vessels which feed the aneurysm. The algorithm is derived from an adaptive region-growing which employs a growth gradient as criterion for termination. Based on this segmentation values of high clinical and prognostic significance, such as volume, minimum and maximum diameter as well as surface of the aneurysm, are calculated automatically. the segmentation itself as well as the calculated diameters are visualised. Further segmentation of the adjoining vessels provides the means for visualisation of the topographical situation of vascular structures associated to the aneurysm. A stereolithographic mesh (STL) can be derived from the surface of the segmented volume. STL together with parameters like the resiliency of vascular wall tissue provide for an accurate wall model of the aneurysm and its associated vascular structures. Consequently the haemodynamic situation in the aneurysm itself and close to it can be assessed by flow modelling. Significant values of haemodynamics such as pressure onto the vascular wall, wall shear stress or pathlines of the blood flow can be computed. Additionally a dynamic flow model can be generated. Thus the presented method supports a better understanding of the clinical situation and assists the evaluation of therapeutic options. Furthermore it contributes to future research addressing intervention planning and prognostic assessment of intracranial aneurysms.

Cell Based Therapeutic Approach in Vascular Surgery: Application and Review

PubMed Central

Rocca, Aldo; Tafuri, Domenico; Paccone, Marianna; Giuliani, Antonio; Zamboli, Anna Ginevra Immacolata; Surfaro, Giuseppe; Paccone, Andrea; Compagna, Rita; Amato, Maurizo; Serra, Raffaele; Amato, Bruno

2017-01-01

Abstract Multipotent stem cells - such as mesenchymal stem/stromal cells and stem cells derived from different sources like vascular wall are intensely studied to try to rapidly translate their discovered features from bench to bedside. Vascular wall resident stem cells recruitment, differentiation, survival, proliferation, growth factor production, and signaling pathways transduced were analyzed. We studied biological properties of vascular resident stem cells and explored the relationship from several factors as Matrix Metalloproteinases (MMPs) and regulations of biological, translational and clinical features of these cells. In this review we described a translational and clinical approach to Adult Vascular Wall Resident Multipotent Vascular Stem Cells (VW-SCs) and reported their involvement in alternative clinical approach as cells based therapy in vascular disease like arterial aneurysms or peripheral arterial obstructive disease. PMID:29071303

Cerebral vascular structure in the motor cortex of adult mice is stable and is not altered by voluntary exercise.

PubMed

Cudmore, Robert H; Dougherty, Sarah E; Linden, David J

2017-12-01

The cerebral vasculature provides blood flow throughout the brain, and local changes in blood flow are regulated to match the metabolic demands of the active brain regions. This neurovascular coupling is mediated by real-time changes in vessel diameter and depends on the underlying vascular network structure. Neurovascular structure is configured during development by genetic and activity-dependent factors. In adulthood, it can be altered by experiences such as prolonged hypoxia, sensory deprivation and seizure. Here, we have sought to determine whether exercise could alter cerebral vascular structure in the adult mouse. We performed repeated in vivo two-photon imaging in the motor cortex of adult transgenic mice expressing membrane-anchored green fluorescent protein in endothelial cells (tyrosine endothelial kinase 2 receptor (Tie2)-Cre:mTmG). This strategy allows for high-resolution imaging of the vessel walls throughout the lifespan. Vascular structure, as measured by capillary branch point number and position, segment diameter and length remained stable over a time scale of months as did pericyte number and position. Furthermore, we compared the vascular structure before, during, and after periods of voluntary wheel running and found no alterations in these same parameters. In both running and control mice, we observed a low rate of capillary segment subtraction. Interestingly, these rare subtraction events preferentially remove short vascular loops.

Elastin aging and lipid oxidation products in human aorta.

PubMed

Zarkovic, Kamelija; Larroque-Cardoso, Pauline; Pucelle, Mélanie; Salvayre, Robert; Waeg, Georg; Nègre-Salvayre, Anne; Zarkovic, Neven

2015-01-01

Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from structural modifications of the extracellular matrix (ECM) components. Among the factors known to accumulate with aging, advanced lipid peroxidation end products (ALEs) are a hallmark of oxidative stress-associated diseases such as atherosclerosis. Aldehydes generated from the peroxidation of polyunsaturated fatty acids (PUFA), (4-hydroxynonenal, malondialdehyde, acrolein), form adducts on cellular proteins, leading to a progressive protein dysfunction with consequences in the pathophysiology of vascular aging. The contribution of these aldehydes to ECM modification is not known. This study was carried out to investigate whether aldehyde-adducts are detected in the intima and media in human aorta, whether their level is increased in vascular aging, and whether elastin fibers are a target of aldehyde-adduct formation. Immunohistological and confocal immunofluorescence studies indicate that 4-HNE-histidine-adducts accumulate in an age-related manner in the intima, media and adventitia layers of human aortas, and are mainly expressed in smooth muscle cells. In contrast, even if the structure of elastin fiber is strongly altered in the aged vessels, our results show that elastin is not or very poorly modified by 4-HNE. These data indicate a complex role for lipid peroxidation and in particular for 4-HNE in elastin homeostasis, in the vascular wall remodeling during aging and atherosclerosis development. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Elastin aging and lipid oxidation products in human aorta

PubMed Central

Zarkovic, Kamelija; Larroque-Cardoso, Pauline; Pucelle, Mélanie; Salvayre, Robert; Waeg, Georg; Nègre-Salvayre, Anne; Zarkovic, Neven

2014-01-01

Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from structural modifications of the extracellular matrix (ECM) components. Among the factors known to accumulate with aging, advanced lipid peroxidation end products (ALEs) are a hallmark of oxidative stress-associated diseases such as atherosclerosis. Aldehydes generated from the peroxidation of polyunsaturated fatty acids (PUFA), (4-hydroxynonenal, malondialdehyde, acrolein), form adducts on cellular proteins, leading to a progressive protein dysfunction with consequences in the pathophysiology of vascular aging. The contribution of these aldehydes to ECM modification is not known. This study was carried out to investigate whether aldehyde-adducts are detected in the intima and media in human aorta, whether their level is increased in vascular aging, and whether elastin fibers are a target of aldehyde-adduct formation. Immunohistological and confocal immunofluorescence studies indicate that 4-HNE-histidine-adducts accumulate in an age-related manner in the intima, media and adventitia layers of human aortas, and are mainly expressed in smooth muscle cells. In contrast, even if the structure of elastin fiber is strongly altered in the aged vessels, our results show that elastin is not or very poorly modified by 4-HNE. These data indicate a complex role for lipid peroxidation and in particular for 4-HNE in elastin homeostasis, in the vascular wall remodeling during aging and atherosclerosis development. PMID:25553420

Vascular Wall-Resident Multipotent Stem Cells of Mesenchymal Nature within the Process of Vascular Remodeling: Cellular Basis, Clinical Relevance, and Implications for Stem Cell Therapy.

PubMed

Klein, Diana

2016-01-01

Until some years ago, the bone marrow and the endothelial cell compartment lining the vessel lumen (subendothelial space) were thought to be the only sources providing vascular progenitor cells. Now, the vessel wall, in particular, the vascular adventitia, has been established as a niche for different types of stem and progenitor cells with the capacity to differentiate into both vascular and nonvascular cells. Herein, vascular wall-resident multipotent stem cells of mesenchymal nature (VW-MPSCs) have gained importance because of their large range of differentiation in combination with their distribution throughout the postnatal organism which is related to their existence in the adventitial niche, respectively. In general, mesenchymal stem cells, also designated as mesenchymal stromal cells (MSCs), contribute to the maintenance of organ integrity by their ability to replace defunct cells or secrete cytokines locally and thus support repair and healing processes of the affected tissues. This review will focus on the central role of VW-MPSCs within vascular reconstructing processes (vascular remodeling) which are absolute prerequisite to preserve the sensitive relationship between resilience and stability of the vessel wall. Further, a particular advantage for the therapeutic application of VW-MPSCs for improving vascular function or preventing vascular damage will be discussed.

Detection and description of various stores of nitric oxide store in vascular wall.

PubMed

Vlasova, M A; Vanin, A F; Muller, B; Smirin, B V; Malyshev, I Yu; Manukhina, E B

2003-09-01

We analyzed the possibility of the existence of various NO pools in the vascular wall. Incubation of isolated rat aorta with dinitrosyl iron complex (NO donor) led to the formation of NO stores in the vascular wall detected by vascular relaxation response induced by diethyldithiocarbamate and N-acetylcysteine. Comparison of the effects of successive application of diethyldithiocarbamate and N-acetylcysteine revealed two NO pools (one pool responded to both agents, while other responded only to N-acetylcysteine). Inhibition of guanylate cyclase with methylene blue abolished the response to diethyldithiocarbamate, while the reaction to N-acetylcysteine decreased by the value, corresponding to diethyldithiocarbamate-dependent relaxation. It is hypothesized that in the vascular wall NO is stored in the form protein-bound dinitrosyl iron complexes and S-nitrosothiols in hydrophilic and hydrophobic cell compartments.

Comparative characterization of stromal vascular cells derived from three types of vascular wall and adipose tissue.

PubMed

Yang, Santsun; Eto, Hitomi; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Kinoshita, Kahori; Ma, Hsu; Tsai, Chi-Han; Chou, Wan-Ting; Yoshimura, Kotaro

2013-12-01

Multipotent stem/progenitor cells localize perivascularly in many organs and vessel walls. These tissue-resident stem/progenitor cells differentiate into vascular endothelial cells, pericytes, and other mesenchymal lineages, and participate in physiological maintenance and repair of vasculatures. In this study, we characterized stromal vascular cells obtained through the explant culture method from three different vessel walls in humans: arterial wall (ART; >500 μm in diameter), venous wall (VN; >500 μm in diameter), and small vessels in adipose tissue (SV; arterioles and venules, <100 μm in diameter). These were examined for functionality and compared with adipose-derived stem/stromal cells (ASCs). All stromal vascular cells of different origins presented fibroblast-like morphology and we could not visually discriminate one population from another. Flow cytometry showed that the cultured population heterogeneously expressed a variety of surface antigens associated with stem/progenitor cells, but CD105 was expressed by most cells in all groups, suggesting that the cells generally shared the characteristics of mesenchymal stem cells. Our histological and flow cytometric data suggested that the main population of vessel wall-derived stromal vascular cells were CD34(+)/CD31(-) and came from the tunica adventitia and areola tissue surrounding the adventitia. CD271 (p75NTR) was expressed by the vasa vasorum in the VN adventitia and by a limited population in the adventitia of SV. All three populations differentiated into multiple lineages as did ASCs. ART cells induced the largest quantity of calcium formation in the osteogenic medium, whereas ASCs showed the greatest adipogenic differentiation. SV and VN stromal cells had greater potency for network formation than did ART stromal cells. In conclusion, the three stromal vascular populations exhibited differential functional properties. Our results have clinical implications for vascular diseases such as arterial wall calcification and possible applications to regenerative therapies involving each vessel wall-resident stromal population.

Dianthus chinensis L.: The Structural Difference between Vascular Bundles in the Placenta and Ovary Wall Suggests Their Different Origin

PubMed Central

Guo, Xue-Min; Yu, Ying-Ying; Bai, Lan; Gao, Rong-Fu

2017-01-01

Dianthus chinensis is a perennial herbaceous plant with great ornamental, botanical, ecological, and medicinal value. The pistil of D. chinensis is composed of two fused carpels with free central placenta and two separate styles. The placenta is a columnar structure extending about two-thirds the length of the maturing fruit, which is typical of the Caryophyllaceous. Traditionally, free central placenta is thought to have evolved from axial placenta by septal disappearance, and axial placenta to have occurred through fusion of conduplicate carpels with marginal placenta. However, the traditional opinion is becoming more and more inconsistent with the new data gained in recent research of angiosperm systematics. To clarify the origin of D. chinensis pistil, the present anatomical study was carried out. The results show that the vascular system of placenta is independent to that of the ovary wall in D. chinensis. Moreover, in the central part of placenta there are one or two amphicribral bundles, and correspondingly numerous ones in the pistil which supply the ovules/seeds. It is obvious that the central amphicribral bundles in placenta are comparable to the counterparts in branches but not to those in leaves or their derivatives. Therefore, it is reasonable to deduce that the placenta of D. chinensis was not derived from conduplicate carpels through fusion of collateral vascular bundles, and actually a floral axis with ovules/seeds laterally adhering. On the contrary, the ovary wall was the lateral appendages of the floral axis. The result of the present study is completely in agreement with Unifying Theory, in which the placenta is taken as an ovule-bearing branch. Except for D. chinensis, the similar vascular organization has been observed in placenta of numerous isolated taxa. But till now, it is uncertain that whether this vascular organization pattern is popular in the whole angiosperms or not. More intensive and extensive investigations are needed. PMID:29250086

Dianthus chinensis L.: The Structural Difference between Vascular Bundles in the Placenta and Ovary Wall Suggests Their Different Origin.

PubMed

Guo, Xue-Min; Yu, Ying-Ying; Bai, Lan; Gao, Rong-Fu

2017-01-01

Dianthus chinensis is a perennial herbaceous plant with great ornamental, botanical, ecological, and medicinal value. The pistil of D. chinensis is composed of two fused carpels with free central placenta and two separate styles. The placenta is a columnar structure extending about two-thirds the length of the maturing fruit, which is typical of the Caryophyllaceous. Traditionally, free central placenta is thought to have evolved from axial placenta by septal disappearance, and axial placenta to have occurred through fusion of conduplicate carpels with marginal placenta. However, the traditional opinion is becoming more and more inconsistent with the new data gained in recent research of angiosperm systematics. To clarify the origin of D. chinensis pistil, the present anatomical study was carried out. The results show that the vascular system of placenta is independent to that of the ovary wall in D. chinensis . Moreover, in the central part of placenta there are one or two amphicribral bundles, and correspondingly numerous ones in the pistil which supply the ovules/seeds. It is obvious that the central amphicribral bundles in placenta are comparable to the counterparts in branches but not to those in leaves or their derivatives. Therefore, it is reasonable to deduce that the placenta of D. chinensis was not derived from conduplicate carpels through fusion of collateral vascular bundles, and actually a floral axis with ovules/seeds laterally adhering. On the contrary, the ovary wall was the lateral appendages of the floral axis. The result of the present study is completely in agreement with Unifying Theory, in which the placenta is taken as an ovule-bearing branch. Except for D. chinensis , the similar vascular organization has been observed in placenta of numerous isolated taxa. But till now, it is uncertain that whether this vascular organization pattern is popular in the whole angiosperms or not. More intensive and extensive investigations are needed.

Impact of CCR1 silencing on the assembly of lignified secondary walls in Arabidopsis thaliana.

PubMed

Ruel, Katia; Berrio-Sierra, Jimmy; Derikvand, Mohammad Mir; Pollet, Brigitte; Thévenin, Johanne; Lapierre, Catherine; Jouanin, Lise; Joseleau, Jean-Paul

2009-01-01

A cinnamoyl-CoA reductase 1 knockout mutant in Arabidopsis thaliana was investigated for the consequences of lignin synthesis perturbation on the assembly of the cell walls. The mutant displayed a dwarf phenotype and a strong collapse of its xylem vessels corresponding to lower lignin content and a loss of lignin units of the noncondensed type. Transmission electron microscopy revealed that the transformation considerably impaired the capacity of interfascicular fibers and vascular bundles to complete the assembly of cellulose microfibrils in the S(2) layer, the S(1) layer remaining unaltered. Such disorder in cellulose was correlated with X-ray diffraction showing altered organization. Semi-quantitative immunolabeling of lignins showed that the patterns of distribution were differentially affected in interfascicular fibers and vascular bundles, pointing to the importance of noncondensed lignin structures for the assembly of a coherent secondary wall. The use of laser capture microdissection combined with the microanalysis of lignins and polysaccharides allowed these polymers to be characterized into specific cell types. Wild-type A. thaliana displayed a two-fold higher syringyl to guaiacyl ratio in interfascicular fibers compared with vascular bundles, whereas this difference was less marked in the cinnamoyl-CoA reductase 1 knockout mutant.

Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

NASA Astrophysics Data System (ADS)

Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

2004-04-01

To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

Microanalysis of plant cell wall polysaccharides.

PubMed

Obel, Nicolai; Erben, Veronika; Schwarz, Tatjana; Kühnel, Stefan; Fodor, Andrea; Pauly, Markus

2009-09-01

Oligosaccharide Mass Profiling (OLIMP) allows a fast and sensitive assessment of cell wall polymer structure when coupled with Matrix Assisted Laser Desorption Ionisation Time Of Flight Mass Spectrometry (MALDI-TOF MS). The short time required for sample preparation and analysis makes possible the study of a wide range of plant organs, revealing a high degree of heterogeneity in the substitution pattern of wall polymers such as the cross-linking glycan xyloglucan and the pectic polysaccharide homogalacturonan. The high sensitivity of MALDI-TOF allows the use of small amounts of samples, thus making it possible to investigate the wall structure of single cell types when material is collected by such methods as laser micro-dissection. As an example, the analysis of the xyloglucan structure in the leaf cell types outer epidermis layer, entire epidermis cell layer, palisade mesophyll cells, and vascular bundles were investigated. OLIMP is amenable to in situ wall analysis, where wall polymers are analyzed on unprepared plant tissue itself without first isolating cell walls. In addition, OLIMP enables analysis of wall polymers in Golgi-enriched fractions, the location of nascent matrix polysaccharide biosynthesis, enabling separation of the processes of wall biosynthesis versus post-deposition apoplastic metabolism. These new tools will make possible a semi-quantitative analysis of the cell wall at an unprecedented level.

Pulse wave velocity as a diagnostic index: The effect of wall thickness

NASA Astrophysics Data System (ADS)

Hodis, Simona

2018-06-01

Vascular compliance is a major determinant of wave propagation within the vascular system, and hence the measurement of pulse wave velocity (PWV) is commonly used clinically as a method of detecting vascular stiffening. The accuracy of that assessment is important because vascular stiffening is a major risk factor for hypertension. PWV is usually measured by timing a pressure wave as it travels from the carotid artery to the femoral or radial artery and estimating the distance that it traveled in each case to obtain the required velocity. A major assumption on which this technique is based is that the vessel wall thickness h is negligibly small compared with the vessel radius a . The extent to which this assumption is satisfied in the cardiovascular system is not known because the ratio h /a varies widely across different regions of the vascular tree and under different pathological conditions. Using the PWV as a diagnostic test without knowing the effect of wall thickness on the measurement could lead to error when interpreting the PWV value as an index of vessel wall compliance. The aim of the present study was to extend the validity of the current practice of assessing wall stiffness by developing a method of analysis that goes beyond the assumption of a thin wall. We analyzed PWVs calculated with different wall models, depending on the ratio of wall thickness to vessel radius and the results showed that PWV is not reliable when it is estimated with the classic thin wall theory if the vessel wall is not around 25% of vessel radius. If the arterial wall is thicker than 25% of vessel radius, then the wave velocity calculated with the thin wall theory could be overestimated and in the clinical setting, this could lead to a false positive. For thicker walls, a thick wall model presented here should be considered to account for the stresses within the wall thickness that become dominant compared with the wall inertia.

Measurement of vascular wall attenuation: comparison of CT angiography using model-based iterative reconstruction with standard filtered back-projection algorithm CT in vitro.

PubMed

Suzuki, Shigeru; Machida, Haruhiko; Tanaka, Isao; Ueno, Eiko

2012-11-01

To compare the performance of model-based iterative reconstruction (MBIR) with that of standard filtered back projection (FBP) for measuring vascular wall attenuation. After subjecting 9 vascular models (actual attenuation value of wall, 89 HU) with wall thickness of 0.5, 1.0, or 1.5 mm that we filled with contrast material of 275, 396, or 542 HU to scanning using 64-detector computed tomography (CT), we reconstructed images using MBIR and FBP (Bone, Detail kernels) and measured wall attenuation at the center of the wall for each model. We performed attenuation measurements for each model and additional supportive measurements by a differentiation curve. We analyzed statistics using analyzes of variance with repeated measures. Using the Bone kernel, standard deviation of the measurement exceeded 30 HU in most conditions. In measurements at the wall center, the attenuation values obtained using MBIR were comparable to or significantly closer to the actual wall attenuation than those acquired using Detail kernel. Using differentiation curves, we could measure attenuation for models with walls of 1.0- or 1.5-mm thickness using MBIR but only those of 1.5-mm thickness using Detail kernel. We detected no significant differences among the attenuation values of the vascular walls of either thickness (MBIR, P=0.1606) or among the 3 densities of intravascular contrast material (MBIR, P=0.8185; Detail kernel, P=0.0802). Compared with FBP, MBIR reduces both reconstruction blur and image noise simultaneously, facilitates recognition of vascular wall boundaries, and can improve accuracy in measuring wall attenuation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Suppressive effects of dietary EPA-rich fish oil on the degradation of elastin fibers in the aortic wall in nicotine-administered mice.

PubMed

Kugo, Hirona; Zaima, Nobuhiro; Onozato, Megumi; Miyamoto, Chie; Hashimoto, Keisuke; Yanagimoto, Kenichi; Moriyama, Tatsuya

2017-08-01

Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation of the abdominal aorta. Recent studies suggest that nicotine, which is a primary component in cigarette smoke, is closely associated with the development and rupture of an AAA. Nicotine accelerates AAA development through the weakening of the vascular wall by increasing oxidative stress and matrix metalloproteinase (MMP)-2 expression. However, little is known about preventing the AAA induced by nicotine. A non-surgical means of preventing the weakening of the vascular wall before the onset of AAA by functional food factors would be a valuable option over surgery. Fish oil is a functional food that is rich in n-3 polyunsaturated fatty acids that have an anti-inflammatory effect. In this study, we evaluated the effect of dietary fish oil on the weakening of the aortic wall due to nicotine administration in a mouse model. Histological analysis showed that the dietary fish oil suppressed the degradation of elastin fibers in the nicotine-administered mice. Additionally, the dietary fish oil suppressed the protein level of MMP-12, macrophage infiltration, and the oxidative stress in the vascular wall. These results suggest that fish oil could suppress the weakening of the vascular wall by suppressing the elastin fiber degradation caused by nicotine. By suppressing the nicotine induced weakening of the vascular wall, fish oil might help prevent the development of AAA.

[Aspects of vascular physiology in clinical and vascular surgical practice: basic principles of vascular mechanics].

PubMed

Nocke, H; Meyer, F; Lessmann, V

2014-10-01

To be able to evaluate properly a vascular problem, basic concepts of vascular physiology need to be considered, as they have been taught in physiology for a long time. This article deals with selected definitions and laws of passive vascular mechanics, subdivided into parameters of vascular filling and parameters of vascular flow. PARAMETERS OF VASCULAR FILLING: During vascular filling the transmural pressure distends the vascular wall until it is balanced by the wall tension. The extent of this distension up to the point of balance depends on the elasticity of the wall. Transmural pressure, wall tension and elasticity are defined, and their respective importance is described by clinical examples, e.g. aneurysm and varix. PARAMETERS OF VASCULAR FLOW: The vascular flow can be divided into stationary and pulsating components. Both components are relevant for the bloodstream. Since the blood flow is directed in the circuit, it can be understood in first approximation as stationary ("direct current").The direct current model uses only the average values of the pulsating variables. The great advantage of the direct current model is that it can be described with simple laws, which are not valid without reservation, but often allow a first theoretical approach to a vascular problem: Ohm's law, driving pressure, flow resistance, Hagen-Poiseuille law, wall shear stress, law of continuity, Bernoulli's equation and Reynold's number are described and associated with clinical examples.The heart is a pressure-suction pump and produces a pulsating flow, the pulse. The pulse runs with pulse wave velocity, which is much larger than the blood flow velocity, through the arterial vascular system. During propagation, the pulse has to overcome the wave resistance (impedance). Wherever the wave resistance changes, e.g., at vascular bifurcations and in the periphery, it comes to reflections. The incident (forward) and reflected (backward) waves are superimposed to yield the resulting pulse wave. This pulse wave allows one to distinguish pressure and flow pulse by measurement. Both are described separately, and their respective clinical meaning is illustrated by appropriate examples, e.g., arterial stiffness and pre-/postocclusive high/low resistance flow, respectively. Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of the significance of cell wall polymers in flax infected with a pathogenic strain of Fusarium oxysporum.

PubMed

Wojtasik, Wioleta; Kulma, Anna; Dymińska, Lucyna; Hanuza, Jerzy; Czemplik, Magdalena; Szopa, Jan

2016-03-22

Fusarium oxysporum infection leads to Fusarium-derived wilt, which is responsible for the greatest losses in flax (Linum usitatissimum) crop yield. Plants infected by Fusarium oxysporum show severe symptoms of dehydration due to the growth of the fungus in vascular tissues. As the disease develops, vascular browning and leaf yellowing can be observed. In the case of more virulent strains, plants die. The pathogen's attack starts with secretion of enzymes degrading the host cell wall. The main aim of the study was to evaluate the role of the cell wall polymers in the flax plant response to the infection in order to better understand the process of resistance and develop new ways to protect plants against infection. For this purpose, the expression of genes involved in cell wall polymer metabolism and corresponding polymer levels were investigated in flax seedlings after incubation with Fusarium oxysporum. This analysis was facilitated by selecting two groups of genes responding differently to the infection. The first group comprised genes strongly affected by the infection and activated later (phenylalanine ammonia lyase and glucosyltransferase). The second group comprised genes which are slightly affected (up to five times) and their expression vary as the infection progresses. Fusarium oxysporum infection did not affect the contents of cell wall polymers, but changed their structure. The results suggest that the role of the cell wall polymers in the plant response to Fusarium oxysporum infection is manifested through changes in expression of their genes and rearrangement of the cell wall polymers. Our studies provided new information about the role of cellulose and hemicelluloses in the infection process, the change of their structure and the expression of genes participating in their metabolism during the pathogen infection. We also confirmed the role of pectin and lignin in this process, indicating the major changes at the mRNA level of lignin metabolism genes and the loosening of the pectin structure.

Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

PubMed

Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

2018-01-15

Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison of acellular dermal matrix and synthetic mesh for lateral chest wall reconstruction in a rabbit model.

PubMed

Holton, Luther H; Chung, Thomas; Silverman, Ronald P; Haerian, Hafez; Goldberg, Nelson H; Burrows, Whitney M; Gobin, Andrea; Butler, Charles E

2007-04-01

Synthetic mesh is used for chest wall reconstruction, but infection or exposure can occur and necessitate removal. Human acellular dermal matrix (AlloDerm) has been used to reconstruct musculofascial defects in the trunk with low infection and herniation rates. AlloDerm may have advantages over synthetic mesh for chest wall reconstruction. This study compared outcomes and repair strengths of AlloDerm to expanded polytetrafluoroethylene mesh used for repair of rib cage defects. A 3 x 3-cm, full-thickness, lateral rib cage defect was created in each rabbit and repaired with expanded polytetrafluoroethylene (n = 8) or acellular dermal matrix (n = 9). At 4 weeks, the animals were euthanized and evaluated for lung herniation/dehiscence, strength of adhesions between the implant and intrapleural structures, and breaking strength of the implant materials and the implant-fascia interface. Tissue sections were analyzed with histologic and immunohistochemical staining to evaluate cellular infiltration and vascularization. No herniation or dehiscence occurred with either material. The incidence and strength of adhesions was similar between materials. The mean breaking strength of the AlloDerm-fascia interface (14.5 +/- 8.9 N) was greater than the expanded polytetrafluoroethylene-fascia interface (8.7 +/- 4.4 N; p = 0.027) and similar to the rib-intercostal-rib interface of the contralateral native chest wall (14.0 +/- 5.6 N). The AlloDerm grafts became infiltrated with cells and vascularized after implantation. AlloDerm used for chest wall reconstruction results in greater implant-defect interface strength than expanded polytetrafluoroethylene. The ability of AlloDerm to become vascularized and remodeled by autologous cells and to resist infection may be advantageous for chest wall reconstruction.

Numerical Simulation of the Flow in Vascular Grafts for Surgical Applications

NASA Astrophysics Data System (ADS)

McGah, Patrick; Aliseda, Alberto

2009-11-01

Numerical simulation of the human blood vessels, is becoming an important tool in surgical planning and research. Accurate vascular simulations might grant physicians the predictive capability to perform pre-surgical planning. We focus our attention on the implantation of vascular grafts. The high rate of failure of this common vascular interaction is intimately related to the fluid mechanics in the affected region and the subsequent wall tissue remodeling. Here, we will present our current work in developing a methodology for the numerical simulation of vascular grafts which incorporates physiologically realistic geometries and flow boundary conditions. In particular, we seek to correlate the wall shear stress and its spatial (WSSG) and temporal (OSI) variability to wall remodeling as observed in patient specific longitudinal studies. The pulsatility (Remean= 800 , Repeak= 2000, Wo = 2) of the flow gives rise to additional fluid dynamics phenomena such as instability, flow separation, transition, and unsteadiness. Our goal is to describe and evaluate their effect on the wall physiology.

Lipidomics in vascular health: current perspectives.

PubMed

Kolovou, Genovefa; Kolovou, Vana; Mavrogeni, Sophie

2015-01-01

Identifying the mechanisms that convert a healthy vascular wall to an atherosclerotic wall is of major importance since the consequences may lead to a shortened lifespan. Classical risk factors (age, smoking, obesity, diabetes mellitus, hypertension, and dyslipidemia) may result in the progression of atherosclerotic lesions by processes including inflammation and lipid accumulation. Thus, the evaluation of blood lipids and the full lipid complement produced by cells, organisms, or tissues (lipidomics) is an issue of importance. In this review, we shall describe the recent progress in vascular health research using lipidomic advances. We will begin with an overview of vascular wall biology and lipids, followed by a short analysis of lipidomics. Finally, we shall focus on the clinical implications of lipidomics and studies that have examined lipidomic approaches and vascular health.

Retinal Arterioles in Hypo-, Normo-, and Hypertensive Subjects Measured Using Adaptive Optics.

PubMed

Hillard, Jacob G; Gast, Thomas J; Chui, Toco Y P; Sapir, Dan; Burns, Stephen A

2016-08-01

Small artery and arteriolar walls thicken due to elevated blood pressure. Vascular wall thickness show a correlation with hypertensive subject history and risk for stroke and cardiovascular events. The inner and outer diameter of retinal arterioles from less than 10 to over 150 μm were measured using a multiply scattered light adaptive optics scanning laser ophthalmoscope (AOSLO). These measurements were made on three populations, one with habitual blood pressures less than 100/70 mm Hg, one with normal blood pressures without medication, and one with managed essential hypertension. The wall to lumen ratio was largest for the smallest arterioles for all three populations. Data from the hypotensive group had a linear relationship between outer and inner diameters ( r 2 = 0.99) suggesting a similar wall structure in individuals prior to elevated blood pressures. Hypertensive subjects fell below the 95% confidence limits for the hypotensive relationship and had larger wall to lumen ratios and the normotensive group results fell between the other two groups. High-resolution retinal imaging of subjects with essential hypertension showed a significant decrease in vessel inner diameter for a given outer diameter, and increases in wall to lumen ratio and wall cross-sectional areas over the entire range of vessel diameters and suggests that correcting for vessel size may improve the ability to identify significant vascular changes. High-resolution imaging allows precise measurement of vasculature and by comparing results across risk populations may allow improved identification of individuals undergoing hypertensive arterial wall remodeling.

Something more to say about calcium homeostasis: the role of vitamin K2 in vascular calcification and osteoporosis.

PubMed

Flore, R; Ponziani, F R; Di Rienzo, T A; Zocco, M A; Flex, A; Gerardino, L; Lupascu, A; Santoro, L; Santoliquido, A; Di Stasio, E; Chierici, E; Lanti, A; Tondi, P; Gasbarrini, A

2013-09-01

Vascular calcification and osteoporosis share similar etiopathogenetic mechanisms. Vitamin K2 deficiency could be responsible of the so called "calcium paradox", that is the lack of calcium in the bone and its storage in the vessel wall. These events may have clinically relevant consequences, such as cardiovascular accidents, and bone fractures. To review the biological function of vitamin K2 metabolism, the main factors related to its deficiency and the consequent clinical significance. Vitamin K2 is essential for the function of several proteins, involved in the maintenance of the normal structure of arterial wall, osteoarticular system, teeth, and for the regulation of cell growth. It has been demonstrated to have a pivotal role in the inhibition of vascular foci of calcification, and in the regulation of calcium deposition in the bone. Vitamin K2 deficiency is often subclinic in a large part of healthy population. This deficiency is related to the interaction of various factors, such as the reduced dietary intake, the alteration of intestinal absorption or production, with a possible role of intestinal microbiota and the increased consumption at the vessel wall. Vitamin K2 deficiency has recently been recognized as a protagonist in the development of vascular calcification and osteoporosis. Data reported so far are promising and, dietary supplementation seems a useful tool to contrast these diseases. However, large studies or solid clinical correlations regarding vitamin K2 deficiency and its pathologic consequences are needed to confirm these preliminary experiences.

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats.

PubMed

Brooks, Steven D; DeVallance, Evan; d'Audiffret, Alexandre C; Frisbee, Stephanie J; Tabone, Lawrence E; Shrader, Carl D; Frisbee, Jefferson C; Chantler, Paul D

2015-12-01

The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7-8, 12-13, and 16-17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7-8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS. Copyright © 2015 the American Physiological Society.

Direct Leukocyte Migration across Pulmonary Arterioles and Venules into the Perivascular Interstitium of Murine Lungs during Bleomycin Injury and Repair

PubMed Central

Wang, Ping M.; Kachel, Diane L.; Cesta, Mark F.; Martin, William J.

2011-01-01

During acute lung injury and repair, leukocytes are thought to enter the lung primarily across alveolar capillaries and postcapillary venules. We hypothesized that leukocytes also migrate across pulmonary arterioles and venules, which serve as alternative sites for leukocyte influx into the lung during acute lung injury and repair. Lung sections from C57BL/6J mice up to 14 days after intratracheal bleomycin (3.33 U/kg) or saline instillation were assessed by light, fluorescence, confocal, and transmission electron microscopy for evidence of inflammatory cell sequestration and transmigration at these sites. After bleomycin treatment, large numbers of leukocytes (including neutrophils, eosinophils, and monocytes) were present in the vascular lumina and in perivascular interstitia of pulmonary arterioles and venules, as well as within the vascular walls. Leukocytes were observed within well-defined pathways in arteriolar walls and much less structured pathways in venular walls, apparently in the process of transmigration. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were expressed at sites of leukocyte interaction with the luminal surface, especially in arterioles. Leukocytes appeared to exit from the vessels near collagen fibers into the perivascular interstitium. Results indicate that leukocytes can directly migrate across arteriolar and venular walls into the perivascular interstitium, which may represent an important but under-recognized pathway for leukocyte influx into the lung during injury and repair. PMID:21641381

Cellular origin of fibronectin in interspecies hybrid kidneys

PubMed Central

1984-01-01

The cellular origin of fibronectin in the kidney was studied in three experimental models. Immunohistochemical techniques that use cross- reacting or species-specific antibodies against mouse or chicken fibronectin were employed. In the first model studied, initially avascular mouse kidneys cultured on avian chorioallantoic membranes differentiate into epithelial kidney tubules and become vascularized by chorioallantoic vessels. Subsequently, hybrid glomeruli composed of mouse podocytes and avian endothelial-mesangial cells form. In immunohistochemical studies, cross-reacting antibodies to fibronectin stained vascular walls, tubular basement membranes, interstitium, and glomeruli of mouse kidney grafts. The species-specific antibodies reacting only with mouse fibronectin stained interstitial areas and tubular basement membranes, but showed no reaction with hybrid glomeruli and avian vascular walls. In contrast, species-specific antibodies against chicken fibronectin stained both the interstitial areas and the vascular walls as well as the endothelial-mesangial areas of the hybrid glomeruli, but did not stain the mouse-derived epithelial structures of the kidneys. In the second model, embryonic kidneys cultured under avascular conditions in vitro develop glomerular tufts, which are devoid of endothelial cells. These explants showed fluorescence staining for fibronectin only in tubular basement membranes and in interstitium. The avascular, purely epithelial glomerular bodies remained unstained. Finally, in outgrowths of separated embryonic glomeruli, the cross-reacting fibronectin antibodies revealed two populations of cells: one devoid of fibronectin and another expressing fibronectin in strong fibrillar and granular patterns. These results favor the idea that the main endogenous cellular sources for fibronectin in the embryonic kidney are the interstitial and vascular cells. All experiments presented here suggest that fibronectin is not synthesized by glomerular epithelial cells in vivo. PMID:6389571

Structural remodeling of coronary resistance arteries: effects of age and exercise training

PubMed Central

Hanna, Mina A.; Taylor, Curtis R.; Chen, Bei; La, Hae-Sun; Maraj, Joshua J.; Kilar, Cody R.; Behnke, Bradley J.; Delp, Michael D.

2014-01-01

Age is known to induce remodeling and stiffening of large-conduit arteries; however, little is known of the effects of age on remodeling and mechanical properties of coronary resistance arteries. We employed a rat model of aging to investigate whether 1) age increases wall thickness and stiffness of coronary resistance arteries, and 2) exercise training reverses putative age-induced increases in wall thickness and stiffness of coronary resistance arteries. Young (4 mo) and old (21 mo) Fischer 344 rats remained sedentary or underwent 10 wk of treadmill exercise training. Coronary resistance arteries were isolated for determination of wall-to-lumen ratio, effective elastic modulus, and active and passive responses to changes in intraluminal pressure. Elastin and collagen content of the vascular wall were assessed histologically. Wall-to-lumen ratio increased with age, but this increase was reversed by exercise training. In contrast, age reduced stiffness, and exercise training increased stiffness in coronary resistance arteries from old rats. Myogenic responsiveness was reduced with age and restored by exercise training. Collagen-to-elastin ratio (C/E) of the wall did not change with age and was reduced with exercise training in arteries from old rats. Thus age induces hypertrophic remodeling of the vessel wall and reduces the stiffness and myogenic function of coronary resistance arteries. Exercise training reduces wall-to-lumen ratio, increases wall stiffness, and restores myogenic function in aged coronary resistance arteries. The restorative effect of exercise training on myogenic function of coronary resistance arteries may be due to both changes in vascular smooth muscle phenotype and expression of extracellular matrix proteins. PMID:25059239

Site-specific association between distal aortic pulse wave velocity and peripheral arterial stenosis severity: a prospective cardiovascular magnetic resonance study.

PubMed

van den Bosch, Harrie C M; Westenberg, Jos J M; Setz-Pels, Wikke; Wondergem, John; Wolterbeek, Ron; Duijm, Lucien E M; Teijink, Joep A W; de Roos, Albert

2015-01-20

Vascular disease expression in one location may not be representative for disease severity in other vascular territories, however, strong correlation between disease expression and severity within the same vascular segment may be expected. Therefore, we hypothesized that aortic stiffening is more strongly associated with disease expression in a vascular territory directly linked to that aortic segment rather than in a more remote segment. We prospectively compared the association between aortic wall stiffness, expressed by pulse wave velocity (PWV), sampled in the distal aorta, with the severity of peripheral arterial occlusive disease (PAOD) as compared to atherosclerotic markers sampled in remote vascular territories such as PWV in the proximal aorta and the normalized wall index (NWI), representing the vessel wall thickness, of the left common carotid artery. Forty-two patients (23 men; mean age 64±10 years) underwent velocity-encoded cardiovascular magnetic resonance (CMR) in the proximal and distal aorta, whole-body contrast-enhanced MR angiography (CE-MRA) and carotid vessel wall imaging with black-blood CMR in the work-up for PAOD. Strength of associations between aortic stiffness, carotid NWI and peripheral vascular stenosis grade were assessed and evaluated with multiple linear regression. Stenosis severity correlated well with PWV in the distal aorta (Pearson rP=0.64, p<0.001, Spearman rS=0.65, p<0.001) but to a lesser extent with PWV in the proximal aorta (rP=0.48, p=0.002, rS=0.22, p=0.18). Carotid NWI was not associated with peripheral stenosis severity (rP=0.17, p=0.28, rS=0.14, p=0.37) nor with PWV in the proximal aorta (rP=0.22, p=0.17) nor in the distal aorta (rP=0.21, p=0.18). Correlation between stenosis severity and distal aortic PWV remained statistically significant after correction for age and gender. Distal aortic wall stiffness is more directly related to peripheral arterial stenosis severity than markers from more remote vascular territories such as proximal aortic wall stiffness or carotid arterial wall thickness. Site-specific evaluation of vascular disease may be required for full vascular risk estimation.

3',5'-cIMP as Potential Second Messenger in the Vascular Wall.

PubMed

Leung, Susan W S; Gao, Yuansheng; Vanhoutte, Paul M

2017-01-01

Traditionally, only the 3',5'-cyclic monophosphates of adenosine and guanosine (produced by adenylyl cyclase and guanylyl cyclase, respectively) are regarded as true "second messengers" in the vascular wall, despite the presence of other cyclic nucleotides in different tissues. Among these noncanonical cyclic nucleotides, inosine 3',5'-cyclic monophosphate (cIMP) is synthesized by soluble guanylyl cyclase in porcine coronary arteries in response to hypoxia, when the enzyme is activated by endothelium-derived nitric oxide. Its production is associated with augmentation of vascular contraction mediated by stimulation of Rho kinase. Based on these findings, cIMP appears to meet most, if not all, of the criteria required for it to be accepted as a "second messenger," at least in the vascular wall.

A computer simulation of the plasma leakage through a vascular prosthesis made of expanded polytetrafluoroethylene.

PubMed

Tabata, R; Kobayashi, T; Mori, A; Matsuno, S; Watarida, S; Onoe, M; Sugita, T; Shiraisi, S; Nojima, T

1993-04-01

We explored the blood-retaining mechanism of a vascular prosthesis made of expanded polytetrafluoroethylene through analysis of its structure and physicochemical properties. Plasma leakage through this vascular prosthesis was simulated by computer to explore its etiology. These examinations disclosed that leakage is dependent upon the inner pressure and the density of fibers. In other words, the study revealed that the mean distance between fibers constituting the wall of the expanded polytetrafluoroethylene vascular prosthesis is increased by tension (that is, inner pressure), resulting in an increased probability of leakage. It was additionally found that a thin membrane is formed on the polytetrafluoroethylene surface if blood in contact with the surface is dried. This membrane was found to reduce the water-repelling property of polytetrafluoroethylene and to make it impossible to preserve the inter-fiber liquid surface, thus causing leakage through the expanded polytetrafluoroethylene vascular prosthesis.

The angiotensin receptor blocker losartan reduces coronary arteriole remodeling in type 2 diabetic mice

PubMed Central

Husarek, Kathryn E.; Katz, Paige S.; Trask, Aaron J.; Galantowicz, Maarten L.; Cismowski, Mary J.; Lucchesi, Pamela A.

2017-01-01

Cardiovascular complications are a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM) and are associated with alterations of blood vessel structure and function. Although endothelial dysfunction and aortic stiffness have been documented, little is known about the effects of T2DM on coronary microvascular structural remodeling. The renin–angiotensin–aldosterone system plays an important role in large artery stiffness and mesenteric vessel remodeling in hypertension and T2DM. The goal of this study was to determine whether the blockade of AT1R signaling dictates vascular smooth muscle growth that partially underlies coronary arteriole remodeling in T2DM. Control and db/db mice were given AT1R blocker losartan via drinking water for 4 weeks. Using pressure myography, we found that coronary arterioles from 16-week db/db mice undergo inward hypertrophic remodeling due to increased wall thickness and wall-to-lumen ratio with a decreased lumen diameter. This remodeling was accompanied by decreased elastic modulus (decreased stiffness). Losartan treatment decreased wall thickness, wall-to-lumen ratio, and coronary arteriole cell number in db/db mice. Losartan treatment did not affect incremental elastic modulus. However, losartan improved coronary flow reserve. Our data suggest that Ang II–AT1R signaling mediates, at least in part, coronary arteriole inward hypertrophic remodeling in T2DM without affecting vascular mechanics, further suggesting that targeting the coronary microvasculature in T2DM may help reduce cardiac ischemic events. PMID:26133668

Patient-Specific Simulations of Reactivity in Models of the Pulmonary Vasculature: A 3-D Numerical Study with Fluid-Structure Interaction

NASA Astrophysics Data System (ADS)

Hunter, Kendall; Zhang, Yanhang; Lanning, Craig

2005-11-01

Insight into the progression of pulmonary hypertension may be obtained from thorough study of vascular flow during reactivity testing, an invasive diagnostic procedure which can dramatically alter vascular hemodynamics. Diagnostic imaging methods, however, are limited in their ability to provide extensive data. Here we present detailed flow and wall deformation results from simulations of pulmonary arteries undergoing this procedure. Patient-specific 3-D geometric reconstructions of the first four branches of the pulmonary vasculature were obtained clinically and meshed for use with computational software. Transient simulations in normal and reactive states were obtained from four such models were completed with patient-specific velocity inlet conditions and flow impedance exit conditions. A microstructurally based orthotropic hyperelastic model that simulates pulmonary artery mechanics under normotensive and hypoxic hypertensive conditions treated wall constitutive changes due to pressure reactivity and arterial remodeling. Pressure gradients, velocity fields, arterial deformation, and complete topography of shear stress were obtained. These models provide richer detail of hemodynamics than can be obtained from current imaging techniques, and should allow maximum characterization of vascular function in the clinical situation.

Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction.

PubMed

Yannoutsos, Alexandra; Levy, Bernard I; Safar, Michel E; Slama, Gerard; Blacher, Jacques

2014-02-01

Hypertension is a multifactorial systemic chronic disorder through functional and structural macrovascular and microvascular alterations. Macrovascular alterations are featured by arterial stiffening, disturbed wave reflection and altered central to peripheral pulse pressure amplification. Microvascular alterations, including altered wall-to-lumen ratio of larger arterioles, vasomotor tone abnormalities and network rarefaction, lead to disturbed tissue perfusion and susceptibility to ischemia. Central arterial stiffness and microvascular alterations are common denominators of organ damages. Vascular alterations are intercorrelated, amplifying the haemodynamic load and causing further damage in the arterial network. A plausible precursor role of vascular alterations in incident hypertension provides new insights for preventive and therapeutic strategies targeting macro and microvasculature. Cumulative metabolic burden and oxidative stress lead to chronic endothelial injury, promoting structural and functional vascular alterations, especially in the microvascular network. Pathophysiology of hypertension may then be revisited, based on both macrovascular and microvascular alterations, with a precursor role of endothelial dysfunction for the latter.

Pathophysiology of the vascular wall and its relevance for cerebrovascular disorders in aged rodents.

PubMed

Popa-Wagner, A; Pirici, D; Petcu, E B; Mogoanta, L; Buga, A-M; Rosen, C L; Leon, R; Huber, J

2010-08-01

Chronic hypertension and cerebral amyloid angiopathy (CAA) are the main pathologies which can induce the rupture of cerebral vessels and intracerebral hemorrhages, as a result of degenerative changes in the vascular wall. A lot of progress has been made in this direction since the successful creation of the first mouse model for the study of Alzheimer's disease (AD), as the spectrum of AD pathology includes a plethora of changes found in pure cerebrovascular diseases. We describe here some of these mouse models having important vascular changes that parallel human AD pathology, and more importantly, we show how these models have helped us understand more about the mechanisms that lead to CAA formation. An important cellular event associated with reduced structural and functional recovery after stroke in aged animals is the early formation of a scar in the infarcted region that impairs subsequent neural recovery and repair. We review recent evidence showing that the rapid formation of the glial scar following stroke in aged rats is associated with premature cellular proliferation that originates primarily from the walls of capillaries in the corpus callosum adjacent to the infarcted region. After stroke several vascular mechanisms are turned-on immediately to protect the brain from further damage and help subsequent neuroregeneration and functional recovery. Although does occur after stroke, vasculogenesis is overshadowed in its protective/restorative role by the angiogenesis and arteriogenesis. Understanding the basic mechanisms underlying functional recovery after cerebral stroke in aging subjects is likely to yield new insights into the treatment of brain injury in the clinic.

Predicting the size-dependent tissue accumulation of agents released from vascular targeted nanoconstructs

NASA Astrophysics Data System (ADS)

de Tullio, Marco D.; Singh, Jaykrishna; Pascazio, Giuseppe; Decuzzi, Paolo

2014-03-01

Vascular targeted nanoparticles have been developed for the delivery of therapeutic and imaging agents in cancer and cardiovascular diseases. However, at authors' knowledge, a comprehensive systematic analysis on their delivery efficiency is still missing. Here, a computational model is developed to predict the vessel wall accumulation of agents released from vascular targeted nanoconstructs. The transport problem for the released agent is solved using a finite volume scheme in terms of three governing parameters: the local wall shear rate , ranging from to ; the wall filtration velocity , varying from to ; and the agent diffusion coefficient , ranging from to . It is shown that the percentage of released agent adsorbing on the vessel walls in the vicinity of the vascular targeted nanoconstructs reduces with an increase in shear rate , and with a decrease in filtration velocity and agent diffusivity . In particular, in tumor microvessels, characterized by lower shear rates () and higher filtration velocities (), an agent with a diffusivity (i.e. a 50 nm particle) is predicted to deposit on the vessel wall up to of the total released dose. Differently, drug molecules, exhibiting a smaller size and much higher diffusion coefficient (), are predicted to accumulate up to . In healthy vessels, characterized by higher and lower , the largest majority of the released agent is redistributed directly in the circulation. These data suggest that drug molecules and small nanoparticles only can be efficiently released from vascular targeted nanoconstructs towards the diseased vessel walls and tissue.

Cloacal morphology of Nothura maculosa (Temminck, 1815), Aves tinamiformes.

PubMed

de Oliveira, C A; Mahecha, G A

1996-10-01

Cloacae of male Nothura maculosa (spotted tinamous) were dissected and studied with routine histological and histochemical techniques. In the cloaca of this species the following cranio-caudally oriented regions can be recognized: the coprodeum, the urodeum and the proctodeum, separated by the coprourodeal and the uroproctodeal folds respectively. The coprodeum is an abrupt dilatation of the rectum which receives the ureters, contrary to other birds in which they open into the urodeum. The urodeum is the smallest compartment of the cloaca. Its wall presents the paracloacal vascular bodies and the ductus deferens receptacles which open into the ejaculatory fossa through a pair of papillae. The ejaculatory fossa forms the ventral floor of the urodeum and is characterized by the presence of a secretory epithelium and a lamina propria showing rich vascularization. The proctodeum is connected to the exterior through the cloacal opening and ventrally it presents the phallic structures and the proctodeal lamella. Its dorsolateral wall forms the cloacal bursa, its mucosa shows morphological variations depending on the degree of regression. Enclosing the uroproctodeal wall are the cloacal sphincter muscle and the skin.

Apolipoprotein B, the villain in the drama?

PubMed

Yu, Qi; Zhang, Yaping; Xu, Cang-Bao

2015-02-05

Low-density lipoprotein (LDL) is the major atherogenic lipoprotein and the primary target of lipid-lowering therapy for treating ischemic cardiovascular disease. Apolipoprotein B (apoB), an important structural component of LDL, plays a key role in cholesterol transport and removal in vascular wall. On the other hand, under pathological process, apoB interacts with the arterial wall to initiate the cascade of events that leads to atherosclerosis. However, interactions between apoB and vascular wall remain to be determined. Here, we address a pathological role of apoB per se and whole LDL particle in dysfunction of vascular endothelium and smooth muscle cells i.e. decreased endothelium-dependent vasodilation and increased receptor-mediated vasoconstriction. We intend to discuss: i) how apoB is responsible for the deleterious effects of LDL in the development of ischemic cardiovascular disease; ii) why vaccine based on peptides derived from apoB-100 is a promising therapy for treating ischemic cardiovascular disease, and iii) direct inhibition of apoB production should be a better therapeutic option than simple LDL-cholesterol lowering therapy in the patients with severe hypercholesterolemia at high cardiovascular risk with statin intolerance. In conclusion, apoB, but not cholesterol, plays a major role in LDL-induced dysfunction of endothelium, suggesting that direct apoB-targeting agents might be a promising therapy for the treatment of ischemic cardiovascular disease. Copyright © 2014 Elsevier B.V. All rights reserved.

[Anomalous systemic arterial supply to normal basal segments of the left lung (Pryce type I)].

PubMed

Ryu, Chusei; Sawada, Takahiro; Machino, Ryusuke

2013-03-01

Patient 1 was a 54-year-old female diagnosed with anomalous systemic arterial supply to normal basal segments of the left lung discovered as an abnormality on chest X-ray radiography. Patient 2 was a 47-year-old male in whom the disease was diagnosed by close examination of bloody sputum. Division of the abnormal artery and left lower lobectomy were performed in patient 1. Arterial congestion and serpentine distribution were noted in the basal segments of the lung, which was the region perfused by the abnormal artery, on histopathological examination. Arteriosclerotic changes were noted in the vascular wall, but no abnormal vascular wall or alveolar structure was noted in S6, which was not included in theperfused region. Based on the above findings, division of the abnormal artery and left basal segmentectomy were performed in patient 2. Bloody sputum disappeared, and activity of daily living( ADL) were not impaired after surgery.

Retroperitoneal and rectus sheath hematomas.

PubMed

Kasotakis, George

2014-02-01

The retroperitoneum is rich in vascular structures and can harbor large hematomas, traumatic or spontaneous. The management of retroperitoneal hematomas depends on the mechanism of injury and whether they are pulsatile/expanding. Rectus sheath hematomas are uncommon abdominal wall hematomas secondary to trauma to the epigastric arteries of the rectus muscle. The common risk factors include anticoagulation, strenuous exercise, coughing, coagulation disorders, and invasive procedures on/through the abdominal wall. The management is largely supportive, with the reversal of anticoagulation and transfusions; angioembolization may be necessary. Copyright © 2014 Elsevier Inc. All rights reserved.

Hedgehog and Resident Vascular Stem Cell Fate

PubMed Central

Mooney, Ciaran J.; Hakimjavadi, Roya; Fitzpatrick, Emma; Kennedy, Eimear; Walls, Dermot; Morrow, David; Redmond, Eileen M.; Cahill, Paul A.

2015-01-01

The Hedgehog pathway is a pivotal morphogenic driver during embryonic development and a key regulator of adult stem cell self-renewal. The discovery of resident multipotent vascular stem cells and adventitial progenitors within the vessel wall has transformed our understanding of the origin of medial and neointimal vascular smooth muscle cells (SMCs) during vessel repair in response to injury, lesion formation, and overall disease progression. This review highlights the importance of components of the Hh and Notch signalling pathways within the medial and adventitial regions of adult vessels, their recapitulation following vascular injury and disease progression, and their putative role in the maintenance and differentiation of resident vascular stem cells to vascular lineages from discrete niches within the vessel wall. PMID:26064136

Device and method for treatment of openings in vascular and septal walls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singhal, Pooja; Wilson, Thomas S.; Cosgriff-Hernandez, Elizabeth

A device, system and method for treatment of an opening in vascular and/or septal walls including patent foramen ovale. The device has wings/stops on either end, an axis core covered in a shape memory foam and is deliverable via a catheter to the affected opening, finally expanding into a vascular or septal opening where it is held in place by the expandable shape memory stops or wings.

In Vivo Evaluation of Short-Term Performance of New Three-Layer Collagen-Based Vascular Graft Designed for Low-Flow Peripheral Vascular Reconstructions

PubMed Central

Grus, Tomas; Mlcek, Mikulas; Chlup, Hynek; Honsova, Eva; Spacek, Miroslav; Burgetova, Andrea; Lindner, Jaroslav

2018-01-01

Aim The aim of this study was to evaluate short-term patency of the new prosthetic graft and its structural changes after explantation. Methods The study team developed a three-layer conduit composed of a scaffold made from polyester coated with collagen from the inner and outer side with an internal diameter of 6 mm. The conduit was implanted as a bilateral bypass to the carotid artery in 7 sheep and stenosis was created in selected animals. After a period of 161 days, the explants were evaluated as gross and microscopic specimens. Results The initial flow rate (median ± IQR) in grafts with and without artificial stenosis was 120 ± 79 ml/min and 255 ± 255 ml/min, respectively. Graft occlusion occurred after 99 days in one of 13 conduits (patency rate: 92%). Wall-adherent thrombi occurred only in sharp curvatures in two grafts. Microscopic evaluation showed good engraftment and preserved structure in seven conduits; inflammatory changes with foci of bleeding, necrosis, and disintegration in four conduits; and narrowing of the graft due to thickening of the wall with multifocal separation of the outer layer in two conduits. Conclusions This study demonstrates good short-term patency rates of a newly designed three-layer vascular graft even in low-flow conditions in a sheep model. PMID:29682536

In Vivo Evaluation of Short-Term Performance of New Three-Layer Collagen-Based Vascular Graft Designed for Low-Flow Peripheral Vascular Reconstructions.

PubMed

Grus, Tomas; Lambert, Lukas; Mlcek, Mikulas; Chlup, Hynek; Honsova, Eva; Spacek, Miroslav; Burgetova, Andrea; Lindner, Jaroslav

2018-01-01

The aim of this study was to evaluate short-term patency of the new prosthetic graft and its structural changes after explantation. The study team developed a three-layer conduit composed of a scaffold made from polyester coated with collagen from the inner and outer side with an internal diameter of 6 mm. The conduit was implanted as a bilateral bypass to the carotid artery in 7 sheep and stenosis was created in selected animals. After a period of 161 days, the explants were evaluated as gross and microscopic specimens. The initial flow rate (median ± IQR) in grafts with and without artificial stenosis was 120 ± 79 ml/min and 255 ± 255 ml/min, respectively. Graft occlusion occurred after 99 days in one of 13 conduits (patency rate: 92%). Wall-adherent thrombi occurred only in sharp curvatures in two grafts. Microscopic evaluation showed good engraftment and preserved structure in seven conduits; inflammatory changes with foci of bleeding, necrosis, and disintegration in four conduits; and narrowing of the graft due to thickening of the wall with multifocal separation of the outer layer in two conduits. This study demonstrates good short-term patency rates of a newly designed three-layer vascular graft even in low-flow conditions in a sheep model.

Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension

PubMed Central

Roque, Fernanda R; Briones, Ana M; García-Redondo, Ana B; Galán, María; Martínez-Revelles, Sonia; Avendaño, Maria S; Cachofeiro, Victoria; Fernandes, Tiago; Vassallo, Dalton V; Oliveira, Edilamar M; Salaices, Mercedes

2013-01-01

Background and Purpose Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (SHR). Experimental Approach Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks were used to evaluate vascular structural, mechanical and functional properties. Key Results Exercise did not affect lumen diameter, wall thickness and wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric arteries from SHR. Exercise also reduced collagen deposition and normalized altered internal elastic lamina organization and expression of MMP-9 in mesenteric arteries from SHR. Exercise did not affect contractile responses of coronary arteries but improved the endothelium-dependent relaxation in SHR. In mesenteric arteries, training normalized the increased contractile responses induced by U46619 and by high concentrations of acetylcholine. In vessels from SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized the increased O2− production and the reduced Cu/Zn superoxide dismutase expression and increased NO production. Conclusions and Implications Exercise training of SHR improves endothelial function and vascular stiffness in coronary and small mesenteric arteries. This might be related to the concomitant decrease of oxidative stress and increase of NO bioavailability. Such effects demonstrate the beneficial effects of exercise on the vascular system and could contribute to a reduction in blood pressure. PMID:22994554

Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension.

PubMed

Roque, Fernanda R; Briones, Ana M; García-Redondo, Ana B; Galán, María; Martínez-Revelles, Sonia; Avendaño, Maria S; Cachofeiro, Victoria; Fernandes, Tiago; Vassallo, Dalton V; Oliveira, Edilamar M; Salaices, Mercedes

2013-02-01

Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (SHR). Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks were used to evaluate vascular structural, mechanical and functional properties. Exercise did not affect lumen diameter, wall thickness and wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric arteries from SHR. Exercise also reduced collagen deposition and normalized altered internal elastic lamina organization and expression of MMP-9 in mesenteric arteries from SHR. Exercise did not affect contractile responses of coronary arteries but improved the endothelium-dependent relaxation in SHR. In mesenteric arteries, training normalized the increased contractile responses induced by U46619 and by high concentrations of acetylcholine. In vessels from SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized the increased O(2) (-) production and the reduced Cu/Zn superoxide dismutase expression and increased NO production. Exercise training of SHR improves endothelial function and vascular stiffness in coronary and small mesenteric arteries. This might be related to the concomitant decrease of oxidative stress and increase of NO bioavailability. Such effects demonstrate the beneficial effects of exercise on the vascular system and could contribute to a reduction in blood pressure. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Interaction of Vascular Smooth Muscle Cells Under Low Shear Stress

NASA Technical Reports Server (NTRS)

Seidel, Charles L.

1998-01-01

The blood vessel wall consists of three cellular layers, an outer adventitial, a middle medial and an inner intimal layer. When the blood vessel forms in the embryo it begins as a tube composed of a single cell type called endothelial cells. Over time, other cells are recruited from the surrounding tissue to form additional layers on the outer surface of the endothelial tube. The cells that are recruited are called mesenchymal cells. Mesenchymal cells are responsible for the production of connective tissue that holds the blood vessel together and for developing into vascular smooth muscle cells that are responsible for regulating the diameter of the vessel (1) and therefore, blood flow. In a fully developed blood vessel, the endothelial cells make- up the majority of cells in the intimal layer while the mesenchymal cells make-up the majority of cells in the medial and adventitial layers. Within the medial layer of a mature vessel, cells are organized into multiple circular layers of alternating bands of connective tissue and cells. The cell layer is composed of a mixture of mesenchymal cells that have not developed into smooth muscle cells and fully developed smooth muscle cells (2). The assembly and organization of complex tissues is directed in part by a signaling system composed of proteins on the cell surface called adhesion molecules. Adhesion molecules enable cells to recognize each other as well as the composition of the connective tissue in which they reside (3). It was hypothesized that the different cell types that compose the vascular wall possess different adhesion molecules that enable them to recognize each other and through this recognition system, form the complex layered organization of the vascular wall. In other words, the layered organization is an intrinsic property of the cells. If this hypothesis is correct then the different cells that make up the vessel wall, when mixed together, should organize themselves into a layered structure resembling an intact blood vessel. Experiments described below were designed to test this hypothesis.

Arterial stiffness estimation based photoplethysmographic pulse wave analysis

NASA Astrophysics Data System (ADS)

Huotari, Matti; Maatta, Kari; Kostamovaara, Juha

2010-11-01

Arterial stiffness is one of the indices of vascular healthiness. It is based on pulse wave analysis. In the case we decompose the pulse waveform for the estimation and determination of arterial elasticity. Firstly, optically measured with photoplethysmograph and then investigating means by four lognormal pulse waveforms for which we can find very good fit between the original and summed decomposed pulse wave. Several studies have demonstrated that these kinds of measures predict cardiovascular events. While dynamic factors, e.g., arterial stiffness, depend on fixed structural features of the vascular wall. Arterial stiffness is estimated based on pulse wave decomposition analysis in the radial and tibial arteries. Elucidation of the precise relationship between endothelial function and vascular stiffness awaits still further study.

Identification and characterization of glycosyltransferases involved in the synthesis of the side chains of the cell wall pectic polysaccharide rhamnogalacturonan II

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Neill, Malcolm

Our goal was to gain insight into the genes and proteins involved in the biosynthesis of rhamnogalacturonan II (RG-II), a borate cross-linked and structurally conserved pectic polysaccharide present in the primary cell walls of all vascular plants. The research conducted during the funding period established that (i) Avascular plants have the ability to synthesize UDP-apiose but lack the glycosyltransferase machinery required to synthesize RG-II or other apiose-containing cell wall glycans. (ii) RG-II structure is highly conserved in the Lemnaceae (duckweeds and relatives). However, the structures of other wall pectins and hemicellulose have changed substantial during the diversification of the Lemnaceae.more » This supports the notion that a precise structure of RG-II must be maintained to allow borate cross-linking to occur in a controlled manner. (iii) Enzymes involved in the conversion of UDP-GlcA to UDP-Api, UDP-Xyl, and UDP-Ara may have an important role in controlling the composition of duckweed cell walls. (iv) RG-II exists as the borate ester cross-linked dimer in the cell walls of soybean root hairs and roots. Thus, RG-II is present in the walls of plants cells that grow by tip or by expansive growth. (v) A reduction in RG-II cross-linking in the maize tls1 mutant, which lacks a borate channel protein, suggests that the growth defects observed in the mutant are, at least in part, due to defects in the cell wall.« less

Artery buckling analysis using a two-layered wall model with collagen dispersion.

PubMed

Mottahedi, Mohammad; Han, Hai-Chao

2016-07-01

Artery buckling has been proposed as a possible cause for artery tortuosity associated with various vascular diseases. Since microstructure of arterial wall changes with aging and diseases, it is essential to establish the relationship between microscopic wall structure and artery buckling behavior. The objective of this study was to developed arterial buckling equations to incorporate the two-layered wall structure with dispersed collagen fiber distribution. Seven porcine carotid arteries were tested for buckling to determine their critical buckling pressures at different axial stretch ratios. The mechanical properties of these intact arteries and their intima-media layer were determined via pressurized inflation test. Collagen alignment was measured from histological sections and modeled by a modified von-Mises distribution. Buckling equations were developed accordingly using microstructure-motivated strain energy function. Our results demonstrated that collagen fibers disperse around two mean orientations symmetrically to the circumferential direction (39.02°±3.04°) in the adventitia layer; while aligning closely in the circumferential direction (2.06°±3.88°) in the media layer. The microstructure based two-layered model with collagen fiber dispersion described the buckling behavior of arteries well with the model predicted critical pressures match well with the experimental measurement. Parametric studies showed that with increasing fiber dispersion parameter, the predicted critical buckling pressure increases. These results validate the microstructure-based model equations for artery buckling and set a base for further studies to predict the stability of arteries due to microstructural changes associated with vascular diseases and aging. Copyright © 2016 Elsevier Ltd. All rights reserved.

The angiotensin receptor blocker losartan reduces coronary arteriole remodeling in type 2 diabetic mice.

PubMed

Husarek, Kathryn E; Katz, Paige S; Trask, Aaron J; Galantowicz, Maarten L; Cismowski, Mary J; Lucchesi, Pamela A

2016-01-01

Cardiovascular complications are a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM) and are associated with alterations of blood vessel structure and function. Although endothelial dysfunction and aortic stiffness have been documented, little is known about the effects of T2DM on coronary microvascular structural remodeling. The renin-angiotensin-aldosterone system plays an important role in large artery stiffness and mesenteric vessel remodeling in hypertension and T2DM. The goal of this study was to determine whether the blockade of AT1R signaling dictates vascular smooth muscle growth that partially underlies coronary arteriole remodeling in T2DM. Control and db/db mice were given AT1R blocker losartan via drinking water for 4 weeks. Using pressure myography, we found that coronary arterioles from 16-week db/db mice undergo inward hypertrophic remodeling due to increased wall thickness and wall-to-lumen ratio with a decreased lumen diameter. This remodeling was accompanied by decreased elastic modulus (decreased stiffness). Losartan treatment decreased wall thickness, wall-to-lumen ratio, and coronary arteriole cell number in db/db mice. Losartan treatment did not affect incremental elastic modulus. However, losartan improved coronary flow reserve. Our data suggest that Ang II-AT1R signaling mediates, at least in part, coronary arteriole inward hypertrophic remodeling in T2DM without affecting vascular mechanics, further suggesting that targeting the coronary microvasculature in T2DM may help reduce cardiac ischemic events. Copyright © 2015 Elsevier Inc. All rights reserved.

Deleterious effects of tributyltin on porcine vascular stem cells physiology.

PubMed

Bernardini, Chiara; Zannoni, Augusta; Bertocchi, Martina; Bianchi, Francesca; Salaroli, Roberta; Botelho, Giuliana; Bacci, Maria Laura; Ventrella, Vittoria; Forni, Monica

2016-01-01

The vascular functional and structural integrity is essential for the maintenance of the whole organism and it has been demonstrated that different types of vascular progenitor cells resident in the vessel wall play an important role in this process. The purpose of the present research was to observe the effect of tributyltin (TBT), a risk factor for vascular disorders, on porcine Aortic Vascular Precursor Cells (pAVPCs) in term of cytotoxicity, gene expression profile, functionality and differentiation potential. We have demonstrated that pAVPCs morphology deeply changed following TBT treatment. After 48h a cytotoxic effect has been detected and Annexin binding assay demonstrated that TBT induced apoptosis. The transcriptional profile of characteristic pericyte markers has been altered: TBT 10nM substantially induced alpha-SMA, while, TBT 500nM determined a significant reduction of all pericyte markers. IL-6 protein detected in the medium of pAVPCs treated with TBT at both doses studied and with a dose response. TBT has interfered with normal pAVPC functionality preventing their ability to support a capillary-like network. In addition TBT has determined an increase of pAVPC adipogenic differentiation. In conclusion in the present paper we have demonstrated that TBT alters the vascular stem cells in terms of structure, functionality and differentiating capability, therefore effects of TBT in blood should be deeply explored to understand the potential vascular risk associated with the alteration of vascular stem cell physiology. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultrastructure and Composition of the Nannochloropsis gaditana Cell Wall

PubMed Central

Scholz, Matthew J.; Weiss, Taylor L.; Jinkerson, Robert E.; Jing, Jia; Roth, Robyn; Goodenough, Ursula; Posewitz, Matthew C.

2014-01-01

Marine algae of the genus Nannochloropsis are promising producers of biofuel precursors and nutraceuticals and are also harvested commercially for aquaculture feed. We have used quick-freeze, deep-etch electron microscopy, Fourier transform infrared spectroscopy, and carbohydrate analyses to characterize the architecture of the Nannochloropsis gaditana (strain CCMP 526) cell wall, whose recalcitrance presents a significant barrier to biocommodity extraction. The data indicate a bilayer structure consisting of a cellulosic inner wall (∼75% of the mass balance) protected by an outer hydrophobic algaenan layer. Cellulase treatment of walls purified after cell lysis generates highly enriched algaenan preparations without using the harsh chemical treatments typically used in algaenan isolation and characterization. Nannochloropsis algaenan was determined to comprise long, straight-chain, saturated aliphatics with ether cross-links, which closely resembles the cutan of vascular plants. Chemical identification of >85% of the isolated cell wall mass is detailed, and genome analysis is used to identify candidate biosynthetic enzymes. PMID:25239976

Easy Come, Easy Go: Capillary Forces Enable Rapid Refilling of Embolized Primary Xylem Vessels.

PubMed

Rolland, Vivien; Bergstrom, Dana M; Lenné, Thomas; Bryant, Gary; Chen, Hua; Wolfe, Joe; Holbrook, N Michele; Stanton, Daniel E; Ball, Marilyn C

2015-08-01

Protoxylem plays an important role in the hydraulic function of vascular systems of both herbaceous and woody plants, but relatively little is known about the processes underlying the maintenance of protoxylem function in long-lived tissues. In this study, embolism repair was investigated in relation to xylem structure in two cushion plant species, Azorella macquariensis and Colobanthus muscoides, in which vascular water transport depends on protoxylem. Their protoxylem vessels consisted of a primary wall with helical thickenings that effectively formed a pit channel, with the primary wall being the pit channel membrane. Stem protoxylem was organized such that the pit channel membranes connected vessels with paratracheal parenchyma or other protoxylem vessels and were not exposed directly to air spaces. Embolism was experimentally induced in excised vascular tissue and detached shoots by exposing them briefly to air. When water was resupplied, embolized vessels refilled within tens of seconds (excised tissue) to a few minutes (detached shoots) with water sourced from either adjacent parenchyma or water-filled vessels. Refilling occurred in two phases: (1) water refilled xylem pit channels, simplifying bubble shape to a rod with two menisci; and (2) the bubble contracted as the resorption front advanced, dissolving air along the way. Physical properties of the protoxylem vessels (namely pit channel membrane porosity, hydrophilic walls, vessel dimensions, and helical thickenings) promoted rapid refilling of embolized conduits independent of root pressure. These results have implications for the maintenance of vascular function in both herbaceous and woody species, because protoxylem plays a major role in the hydraulic systems of leaves, elongating stems, and roots. © 2015 American Society of Plant Biologists. All Rights Reserved.

In situ microscopy reveals reversible cell wall swelling in kelp sieve tubes: one mechanism for turgor generation and flow control?

PubMed

Knoblauch, Jan; Tepler Drobnitch, Sarah; Peters, Winfried S; Knoblauch, Michael

2016-08-01

Kelps, brown algae (Phaeophyceae) of the order Laminariales, possess sieve tubes for the symplasmic long-distance transport of photoassimilates that are evolutionarily unrelated but structurally similar to the tubes in the phloem of vascular plants. We visualized sieve tube structure and wound responses in fully functional, intact Bull Kelp (Nereocystis luetkeana [K. Mertens] Postels & Ruprecht 1840). In injured tubes, apparent slime plugs formed but were unlikely to cause sieve tube occlusion as they assembled at the downstream side of sieve plates. Cell walls expanded massively in the radial direction, reducing the volume of the wounded sieve elements by up to 90%. Ultrastructural examination showed that a layer of the immediate cell wall characterized by circumferential cellulose fibrils was responsible for swelling and suggested that alginates, abundant gelatinous polymers of the cell wall matrix, were involved. Wall swelling was rapid, reversible and depended on intracellular pressure, as demonstrated by pressure-injection of silicon oil. Our results revive the concept of turgor generation and buffering by swelling cell walls, which had fallen into oblivion over the last century. Because sieve tube transport is pressure-driven and controlled physically by tube diameter, a regulatory role of wall swelling in photoassimilate distribution is implied in kelps. © 2016 John Wiley & Sons Ltd.

The effects of particle size, shape, density and flow characteristics on particle margination to vascular walls in cardiovascular diseases.

PubMed

Ta, Hang T; Truong, Nghia P; Whittaker, Andrew K; Davis, Thomas P; Peter, Karlheinz

2018-01-01

Vascular-targeted drug delivery is a promising approach for the treatment of atherosclerosis, due to the vast involvement of endothelium in the initiation and growth of plaque, a characteristic of atherosclerosis. One of the major challenges in carrier design for targeting cardiovascular diseases (CVD) is that carriers must be able to navigate the circulation system and efficiently marginate to the endothelium in order to interact with the target receptors. Areas covered: This review draws on studies that have focused on the role of particle size, shape, and density (along with flow hemodynamics and hemorheology) on the localization of the particles to activated endothelial cell surfaces and vascular walls under different flow conditions, especially those relevant to atherosclerosis. Expert opinion: Generally, the size, shape, and density of a particle affect its adhesion to vascular walls synergistically, and these three factors should be considered simultaneously when designing an optimal carrier for targeting CVD. Available preliminary data should encourage more studies to be conducted to investigate the use of nano-constructs, characterized by a sub-micrometer size, a non-spherical shape, and a high material density to maximize vascular wall margination and minimize capillary entrapment, as carriers for targeting CVD.

Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yuting, E-mail: yutingl188@gmail.com; Paganetti, Harald; Schuemann, Jan

2015-10-15

Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photonmore » beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor.« less

Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons.

PubMed

Lin, Yuting; Paganetti, Harald; McMahon, Stephen J; Schuemann, Jan

2015-10-01

The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photon beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor.

Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons

PubMed Central

Lin, Yuting; Paganetti, Harald; McMahon, Stephen J.; Schuemann, Jan

2015-01-01

Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photon beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor. PMID:26429263

Molecular mechanisms of maternal vascular dysfunction in preeclampsia.

PubMed

Goulopoulou, Styliani; Davidge, Sandra T

2015-02-01

In preeclampsia, as a heterogeneous syndrome, multiple pathways have been proposed for both the causal as well as the perpetuating factors leading to maternal vascular dysfunction. Postulated mechanisms include imbalance in the bioavailability and activity of endothelium-derived contracting and relaxing factors and oxidative stress. Studies have shown that placenta-derived factors [antiangiogenic factors, microparticles (MPs), cell-free nucleic acids] are released into the maternal circulation and act on the vascular wall to modify the secretory capacity of endothelial cells and alter the responsiveness of vascular smooth muscle cells to constricting and relaxing stimuli. These molecules signal their deleterious effects on the maternal vascular wall via pathways that provide the molecular basis for novel and effective therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Noninvasive assessment of vascular structure and function in conscious rats based on in vivo imaging of the albino iris

PubMed Central

Rarick, Kevin R.; Leick, Katie M.; Burkle, Jason W.; Rotella, Diane L.; Anderson, Michael G.

2011-01-01

Experimental techniques allowing longitudinal studies of vascular disease progression or treatment effects are not readily available for most animal models. Thus, most existing studies are destined to either study individual time points or use large cohorts of animals. Here we describe a noninvasive technique for studying vascular disease that is based on in vivo imaging of the long posterior ciliary artery (LPCA) in the iris of albino rats. Using a slit-lamp biomicroscope, images of the LPCA were taken weekly in conscious normotensive Wistar Kyoto rats (WKY, n = 10) and spontaneously hypertensive rats (SHR, n = 10) for 10 wk. Using imaging software, we found that lumen diameter was significantly smaller and the wall-to-lumen (W/L) ratio larger in SHR than in WKY. Wall thickness was not different. Blood pressure correlated with the W/L ratio. Histology of the abdominal aorta also revealed a smaller lumen diameter and greater W/L ratio in SHR compared with WKY. Corneal application of the muscarinic receptor agonist pilocarpine elicited a dose-dependent vasodilation of the LPCA that could be antagonized by inhibition of nitric oxide synthase, suggesting that the pilocarpine response is mainly mediated by endothelium-derived nitric oxide. Consistent with endothelial dysfunction in SHR, pilocarpine-induced vasodilation was greater in WKY rats than in SHR. These findings indicate that in vivo imaging of the LPCA allows assessment of several structural and functional vascular parameters in conscious rats and that the LPCA responds to disease insults and pharmacologic treatments in a fashion that will make it a useful model for further studies. PMID:21389331

Vascular anatomy of the stomach related to resection procedures strategy.

PubMed

Prudius, V; Procházka, V; Pavlovský, Z; Prudius, D; Kala, Z

2017-04-01

This study is focused on the vascular anatomy of the stomach in relation to the gastric pull-up construction. The vascular anatomy was studied on forty-one human specimens. We find out the differences in blood supplement between anterior and posterior wall. It was maked an review of the main trunk arteries of the stomach. To display the vessels of the stomach we used diaphanoscopy, digital shooting in special mode and micro preparation of the vessels. We find out that left gastric artery gives more branches to the posterior wall and right gastroepiploic artery (RGEA) gives more branches to the anterior wall. But brunches of RGEA are longer on the posterior wall than on the anterior. Also we are offering the new classification of the RGEA related to gastric pull-up construction. This classification based not only on the anatomical shapes of RGEA but on the properties of the flow dynamics through the artery.

Quantitative 3D reconstruction of airway and pulmonary vascular trees using HRCT

NASA Astrophysics Data System (ADS)

Wood, Susan A.; Hoford, John D.; Hoffman, Eric A.; Zerhouni, Elias A.; Mitzner, Wayne A.

1993-07-01

Accurate quantitative measurements of airway and vascular dimensions are essential to evaluate function in the normal and diseased lung. In this report, a novel method is described for three-dimensional extraction and analysis of pulmonary tree structures using data from High Resolution Computed Tomography (HRCT). Serially scanned two-dimensional slices of the lower left lobe of isolated dog lungs were stacked to create a volume of data. Airway and vascular trees were three-dimensionally extracted using a three dimensional seeded region growing algorithm based on difference in CT number between wall and lumen. To obtain quantitative data, we reduced each tree to its central axis. From the central axis, branch length is measured as the distance between two successive branch points, branch angle is measured as the angle produced by two daughter branches, and cross sectional area is measured from a plane perpendicular to the central axis point. Data derived from these methods can be used to localize and quantify structural differences both during changing physiologic conditions and in pathologic lungs.

The coupled bio-chemo-electro-mechanical behavior of glucose exposed arterial elastin

NASA Astrophysics Data System (ADS)

Zhang, Yanhang; Li, Jiangyu; Boutis, Gregory S.

2017-04-01

Elastin, the principle protein component of the elastic fiber, is a critical extracellular matrix (ECM) component of the arterial wall providing structural resilience and biological signaling essential in vascular morphogenesis and maintenance of mechanical homeostasis. Pathogenesis of many cardiovascular diseases have been associated with alterations of elastin. As a long-lived ECM protein that is deposited and organized before adulthood, elastic fibers can suffer from cumulative effects of biochemical exposure encountered during aging and/or disease, which greatly compromise their mechanical function. This review article covers findings from recent studies of the mechanical and structural contribution of elastin to vascular function, and the effects of biochemical degradation. Results from diverse experimental methods including tissue-level mechanical characterization, fiber-level nonlinear optical imaging, piezoelectric force microscopy, and nuclear magnetic resonance are reviewed. The intriguing coupled bio-chemo-electro-mechanical behavior of elastin calls for a multi-scale and multi-physical understanding of ECM mechanics and mechanobiology in vascular remodeling.

Impact of magnesium:calcium ratio on calcification of the aortic wall.

PubMed

Villa-Bellosta, Ricardo

2017-01-01

An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.

Fabrication of cell penetration enhanced poly (l-lactic acid-co-ɛ-caprolactone)/silk vascular scaffolds utilizing air-impedance electrospinning.

PubMed

Yin, Anlin; Li, Jiukai; Bowlin, Gary L; Li, Dawei; Rodriguez, Isaac A; Wang, Jing; Wu, Tong; Ei-Hamshary, Hany A; Al-Deyab, Salem S; Mo, Xiumei

2014-08-01

In the vascular prosthetic field, the prevailing thought is that for clinical, long-term success, especially bioresorbable grafts, cellular migration and penetration into the prosthetic structure is required to promote neointima formation and vascular wall development. In this study, we fabricated poly (l-lactic acid-co-ɛ-caprolactone) P(LLA-CL)/silk fibroin (SF) vascular scaffolds through electrospinning using both perforated mandrel subjected to various intraluminal air pressures (0-300kPa), and solid mandrel. The scaffolds were evaluated the cellular infiltration in vitro and mechanical properties. Vascular scaffolds were seeded with smooth muscle cells (SMCs) to evaluate cellular infiltration at 1, 7, and 14 days. The results revealed that air-impedance scaffolds allowed significantly more cell infiltration as compared to the scaffolds fabricated with solid mandrel. Meanwhile, results showed that both mandrel model and applied air pressure determined the interfiber distance and the alignment of fibers in the enhanced porosity regions of the structure which influenced cell infiltration. Uniaxial tensile testing indicated that the air-impedance scaffolds have sufficient ultimate strength, suture retention strength, and burst pressure as well as compliance approximating a native artery. In conclusion, the air-impedance scaffolds improved cellular infiltration without compromising overall biomechanical properties. These results support the scaffold's potential for vascular grafting and in situ regeneration. Copyright © 2014 Elsevier B.V. All rights reserved.

Early treatment with losartan effectively ameliorates hypertension and improves vascular remodeling and function in a prehypertensive rat model.

PubMed

He, De-Hua; Lin, Jin-Xiu; Zhang, Liang-Min; Xu, Chang-Sheng; Xie, Qiang

2017-03-15

Pharmacological treatment of prehypertension may ameliorate hypertension and improve vascular structure and function. This study investigated 1) whether early treatment with either losartan or amlodipine at the onset of prehypertension can prevent hypertension and 2) whether losartan and amlodipine equally improve vascular remodeling and function in a rat model of hypertension. Stroke-prone spontaneously hypertensive (SHRSP) rats were administered losartan, amlodipine or saline for 6 or 16weeks at the onset of prehypertension. Wistar-Kyoto rats were used as a control. All groups were observed for 40weeks. Systolic blood pressure was measured using the tail-cuff method. Vascular structure and function were determined by microscopy and vascular ring contractility assays, respectively. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassays. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression was measured by western blot. Losartan effectively reduced progression from prehypertension to hypertension as well as vascular remodeling and improved vascular contractility in SHRSP rats. Long-term losartan (16weeks) had greater benefits than short-term (6weeks) treatment. Losartan increased Ang II and decreased Aldo levels in the serum and vessel walls of resistance vessels in a time-dependent manner. Losartan significantly decreased AT1R and increased AT2R vascular expression. Amlodipine had no effect on vascular AT1R and AT2R expression. Losartan administered at the onset of prehypertension is more effective than amlodipine in ameliorating hypertension and improving vascular remodeling and function, which is likely mediated by the renin-angiotensin-aldosterone system. Copyright © 2017 Elsevier Inc. All rights reserved.

Cellular Model of Atherogenesis Based on Pluripotent Vascular Wall Pericytes.

PubMed

Ivanova, Ekaterina A; Orekhov, Alexander N

2016-01-01

Pericytes are pluripotent cells that can be found in the vascular wall of both microvessels and large arteries and veins. They have distinct morphology with long branching processes and form numerous contacts with each other and with endothelial cells, organizing the vascular wall cells into a three-dimensional network. Accumulating evidence demonstrates that pericytes may play a key role in the pathogenesis of vascular disorders, including atherosclerosis. Macrovascular pericytes are able to accumulate lipids and contribute to growth and vascularization of the atherosclerotic plaque. Moreover, they participate in the local inflammatory process and thrombosis, which can lead to fatal consequences. At the same time, pericytes can represent a useful model for studying the atherosclerotic process and for the development of novel therapeutic approaches. In particular, they are suitable for testing various substances' potential for decreasing lipid accumulation induced by the incubation of cells with atherogenic low-density lipoprotein. In this review we will discuss the application of cellular models for studying atherosclerosis and provide several examples of successful application of these models to drug research.

Vascular lysyl oxidase over-expression alters extracellular matrix structure and induces oxidative stress.

PubMed

Varona, Saray; García-Redondo, Ana B; Martínez-González, Jose; Salaices, Mercedes; Briones, Ana M; Rodríguez, Cristina

Lysyl oxidase (LOX) participates in the assembly of collagen and elastin fibres. The impact of vascular LOX over-expression on extracellular matrix (ECM) structure and its contribution to oxidative stress has been analysed. Studies were conducted on mice over-expressing LOX (Tg), specifically in smooth muscle cells (VSMC). Gene expression was assessed by real-time PCR analysis. Sirius Red staining, H 2 O 2 production and NADPH oxidase activity were analysed in different vascular beds. The size and number of fenestra of the internal elastic lamina were determined by confocal microscopy. LOX activity was up-regulated in VSMC of transgenic mice compared with cells from control animals. At the same time, transgenic cells deposited more organised elastin fibres and their supernatants induced a stronger collagen assembly in in vitro assays. Vascular collagen cross-linking was also higher in Tg mice, which showed a decrease in the size of fenestrae and an enhanced expression of Fibulin-5. Interestingly, higher H 2 O 2 production and NADPH oxidase activity was detected in the vascular wall from transgenic mice. The H 2 O 2 scavenger catalase attenuated the stronger deposition of mature elastin fibres induced by LOX transgenesis. LOX over-expression in VSMC was associated with a change in the structure of collagen and elastin fibres. LOX could constitute a novel source of oxidative stress that might participate in elastin changes and contribute to vascular remodelling. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Structural and mechanical design of tissue interfaces in the giant reed Arundo donax.

PubMed

Rüggeberg, Markus; Burgert, Ingo; Speck, Thomas

2010-03-06

The culms of the giant reed Arundo donax represent slender tube-like structures. Several nodes along the culm, a ring of sclerenchymatous fibres in the periphery of the culm wall and numerous isolated vascular bundles enclosed by fibre rings in the culm wall function as stiffening elements. The bundles are embedded in lignified parenchyma. Micromechanical analysis indicated differences in stiffness between the individual tissues of more than one order of magnitude. In case of abrupt transitions in stiffness at the interfaces, stress discontinuities arise under dynamic loads. This eventually leads to critical shear stresses at cell ends, and culm failure may be initiated at these points. Pronounced mechanical differences between individual tissues can be compromised by gradual transitions at their interfaces. Ultrastructural and spectroscopic investigations with high spatial resolution revealed a gradual transition of cell parameters (cell wall area fraction and cell length). However, cell wall parameters (cellulose microfibril angle and lignin content) showed abrupt transitions or remained almost constant across the interfaces between various tissues. The design principles found at the interfaces between tissues in the culm walls of A. donax are discussed as an adaptation strategy to mechanical loads at different levels of hierarchy.

Structural and mechanical design of tissue interfaces in the giant reed Arundo donax

PubMed Central

Rüggeberg, Markus; Burgert, Ingo; Speck, Thomas

2010-01-01

The culms of the giant reed Arundo donax represent slender tube-like structures. Several nodes along the culm, a ring of sclerenchymatous fibres in the periphery of the culm wall and numerous isolated vascular bundles enclosed by fibre rings in the culm wall function as stiffening elements. The bundles are embedded in lignified parenchyma. Micromechanical analysis indicated differences in stiffness between the individual tissues of more than one order of magnitude. In case of abrupt transitions in stiffness at the interfaces, stress discontinuities arise under dynamic loads. This eventually leads to critical shear stresses at cell ends, and culm failure may be initiated at these points. Pronounced mechanical differences between individual tissues can be compromised by gradual transitions at their interfaces. Ultrastructural and spectroscopic investigations with high spatial resolution revealed a gradual transition of cell parameters (cell wall area fraction and cell length). However, cell wall parameters (cellulose microfibril angle and lignin content) showed abrupt transitions or remained almost constant across the interfaces between various tissues. The design principles found at the interfaces between tissues in the culm walls of A. donax are discussed as an adaptation strategy to mechanical loads at different levels of hierarchy. PMID:19726440

Vitamins E and C - effects on matrix components in the vascular system

USDA-ARS?s Scientific Manuscript database

The connective tissue in the vascular system, consisting mainly of vascular smooth muscle cells (VSMC) and the interstitial extracellular matrix (ECM), plays important roles in the maintenance of an intact vascular wall as well as in the repair of atherosclerotic lesions during disease development. ...

Characterization of xylan in the early stages of secondary cell wall formation in tobacco bright yellow-2 cells.

PubMed

Ishii, Tadashi; Matsuoka, Keita; Ono, Hiroshi; Ohnishi-Kameyama, Mayumi; Yaoi, Katsuro; Nakano, Yoshimi; Ohtani, Misato; Demura, Taku; Iwai, Hiroaki; Satoh, Shinobu

2017-11-15

The major polysaccharides present in the primary and secondary walls surrounding plant cells have been well characterized. However, our knowledge of the early stages of secondary wall formation is limited. To address this, cell walls were isolated from differentiating xylem vessel elements of tobacco bright yellow-2 (BY-2) cells induced by VASCULAR-RELATED NAC-DOMAIN7 (VND7). The walls of induced VND7-VP16-GR BY-2 cells consisted of cellulose, pectic polysaccharides, hemicelluloses, and lignin, and contained more xylan and cellulose compared with non-transformed BY-2 and uninduced VND7-VP16-GR BY-2 cells. A reducing end sequence of xylan containing rhamnose and galaturonic acid- residues is present in the walls of induced, uninduced, and non-transformed BY-2 cells. Glucuronic acid residues in xylan from walls of induced cells are O-methylated, while those of xylan in non-transformed BY-2 and uninduced cells are not. Our results show that xylan changes in chemical structure and amounts during the early stages of xylem differentiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

New therapeutic options for the metabolic syndrome: what's next?

PubMed

Flordellis, Christodoulos S; Ilias, Ioannis; Papavassiliou, Athanasios G

2005-08-01

The metabolic syndrome (MSX), characterized by obesity, insulin resistance, dyslipidemia and hypertension, increases the risk of cardiovascular morbidity and mortality. It has recently been hypothesized that MSX and type 2 diabetes are caused by triglyceride and long-chain fatty acid accumulation in liver, muscle, pancreatic islets and selected brain areas. This lipocentric approach is integrated with analysis of inflammation associated with end-organ damage, including the vascular wall. Genes and proteins contributing to insulin resistance, beta cell dysfunction and vascular wall damage have been identified. Transcription factors and coactivators, including peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 are crucial in mediating insulin resistance and accelerating vascular wall inflammation, and represent promising therapeutic targets. New pharmacological strategies include dual PPARalpha/gamma agonists, drugs with pleiotropic effects or combination therapies.

Plasma Protein Corona Modulates the Vascular Wall Interaction of Drug Carriers in a Material and Donor Specific Manner

PubMed Central

Sobczynski, Daniel J.; Charoenphol, Phapanin; Heslinga, Michael J.; Onyskiw, Peter J.; Namdee, Katawut; Thompson, Alex J.; Eniola-Adefeso, Omolola

2014-01-01

The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid) (PLGA) spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer) is seen with ∼60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases. PMID:25229244

Impact of magnesium:calcium ratio on calcification of the aortic wall

PubMed Central

2017-01-01

Objective An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Approach and results Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Conclusion Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio. PMID:28570619

Structural analysis of two different stent configurations.

PubMed

Simão, M; Ferreira, J M; Mora-Rodriguez, J; Ramos, H M

2017-06-01

Two different stent configurations (i.e. the well known Palmaz-Schatz (PS) and a new stent configuration) are mechanically investigated. A finite element model was used to study the two geometries under combining loads and a computational fluid dynamic model based on fluid structure interaction was developed investigating the plaque and the artery wall reactions in a stented arterial segment. These models determine the stress and displacement fields of the two stents under internal pressure conditions. Results suggested that stent designs cause alterations in vascular anatomy that adversely affect arterial stress distributions within the wall, which have impact in the vessel responses such as the restenosis. The hemodynamic analysis shows the use of new stent geometry suggests better biofluid mechanical response such as the deformation and the progressive amount of plaque growth.

Cell wall polysaccharides from fern leaves: evidence for a mannan-rich Type III cell wall in Adiantum raddianum.

PubMed

Silva, Giovanna B; Ionashiro, Mari; Carrara, Thalita B; Crivellari, Augusto C; Tiné, Marco A S; Prado, Jefferson; Carpita, Nicholas C; Buckeridge, Marcos S

2011-12-01

Primary cell walls from plants are composites of cellulose tethered by cross-linking glycans and embedded in a matrix of pectins. Cell wall composition varies between plant species, reflecting in some instances the evolutionary distance between them. In this work the monosaccharide compositions of isolated primary cell walls of nine fern species and one lycophyte were characterized and compared with those from Equisetum and an angiosperm dicot. The relatively high abundance of mannose in these plants suggests that mannans may constitute the major cross-linking glycan in the primary walls of pteridophytes and lycophytes. Pectin-related polysaccharides contained mostly rhamnose and uronic acids, indicating the presence of rhamnogalacturonan I highly substituted with galactose and arabinose. Structural and fine-structural analyses of the hemicellulose fraction of leaves of Adiantum raddianum confirmed this hypothesis. Linkage analysis showed that the mannan contains mostly 4-Man with very little 4,6-Man, indicating a low percentage of branching with galactose. Treatment of the mannan-rich fractions with endo-β-mannanase produced characteristic mannan oligosaccharides. Minor amounts of xyloglucan and xylans were also detected. These data and those of others suggest that all vascular plants contain xyloglucans, arabinoxylans, and (gluco)mannans, but in different proportions that define cell wall types. Whereas xyloglucan and pectin-rich walls define Type I walls of dicots and many monocots, arabinoxylans and lower proportion of pectin define the Type II walls of commelinoid monocots. The mannan-rich primary walls with low pectins of many ferns and a lycopod indicate a fundamentally different wall type among land plants, the Type III wall. Copyright © 2011 Elsevier Ltd. All rights reserved.

Building a functional artery: issues from the perspective of mechanics.

PubMed

Gleason, Rudolph L; Hu, Jin-Jia; Humphrey, Jay D

2004-09-01

Despite the many successes of arterial tissue engineering, clinically viable implants may be a decade or more away. Fortunately, there is much more that we can learn from native vessels with regard to designing for optimal structure, function, and properties. Herein, we examine recent observations in vascular biology from the perspective of nonlinear mechanics. Moreover, we use a constrained mixture model to study potential contributions of individual wall constituents. In both cases, the unique biological and mechanical roles of elastin come to the forefront, especially its role in generating and modulating residual stress within the wall, which appears to be key to multiple growth and remodeling responses.

The circumventricular organs: an atlas of comparative anatomy and vascularization.

PubMed

Duvernoy, Henri M; Risold, Pierre-Yves

2007-11-01

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.

Celiprolol

PubMed Central

Cheng-Lai, Angela; Frishman, William H.

2017-01-01

Celiprolol is a β-blocker with a unique pharmacologic profile: it is a β1-andrenoceptor antagonist with partial β2 agonist activity. Given this combination of effects, celiprolol may be better described as a selective adrenoreceptor modulator. It has antihypertensive and antianginal properties and is indicated for those uses in various countries around the world. In the United States, however, the proposed indication for this drug will be for the treatment of vascular type Ehlers–Danlos syndrome, a rare connective tissue disorder characterized by fragile arterial structure and an increased risk of life-threatening vascular complications. By reducing heart rate and pulsatile pressure, celiprolol may reduce the mechanical stress on collagen fibers within the arterial wall and be of benefit in patients with vascular type Ehlers–Danlos syndrome. The largest investigation of celiprolol in vascular Ehlers–Danlos syndrome was prematurely terminated due to significant benefit with celiprolol in reducing arterial events in patients with this condition. Celiprolol, therefore, represents a β-blocker that is unique from others in its class in both its pharmacology and clinical applications. PMID:28742547

The antivascular action of physiotherapy ultrasound on murine tumors.

PubMed

Wood, Andrew K W; Ansaloni, Sara; Ziemer, Lisa S; Lee, William M-F; Feldman, Michael D; Sehgal, Chandra M

2005-10-01

This study was aimed at determining if physiotherapy ultrasound (US) affected the fragile and leaky angiogenic blood vessels in a tumor. In 22 C3HV/HeN mice, a subcutaneous melanoma (K1735(22)) was insonated (1, 2 or 3 min) with continuous 1-MHz low-intensity (spatial-average temporal-average = 2.28 W cm(-2)), physiotherapy US. Contrast-enhanced (0.1 mL Optison) power Doppler US observations were made and histogram analyses of the images were performed. Before insonation, all but 7% of the tumor was perfused. The avascular area in tumors receiving 3-min treatment increased to 82% (p < 0.001). A linear regression analysis showed that each min of insonation led to a 25% reduction in tumor vascularity; the antivascular activity persisted for 24 h. Histology demonstrated disruption of vascular walls and tumor cell death in areas of vascular congestion and thrombosis. Physiotherapy US particularly targeted the vascular structures, and the effects on tumor cells appeared to be secondary to the resultant ischemia.

pyNS: an open-source framework for 0D haemodynamic modelling.

PubMed

Manini, Simone; Antiga, Luca; Botti, Lorenzo; Remuzzi, Andrea

2015-06-01

A number of computational approaches have been proposed for the simulation of haemodynamics and vascular wall dynamics in complex vascular networks. Among them, 0D pulse wave propagation methods allow to efficiently model flow and pressure distributions and wall displacements throughout vascular networks at low computational costs. Although several techniques are documented in literature, the availability of open-source computational tools is still limited. We here present python Network Solver, a modular solver framework for 0D problems released under a BSD license as part of the archToolkit ( http://archtk.github.com ). As an application, we describe patient-specific models of the systemic circulation and detailed upper extremity for use in the prediction of maturation after surgical creation of vascular access for haemodialysis.

Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling

PubMed Central

Makino, Ayako; Firth, Amy L.; Yuan, Jason X.-J.

2017-01-01

The pulmonary circulation is a low resistance and low pressure system. Sustained pulmonary vasoconstriction and excessive vascular remodeling often occur under pathophysiological conditions such as in patients with pulmonary hypertension. Pulmonary vasoconstriction is a consequence of smooth muscle contraction. Many factors released from the endothelium contribute to regulating pulmonary vascular tone, while the extracellular matrix in the adventitia is the major determinant of vascular wall compliance. Pulmonary vascular remodeling is characterized by adventitial and medial hypertrophy due to fibroblast and smooth muscle cell proliferation, neointimal proliferation, intimal, and plexiform lesions that obliterate the lumen, muscularization of precapillary arterioles, and in situ thrombosis. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction, while increased release of mitogenic factors, upregulation (or downregulation) of ion channels and transporters, and abnormalities in intracellular signaling cascades are key to the remodeling of the pulmonary vasculature. Changes in the expression, function, and regulation of ion channels in PASMC and pulmonary arterial endothelial cells play an important role in the regulation of vascular tone and development of vascular remodeling. This article will focus on describing the ion channels and transporters that are involved in the regulation of pulmonary vascular function and structure and illustrating the potential pathogenic role of ion channels and transporters in the development of pulmonary vascular disease. PMID:23733654

Immuno and Affinity Cytochemical Analysis of Cell Wall Composition in the Moss Physcomitrella patens.

PubMed

Berry, Elizabeth A; Tran, Mai L; Dimos, Christos S; Budziszek, Michael J; Scavuzzo-Duggan, Tess R; Roberts, Alison W

2016-01-01

In contrast to homeohydric vascular plants, mosses employ a poikilohydric strategy for surviving in the dry aerial environment. A detailed understanding of the structure, composition, and development of moss cell walls can contribute to our understanding of not only the evolution of overall cell wall complexity, but also the differences that have evolved in response to selection for different survival strategies. The model moss species Physcomitrella patens has a predominantly haploid lifecycle consisting of protonemal filaments that regenerate from protoplasts and enlarge by tip growth, and leafy gametophores composed of cells that enlarge by diffuse growth and differentiate into several different types. Advantages for genetic studies include methods for efficient targeted gene modification and extensive genomic resources. Immuno and affinity cytochemical labeling were used to examine the distribution of polysaccharides and proteins in regenerated protoplasts, protonemal filaments, rhizoids, and sectioned gametophores of P. patens. The cell wall composition of regenerated protoplasts was also characterized by flow cytometry. Crystalline cellulose was abundant in the cell walls of regenerating protoplasts and protonemal cells that developed on media of high osmolarity, whereas homogalactuonan was detected in the walls of protonemal cells that developed on low osmolarity media and not in regenerating protoplasts. Mannan was the major hemicellulose detected in all tissues tested. Arabinogalactan proteins were detected in different cell types by different probes, consistent with structural heterogneity. The results reveal developmental and cell type specific differences in cell wall composition and provide a basis for analyzing cell wall phenotypes in knockout mutants.

Exploring ischemia-induced vascular lesions and potential pharmacological intervention strategies.

PubMed

Aliev, G; Obrenovich, M E; Seyidova, D; de la Torre, J C

2005-01-01

Structural changes in vessels under the influence of ischemia play an important role in the pathogenesis of many diseases, most important of which are stroke and myocardial infarction or myocardial insult. Over the years, information has been gathered, which implicate a role for ischemic vascular changes in the pathogenesis of crush-syndrome, atherosclerosis and other vascular diseases. When blood vessels are damaged they become unresponsive to a stimulus, which normally elicits vasodilatation and can lead to intraluminal thrombosis and ischemic events. The aim of this review is to explore the structural changes seen in vessels affected by ischemia reperfusion injury. With ischemia, the development of observable changes to vascular structure is multifactorial. One key factor is reperfusion ischemic injury. Moreover, the duration of the ischemic event is an important factor when determining both the prognosis and the type of morphological change that is observable in affected vessel walls. In this regard, the deleterious progression of blood flow impairment and its severity depends on the specific organ involved and the type of tissue affected. Further, there are regional differences within affected tissues and the degree of microvascular injury is well correlated with differences in the nature and severity of the ischemic event. Any method aimed at preventing and treating ischemic reperfusion injuries in vessels, based on these investigations, should likewise be able to decrease the early signs of brain, cerebrovascular and heart injury and preserve normal cellular architecture.

A promising biodegradable magnesium alloy suitable for clinical vascular stent application

PubMed Central

Mao, Lin; shen, Li; Chen, Jiahui; Zhang, Xiaobo; Kwak, Minsuk; Wu, Yu; Fan, Rong; Zhang, Lei; Pei, Jia; Yuan, Guangyin; Song, Chengli; Ge, Junbo; Ding, Wenjiang

2017-01-01

We report a Mg alloy Mg-2.2Nd-0.1Zn-0.4Zr (wt.%, denoted as JDBM-2) showing great potential in clinical vascular stent application by integrating the advantages of traditional medical stainless steel and polymer. This alloy exhibits high yield strength and elongation of 276 ± 6 MPa and 34.3 ± 3.4% respectively. The JDBM-2 with a stable degradation surface results in a highly homogeneous degradation mechanism and long-term structural and mechanical durability. In vitro cytotoxicity test of the Mg extract via human vascular endothelial cells (HUVECs) indicates that the corrosion products are well tolerated by the tested cells and potentially negligible toxic effect on arterial vessel walls. This alloy also exhibits compromised foreign body response (FBR) determined by human peripheral blood derived macrophage adhesion, foreign body giant cell (FBGC) formation and inflammatory cytokine and chemokine secretion. Finally, vascular stents manufactured from the JDBM-2 were implanted into rabbits for long-term evaluation. The results confirm excellent tissue compatibility and up to 6-month structural and mechanical integrity of the stent in vivo. Thus, the JDBM-2 stent with up to 6-month structural and mechanical integrity and excellent tissue compatibility represents a major breakthrough in this field and a promising alternative to traditional medical stainless steel and polymer for the clinical application. PMID:28397881

Cavitation Resistance in Seedless Vascular Plants: The Structure and Function of Interconduit Pit Membranes1[W][OPEN

PubMed Central

Brodersen, Craig; Jansen, Steven; Choat, Brendan; Rico, Christopher; Pittermann, Jarmila

2014-01-01

Plant water transport occurs through interconnected xylem conduits that are separated by partially digested regions in the cell wall known as pit membranes. These structures have a dual function. Their porous construction facilitates water movement between conduits while limiting the spread of air that may enter the conduits and render them dysfunctional during a drought. Pit membranes have been well studied in woody plants, but very little is known about their function in more ancient lineages such as seedless vascular plants. Here, we examine the relationships between conduit air seeding, pit hydraulic resistance, and pit anatomy in 10 species of ferns (pteridophytes) and two lycophytes. Air seeding pressures ranged from 0.8 ± 0.15 MPa (mean ± sd) in the hydric fern Athyrium filix-femina to 4.9 ± 0.94 MPa in Psilotum nudum, an epiphytic species. Notably, a positive correlation was found between conduit pit area and vulnerability to air seeding, suggesting that the rare-pit hypothesis explains air seeding in early-diverging lineages much as it does in many angiosperms. Pit area resistance was variable but averaged 54.6 MPa s m−1 across all surveyed pteridophytes. End walls contributed 52% to the overall transport resistance, similar to the 56% in angiosperm vessels and 64% in conifer tracheids. Taken together, our data imply that, irrespective of phylogenetic placement, selection acted on transport efficiency in seedless vascular plants and woody plants in equal measure by compensating for shorter conduits in tracheid-bearing plants with more permeable pit membranes. PMID:24777347

Arterial ageing: from endothelial dysfunction to vascular calcification.

PubMed

Tesauro, M; Mauriello, A; Rovella, V; Annicchiarico-Petruzzelli, M; Cardillo, C; Melino, G; Di Daniele, N

2017-05-01

Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Remodeling of Aorta Extracellular Matrix as a Result of Transient High Oxygen Exposure in Newborn Rats: Implication for Arterial Rigidity and Hypertension Risk

PubMed Central

Castro, Michele M.; Cloutier, Anik; Bertagnolli, Mariane; Sartelet, Hervé; Germain, Nathalie; Comte, Blandine; Schulz, Richard; DeBlois, Denis; Nuyt, Anne Monique

2014-01-01

Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular rarefaction, vascular dysfunction and arterial (aorta) rigidity in adult rats. Whether structural changes are present in the matrix of aorta wall is unknown. Considering that elastin synthesis peaks in late fetal life in humans, and early postnatal life in rodents, we postulated that transient neonatal high-oxygen exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control) and were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to angiotensin II and to the acetylcholine analogue carbachol were not different between groups. Vascular superoxide anion production was similar between groups. There was no difference between groups in aortic cross sectional area, smooth muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta elastin/collagen content ratio was significantly decreased, the expression of elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1 staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced, indicating a shift in the balance towards degradation of the extra-cellular matrix and increased deposition of collagen. There was no significant difference in MMP-2 activity between groups as determined by gelatin zymography. Overall, these findings indicate that transient neonatal high oxygen exposure leads to vascular wall alterations (decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen) which are associated with increased rigidity. Importantly, these changes are present prior to the elevation of blood pressure and vascular dysfunction in this model, and may therefore be contributory. PMID:24743169

A clade in the QUASIMODO2 family evolved with vascular plants and supports a role for cell wall composition in adaptation to environmental changes.

PubMed

Fuentes, Sara; Pires, Nuno; Østergaard, Lars

2010-08-01

The evolution of plant vascular tissue is tightly linked to the evolution of specialised cell walls. Mutations in the QUASIMODO2 (QUA2) gene from Arabidopsis thaliana were previously shown to result in cell adhesion defects due to reduced levels of the cell wall component homogalacturonic acid. In this study, we provide additional information about the role of QUA2 and its closest paralogues, QUASIMODO2 LIKE1 (QUL1) and QUL2. Within the extensive QUA2 family, our phylogenetic analysis shows that these three genes form a clade that evolved with vascular plants. Consistent with a possible role of this clade in vasculature development, QUA2 is highly expressed in the vascular tissue of embryos and inflorescence stems and overexpression of QUA2 resulted in temperature-sensitive xylem collapse. Moreover, in-depth characterisation of qua2 qul1 qul2 triple mutant and 35S::QUA2 overexpression plants revealed contrasting temperature-dependent stem development with dramatic effects on stem width. Taken together, our results suggest that the QUA2-specific clade contributed to the evolution of vasculature and illustrate the important role that modification of cell wall composition plays in the adaptation to changing environmental conditions, including changes in temperature.

Impact of dehydration on the forebrain preoptic recess walls in the mudskipper, Periophthalmus modestus: a possible locus for the center of thirst.

PubMed

Hamasaki, Sawako; Mukuda, Takao; Kaidoh, Toshiyuki; Yoshida, Masayuki; Uematsu, Kazumasa

2016-10-01

The forebrain lamina terminalis has not yet been examined for the role of osmosensing in teleosts, although the thirst center is well known to be present in this vascular permeable forebrain region in mammals. Here, we examined vascular permeability and neuronal responsiveness to dehydration in the lamina terminalis of the mudskipper, a euryhaline goby. Evans blue and N-hydroxysulfosuccinimide-biotin both bind to blood proteins, and are impermeable to the blood-brain barrier. Intraperitoneal injection of these probes stained the walls of the preoptic recess (PR) of the third ventricle, indicating increased vascular permeability in this region. When mudskippers kept in isotonic brackish water (ca. 11 psu) were challenged to seawater (ca. 34 psu) for 3 h, body water content showed a 1 % decrease, compared with mudskippers without hypertonic challenge. Simultaneously, the number of immunohistochemically identified cFos-expressing neurons in the anterior parvocellular preoptic nucleus (PPa) of the PR walls increased in a site-specific manner by approximately 1.6-fold compared with controls. Thus, these findings indicate that PPa neurons are activated, following dehydration in mudskippers. Taken together, the vascularly permeable PR walls may be involved in osmosensing, as in the mammalian thirst center.

Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

PubMed Central

Green, Daniel J.; Hopman, Maria T. E.; Padilla, Jaume; Laughlin, M. Harold; Thijssen, Dick H. J.

2017-01-01

On the 400th anniversary of Harvey's Lumleian lectures, this review focuses on “hemodynamic” forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone via paracrine transduction provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the interrelationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions, and the implications for human health. Exercise modifies blood flow, luminal shear stress, arterial pressure, and tangential wall stress, all of which can transduce changes in arterial function, diameter, and wall thickness. There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute to the well-established decrease in cardiovascular risk attributed to physical activity. PMID:28151424

Intracranial Vascular Disease Evaluation With Combined Vessel Wall Imaging And Patient Specific Hemodynamics

NASA Astrophysics Data System (ADS)

Samson, Kurt; Mossa-Basha, Mahmud; Yuan, Chun; Canton, Maria De Gador; Aliseda, Alberto

2017-11-01

Intracranial vascular pathologies are evaluated with angiography, conventional digital subtraction angiography or non-invasive (MRI, CT). Current techniques present limitations on the resolution with which the vessel wall characteristics can be measured, presenting a major challenge to differential diagnostic of cerebral vasculopathies. A new combined approach is presented that incorporates patient-specific image-based CFD models with intracranial vessel-wall MRI (VWMRI). Comparisons of the VWMRI measurements, evaluated for the presence of wall enhancement and thin-walled regions, against CFD metrics such as wall shear stress (WSS), and oscillatory shear index (OSI) are used to understand how the new imaging technique developed can predict the influence of hemodynamics on the deterioration of the aneurysmal wall, leading to rupture. Additionally, histology of each resected aneurysm, evaluated for inflammatory infiltration and wall thickness features, is used to validate the analysis from VWMRI and CFD. This data presents a solid foundation on which to build a new framework for combined VWMRI-CFD to predict unstable wall changes in unruptured intracranial aneurysms, and support clinical monitoring and intervention decisions.

Newly developed surface coil for endoluminal MRI, depiction of pig gastric wall layers and vascular architecture in ex vivo study.

PubMed

Morita, Yoshinori; Kutsumi, Hiromu; Yoshinaka, Hayato; Matsuoka, Yuichiro; Kuroda, Kagayaki; Gotanda, Masakazu; Sekino, Naomi; Kumamoto, Etsuko; Yoshida, Masaru; Inokuchi, Hideto; Azuma, Takeshi

2009-01-01

The purpose of this study was to visualize the gastric wall layers and to depict the vascular architecture in vitro by using resected porcine stomachs studied with high-spatial resolution magnetic resonance (MR) imaging. Normal dissected porcine stomach samples (n = 4) were examined with a 3 Tesla MR system using a newly developed surface coil. MR images were obtained by the surface coil as receiver and a head coil as transmitter. High-spatial-resolution spin-echo MR images were obtained with a field of view of 8 x 8 cm, a matrix of 256 x 128 and slice thicknesses of 3 and 5 mm. T1 and T2-weighted MR images clearly depicted the normal porcine gastric walls as consisting of four distinct layers. In addition, vascular architectures in proper muscle layers were also visualized, which were confirmed by histological examinations to correspond to blood vessels. High-spatial-resolution MR imaging using a surface coil placed closely to the gastric wall enabled the differentiation of porcine gastric wall layers and the depiction of the blood vessels in proper muscle layer in this experimental study.

A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics.

PubMed

Coccarelli, Alberto; Edwards, David Hughes; Aggarwal, Ankush; Nithiarasu, Perumal; Parthimos, Dimitris

2018-02-01

Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α 1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase; and ryanodine, a diterpenoid that modulates Ca 2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca 2+ dynamics. Cytosolic Ca 2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental observations qualitatively, as well as quantitatively within a range of physiological parametric values. The model also illustrated how increased intercellular coupling led to smooth muscle coordination and the genesis of vascular tone. © 2018 The Authors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nose, Y.

Methods were developed for generating an integrated, statistical model of the anatomical structures within the human thorax relevant to radioisotope powered artificial heart implantation. These methods involve measurement and analysis of anatomy in four areas: chest wall, pericardium, vascular connections, and great vessels. A model for the prediction of thorax outline from radiograms was finalized. These models were combined with 100 radiograms to arrive at a size distribution representing the adult male and female populations. (CH)

A video-angiometer for simultaneous and continuous measurement of inner and outer vessel diameters. Technical report.

PubMed

Assmann, R; Henrich, H

1978-09-29

A system is described for continuously measuring vessel diameters. It bases on the evaluation of video signal differences of a video camera which are induced by light intensity differences (grey levels) caused by the vascular wall structures. The system is electronically linear, automatically measuring and in addition eyeball controlled by the human sensor: the inaccuracy does not exceed the 5% level.

The bone morphogenic protein inhibitor, noggin, reduces glycemia and vascular inflammation in db/db mice

PubMed Central

Koga, Mitsuhisa; Engberding, Niels; Dikalova, Anna E.; Chang, Kyung Hwa; Seidel-Rogol, Bonnie; Long, James S.; Lassègue, Bernard; Jo, Hanjoong

2013-01-01

Vascular diseases frequently accompany diabetes mellitus. Based on the current understanding of atherosclerosis as an inflammatory disorder of the vascular wall, it has been speculated that diabetes may accelerate atherosclerosis by inducing a proinflammatory milieu in the vasculature. ANG II and bone morphogenic proteins (BMPs) have been implicated in vascular inflammation. We evaluated the effect of angiotensin receptor blockade by valsartan and BMP inhibition by noggin on markers of vascular inflammation in a mouse model of diabetes. Noggin had no effect on blood pressure but decreased serum glucose levels, whereas valsartan significantly decreased blood pressure, but not serum glucose. Both inhibitors reduced reactive oxygen species production in the aorta. Additionally, noggin and valsartan diminish gene transcription and protein expression of various inflammatory molecules in the vascular wall. These observations indicate that although both inhibitors block superoxide production and have similar effects on inflammatory gene expression, glycemia and blood pressure may represent a secondary target differentially affected by noggin and valsartan. Our data clearly identify the BMP pathway as a potentially potent therapeutic target in diabetic inflammatory vascular disease. PMID:23812391

Mechanosensitivity of Jagged–Notch signaling can induce a switch-type behavior in vascular homeostasis

PubMed Central

Stassen, Oscar M. J. A.; ter Huurne, Fleur M.; Boareto, Marcelo; Sahlgren, Cecilia M.

2018-01-01

Hemodynamic forces and Notch signaling are both known as key regulators of arterial remodeling and homeostasis. However, how these two factors integrate in vascular morphogenesis and homeostasis is unclear. Here, we combined experiments and modeling to evaluate the impact of the integration of mechanics and Notch signaling on vascular homeostasis. Vascular smooth muscle cells (VSMCs) were cyclically stretched on flexible membranes, as quantified via video tracking, demonstrating that the expression of Jagged1, Notch3, and target genes was down-regulated with strain. The data were incorporated in a computational framework of Notch signaling in the vascular wall, where the mechanical load was defined by the vascular geometry and blood pressure. Upon increasing wall thickness, the model predicted a switch-type behavior of the Notch signaling state with a steep transition of synthetic toward contractile VSMCs at a certain transition thickness. These thicknesses varied per investigated arterial location and were in good agreement with human anatomical data, thereby suggesting that the Notch response to hemodynamics plays an important role in the establishment of vascular homeostasis. PMID:29610298

Evolution of the three-dimensional collagen structure in vascular walls during deformation: an in situ mechanical testing under multiphoton microscopy observation.

PubMed

Nierenberger, Mathieu; Fargier, Guillaume; Ahzi, Saïd; Rémond, Yves

2015-08-01

The collagen fibers' three-dimensional architecture has a strong influence on the mechanical behavior of biological tissues. To accurately model this behavior, it is necessary to get some knowledge about the structure of the collagen network. In the present paper, we focus on the in situ characterization of the collagenous structure, which is present in porcine jugular vein walls. An observation of the vessel wall is first proposed in an unloaded configuration. The vein is then put into a mechanical tensile testing device. As the vein is stretched, three-dimensional images of its collagenous structure are acquired using multiphoton microscopy. Orientation analyses are provided for the multiple images recorded during the mechanical test. From these analyses, the reorientation of the two families of collagen fibers existing in the vein wall is quantified. We noticed that the reorientation of the fibers stops as the tissue stiffness starts decreasing, corresponding to the onset of damage. Besides, no relevant evolutions of the out of plane collagen orientations were observed. Due to the applied loading, our analysis also allowed for linking the stress relaxation within the tissue to its internal collagenous structure. Finally, this analysis constitutes the first mechanical test performed under a multiphoton microscope with a continuous three-dimensional observation of the tissue structure all along the test. It allows for a quantitative evaluation of microstructural parameters combined with a measure of the global mechanical behavior. Such data are useful for the development of structural mechanical models for living tissues.

Carbon nanotubes as VEGF carriers to improve the early vascularization of porcine small intestinal submucosa in abdominal wall defect repair

PubMed Central

Liu, Zhengni; Feng, Xueyi; Wang, Huichun; Ma, Jun; Liu, Wei; Cui, Daxiang; Gu, Yan; Tang, Rui

2014-01-01

Insufficient early vascularization in biological meshes, resulting in limited host tissue incorporation, is thought to be the primary cause for the failure of abdominal wall defect repair after implantation. The sustained release of exogenous angiogenic factors from a biocompatible nanomaterial might be a way to overcome this limitation. In the study reported here, multiwalled carbon nanotubes (MWNT) were functionalized by plasma polymerization to deliver vascular endothelial growth factor165 (VEGF165). The novel VEGF165-controlled released system was incorporated into porcine small intestinal submucosa (PSIS) to construct a composite scaffold. Scaffolds incorporating varying amounts of VEGF165-loaded functionalized MWNT were characterized in vitro. At 5 weight percent MWNT, the scaffolds exhibited optimal properties and were implanted in rats to repair abdominal wall defects. PSIS scaffolds incorporating VEGF165-loaded MWNT (VEGF–MWNT–PSIS) contributed to early vascularization from 2–12 weeks postimplantation and obtained more effective collagen deposition and exhibited improved tensile strength at 24 weeks postimplantation compared to PSIS or PSIS scaffolds, incorporating MWNT without VEGF165 loading (MWNT–PSIS). PMID:24648727

Internal Carotid Artery Pseudoaneurysm after Tonsillectomy Treated by Endovascular Approach

PubMed Central

Raffin, C.N.; Montovani, J.C.; Neto, J.M.P.; Campos, C.M.S.; Piske, R.L.

2002-01-01

Summary Surgery on the head and neck region may be complicated by vascular trauma, caused by direct injury on the vascular wall. Lesions of the arteries are more dangerous than the venous one. The traumatic lesion may cause laceration of the artery wall, spasm, dissection, arteriovenous fistula, occlusion or pseudoaneurysm. We present a case of a child with a giant ICA pseudoaneurysm after tonsillectomy, manifested by pulsing mass and respiratory distress, which was treated by endovascular approach, occluding the lesion and the proximal artery with Histoacryl. We reinforce that the endovascular approach is the better way to treat most of the traumatic vascular lesions. PMID:20594516

[Abdominal wall reconstruction with collagen membrane in an animal model of abdominal hernia. A preliminary report].

PubMed

Łukasiewicz, Aleksander; Drewa, Tomasz; Skopińska-Wiśniewska, Joanna; Molski, Stanisław

2008-01-01

Abdominal hernia repair is one of the most common surgical procedures. Current data indicate that the best treatment results are achieved with use of synthetic material to reinforce weakened abdominal wall. Prosthetic materials utilized for hernia repair induce adhesions with underlying viscera. They should be therefore separated from them by a layer of peritoneum otherwise adhesions may cause to serious complications such as bowel-skin fistulas. The aim of our work was to determine if implantation of our collagen membrane into abdominal wall defect induce adhesions in rat model of ventral hernia. The collagen film was obtained by acetic acid extraction of rat tail tendons and than casting the soluble fraction onto polyethylene shits. Abdominal wall defect was created in 10 Wistar male rats. Collagen membranes were implanted into the defect using interrupted polypropylene stitches. After 3 months of observation all animals were sacrificed. No adhesions between path structure and bowel developed. In one often rats (10%) adhesion between fixating stitch and omentum was observed. Complete mesothelium lining and vascular ingrowth were microscopically observed within implanted structure. Promising result requires further confirmation in a larger series of animals.

Hybrid model of arm for analysis of regional blood oxygenation in non-invasive optical diagnostics

NASA Astrophysics Data System (ADS)

Nowocień, Sylwester; Mroczka, Janusz

2017-06-01

The paper presents a new comprehensive approach to modeling and analysis of processes occurring during the blood flow in the arm's small vessels as well as non-invasive measurement method of mixed venous oxygen saturation. During the work, a meta-analysis of available physiological data was performed and based on its result a hybrid model of forearm vascular tree was proposed. The model, in its structure, takes into account a classical nonlinear hydro-electric analogy in conjunction with light-tissue interaction. Several geometries of arm vascular tree obtained from magnetic resonance angiography (MRA) image were analyzed which allowed to proposed the structure of electrical analog network. Proposed model allows to simulate the behavior of forearm blood flow from the vascular tree mechanics point of view, as well as effects of the impact of cuff and vessel wall mechanics on the recorded photoplethysmographic signals. In particular, it allows to analyze the reaction and anatomical effects in small vessels and microcirculation caused by occlusive maneuver in selected techniques, what was of particular interest to authors and motivation to undertake research in this area. Preliminary studies using proposed model showed that inappropriate selection of occlusion maneuver parameters (e.g. occlusion time, cuff pressure etc.), cause dangerous turbulence of blood flow in the venous section of the vascular tree.

Fluid Mechanics, Arterial Disease, and Gene Expression.

PubMed

Tarbell, John M; Shi, Zhong-Dong; Dunn, Jessilyn; Jo, Hanjoong

2014-01-01

This review places modern research developments in vascular mechanobiology in the context of hemodynamic phenomena in the cardiovascular system and the discrete localization of vascular disease. The modern origins of this field are traced, beginning in the 1960s when associations between flow characteristics, particularly blood flow-induced wall shear stress, and the localization of atherosclerotic plaques were uncovered, and continuing to fluid shear stress effects on the vascular lining endothelial) cells (ECs), including their effects on EC morphology, biochemical production, and gene expression. The earliest single-gene studies and genome-wide analyses are considered. The final section moves from the ECs lining the vessel wall to the smooth muscle cells and fibroblasts within the wall that are fluid me chanically activated by interstitial flow that imposes shear stresses on their surfaces comparable with those of flowing blood on EC surfaces. Interstitial flow stimulates biochemical production and gene expression, much like blood flow on ECs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berry, Elizabeth A.; Tran, Mai L.; Dimos, Christos S.

In contrast to homeohydric vascular plants, mosses employ a poikilohydric strategy for surviving in the dry aerial environment. A detailed understanding of the structure, composition, and development of moss cell walls can contribute to our understanding of not only the evolution of overall cell wall complexity, but also the differences that have evolved in response to selection for different survival strategies. The model moss species Physcomitrella patens has a predominantly haploid lifecycle consisting of protonemal filaments that regenerate from protoplasts and enlarge by tip growth, and leafy gametophores composed of cells that enlarge by diffuse growth and differentiate into severalmore » different types. Advantages for genetic studies include methods for efficient targeted gene modification and extensive genomic resources. Immuno and affinity cytochemical labeling were used to examine the distribution of polysaccharides and proteins in regenerated protoplasts, protonemal filaments, rhizoids, and sectioned gametophores of P. patens. The cell wall composition of regenerated protoplasts was also characterized by flow cytometry. Crystalline cellulose was abundant in the cell walls of regenerating protoplasts and protonemal cells that developed on media of high osmolarity, whereas homogalactuonan was detected in the walls of protonemal cells that developed on low osmolarity media and not in regenerating protoplasts. Mannan was the major hemicellulose detected in all tissues tested. Arabinogalactan proteins were detected in different cell types by different probes, consistent with structural heterogneity. The results reveal developmental and cell type specific differences in cell wall composition and provide a basis for analyzing cell wall phenotypes in knockout mutants.« less

Abdominal Wall Endometriosis Mimicking Metastases.

PubMed

Nambiar, Rakul; Anoop, T M; Mony, Rari P

2018-06-01

Abdominal wall lesions can be broadly divided into nontumorous and tumorous conditions. Nontumorous lesions include congenital lesion, abdominal wall hernia, inflammation and infection, vascular lesions, and miscellaneous conditions like hematoma. Tumorous lesions include benign and malignant neoplasms. Here, we report an unusual case of abdominal wall endometriosis mimicking metastases in a patient with breast carcinoma.

Xylem development and cell wall changes of soybean seedlings grown in space.

PubMed

de Micco, Veronica; Aronne, Giovanna; Joseleau, Jean-Paul; Ruel, Katia

2008-04-01

Plants growing in altered gravity conditions encounter changes in vascular development and cell wall deposition. The aim of this study was to investigate xylem anatomy and arrangement of cellulose microfibrils in vessel walls of different organs of soybean seedlings grown in Space. Seeds germinated and seedlings grew for 5 d in Space during the Foton-M2 mission. The environmental conditions, other than gravity, of the ground control repeated those experienced in orbit. The seedlings developed in space were compared with those of the control test on the basis of numerous anatomical and ultrastructural parameters such as number of veins, size and shape of vessel lumens, thickness of cell walls and deposition of cellulose microfibrils. Observations made with light, fluorescence and transmission electron microscopy, together with the quantification of the structural features through digital image analysis, showed that the alterations due to microgravity do not occur at the same level in the various organs of soybean seedlings. The modifications induced by microgravity or by the indirect effect of space-flight conditions, became conspicuous only in developing vessels at the ultrastructural level. The results suggested that the orientation of microfibrils and their assembly in developing vessels are perturbed by microgravity at the beginning of wall deposition, while they are still able to orient and arrange in thicker and ordered structures at later stages of secondary wall deposition. The process of proper cell-wall building, although not prevented, is perturbed in Space at the early stage of development. This would explain the almost unaltered anatomy of mature structures, accompanied by a slower growth observed in seedlings grown in Space than on Earth.

Xylem Development and Cell Wall Changes of Soybean Seedlings Grown in Space

PubMed Central

de Micco, Veronica; Aronne, Giovanna; Joseleau, Jean-Paul; Ruel, Katia

2008-01-01

Background and Aims Plants growing in altered gravity conditions encounter changes in vascular development and cell wall deposition. The aim of this study was to investigate xylem anatomy and arrangement of cellulose microfibrils in vessel walls of different organs of soybean seedlings grown in Space. Methods Seeds germinated and seedlings grew for 5 d in Space during the Foton-M2 mission. The environmental conditions, other than gravity, of the ground control repeated those experienced in orbit. The seedlings developed in space were compared with those of the control test on the basis of numerous anatomical and ultrastructural parameters such as number of veins, size and shape of vessel lumens, thickness of cell walls and deposition of cellulose microfibrils. Key Results Observations made with light, fluorescence and transmission electron microscopy, together with the quantification of the structural features through digital image analysis, showed that the alterations due to microgravity do not occur at the same level in the various organs of soybean seedlings. The modifications induced by microgravity or by the indirect effect of space-flight conditions, became conspicuous only in developing vessels at the ultrastructural level. The results suggested that the orientation of microfibrils and their assembly in developing vessels are perturbed by microgravity at the beginning of wall deposition, while they are still able to orient and arrange in thicker and ordered structures at later stages of secondary wall deposition. Conclusions The process of proper cell-wall building, although not prevented, is perturbed in Space at the early stage of development. This would explain the almost unaltered anatomy of mature structures, accompanied by a slower growth observed in seedlings grown in Space than on Earth. PMID:18252765

Non-lignified helical cell wall thickenings in root cortical cells of Aspleniaceae (Polypodiales): histology and taxonomical significance

PubMed Central

Leroux, O.; Bagniewska-Zadworna, A.; Rambe, S. K.; Knox, J. P.; Marcus, S. E.; Bellefroid, E.; Stubbe, D.; Chabbert, B.; Habrant, A.; Claeys, M.; Viane, R. L. L.

2011-01-01

Background and Aims Extraxylary helical cell wall thickenings in vascular plants are not well documented, except for those in orchid velamen tissues which have been studied extensively. Reports on their occurrence in ferns exist, but detailed information is missing. The aim of this study is to focus on the broad patterns of structure and composition and to study the taxonomic occurrence of helical cell wall thickenings in the fern family Aspleniaceae. Methods Structural and compositional aspects of roots have been examined by means of light, electron, epifluorescence and laser scanning confocal microscopy. To assess the taxonomical distribution of helical cell wall thickenings a molecular phylogenetic analysis based on rbcL sequences of 64 taxa was performed. Key Results The helical cell wall thickenings of all examined species showed considerable uniformity of design. The pattern consists of helical, regularly bifurcating and anastomosing strands. Compositionally, the cell wall thickenings were found to be rich in homogalacturonan, cellulose, mannan and xyloglucan. Thioacidolysis confirmed our negative phloroglucinol staining tests, demonstrating the absence of lignins in the root cortex. All taxa with helical cell wall thickenings formed a monophyletic group supported by a 100 % bootstrap value and composed of mainly epiphytic species. Conclusions This is the first report of non-lignified pectin-rich secondary cell walls in ferns. Based on our molecular analysis, we reject the hypothesis of parallel evolution of helical cell wall thickenings in Aspleniaceae. Helical cell wall thickenings can mechanically stabilize the cortex tissue, allowing maximal uptake of water and nutrients during rainfall events. In addition, it can also act as a boundary layer increasing the diffusive pathway towards the atmosphere, preventing desiccation of the stele of epiphytic growing species. PMID:21118842

Analysis of the vibration regimes of vascular walls

NASA Astrophysics Data System (ADS)

Kudryashov, A. V.; Rozenblyum, L. A.; Khurlapova, T. V.; Yakhno, V. G.

1980-11-01

The theoretical description exposed here can be used for explaining the differences which are sometimes observed between the values of the diastolic pressure derived from direct measurements and those derived from indirect measurements. Nervous and emotional action may alter markedly the mechanical properties of the muscular layer of the wall. In this respect it is important to what side the hysteresis loop in the radiusstress curve will be shifted. If the hysteresis is shifted towards the region of high pressures, then tones will be recorded at higher pi — P l values and, hence, the error in an indirect measurement of the pressure will increase. From this point of view the phenomenon of an "infinite tone" is explained by the dependence of the hysteresis of the radius on the stress on the wall in the pressure range Pdiast

Seasonal development of cambial activity in relation to xylem formation in Chinese fir.

PubMed

Wu, Hongyang; Xu, Huimin; Li, Hanyin; Wei, Dongmei; Lin, Jinxing; Li, Xiaojuan

2016-05-20

The vascular cambium is a lateral meristem which can differentiate into secondary phloem and xylem. The secondary growth of woody plants resulting from vascular cambium activity has been a focus of considerable attention, but the quantitative relationships between cambial activity and secondary xylem formation have been little studied. Our analysis of cytological changes in the cambium of Chinese fir (Cunninghamia lanceolata), revealed a significant positive correlation between vascular cambium cell numbers and cambium zone width through the seasonal cycle. Cambium cell numbers and the cambium cell radial diameter were closely related to xylem formation. Immuno-labeling showed that de-esterified homogalacturonan and (1-4)-β-d-galactan epitopes were highly abundant in cell walls of dormant-stage cambium, whereas high methylesterified homogalacturonan was strongly labeled in the active stage. Raman spectroscopy detected significant changes in the chemical composition of cell walls during the active-dormant stage transition. More pectin and less monolignols occurred in radial cell walls than in tangential walls during the dormant stage, but no significant changes were found in other stages, indicating that pectin accumulation facilitates cell wall expansion, with cambium activity transition. Our quantitative analysis of the relationship between cambial activity and xylem formation, as well as the cell wall modification during the active stage provides useful information about cambial characteristics and xylogenesis. Copyright © 2016. Published by Elsevier GmbH.

Vascular and antioxidant effects of an aqueous Mentha cordifolia extract in experimental N(G)-nitro-L-arginine methyl ester-induced hypertension.

PubMed

Pakdeechote, Poungrat; Prachaney, Parichat; Berkban, Warinee; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Khrisanapant, Wilaiwan; Phirawatthakul, Yada

2014-01-01

The effect of an aqueous Mentha cordifolia (MC) extract on the haemodynamic status, vascular remodeling, function, and oxidative status in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension was investigated. Male Sprague-Dawley rats were given L-NAME [50 mg/(kg body weight (BW) d)] in their drinking water for 5 weeks and were treated by intragastric administration with the MC extract [200 mg/(kgBWd)] for 2 consecutive weeks. Quercetin [25 mg/(kg BW d)] was used as a positive control. The effects of the MC extract on the haemodynamic status, thoracic aortic wall thickness, and oxidative stress markers were determined, and the vasorelaxant activity of the MC extract was tested in isolated mesenteric vascular beds in rats. Significant increases in the mean arterial pressure (MAP), heart rate (HR), hind limb vascular resistance (HVR), wall thickness, and cross-sectional area of the thoracic aorta, as well as oxidative stress markers were found in the L-NAME-treated group compared to the control (P < 0.05). MAP, HVR, wall thickness, cross-sectional area of the thoracic aorta, plasma malondialdehyde (MDA), and vascular superoxide anion production were significantly reduced in L-NAME hypersensitive rats treated with the MC extract or quercetin. Furthermore, the MC extract induced vasorelaxation in the pre-constricted mesenteric vascular bed with intact and denuded endothelium of normotensive and hypertensive rats. Our results suggest that the MC extract exhibits an antihypertensive effect via its antioxidant capacity, vasodilator property, and reduced vascular remodeling.

Arterial grafts exhibiting unprecedented cellular infiltration and remodeling in vivo: the role of cells in the vascular wall.

PubMed

Row, Sindhu; Peng, Haofan; Schlaich, Evan M; Koenigsknecht, Carmon; Andreadis, Stelios T; Swartz, Daniel D

2015-05-01

To engineer and implant vascular grafts in the arterial circulation of a pre-clinical animal model and assess the role of donor medial cells in graft remodeling and function. Vascular grafts were engineered using Small Intestinal Submucosa (SIS)-fibrin hybrid scaffold and implanted interpositionally into the arterial circulation of an ovine model. We sought to demonstrate implantability of SIS-Fibrin based grafts; examine the remodeling; and determine whether the presence of vascular cells in the medial wall was necessary for cellular infiltration from the host and successful remodeling of the implants. We observed no occlusions or anastomotic complications in 18 animals that received these grafts. Notably, the grafts exhibited unprecedented levels of host cell infiltration that was not limited to the anastomotic sites but occurred through the lumen as well as the extramural side, leading to uniform cell distribution. Incoming cells remodeled the extracellular matrix and matured into functional smooth muscle cells as evidenced by expression of myogenic markers and development of vascular reactivity. Interestingly, tracking the donor cells revealed that their presence was beneficial but not necessary for successful grafting. Indeed, the proliferation rate and number of donor cells decreased over time as the vascular wall was dominated by host cells leading to significant remodeling and development of contractile function. These results demonstrate that SIS-Fibrin grafts can be successfully implanted into the arterial circulation of a clinically relevant animal model, improve our understanding of vascular graft remodeling and raise the possibility of engineering mural cell-free arterial grafts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immuno and Affinity Cytochemical Analysis of Cell Wall Composition in the Moss Physcomitrella patens

DOE PAGES

Berry, Elizabeth A.; Tran, Mai L.; Dimos, Christos S.; ...

2016-03-08

In contrast to homeohydric vascular plants, mosses employ a poikilohydric strategy for surviving in the dry aerial environment. A detailed understanding of the structure, composition, and development of moss cell walls can contribute to our understanding of not only the evolution of overall cell wall complexity, but also the differences that have evolved in response to selection for different survival strategies. The model moss species Physcomitrella patens has a predominantly haploid lifecycle consisting of protonemal filaments that regenerate from protoplasts and enlarge by tip growth, and leafy gametophores composed of cells that enlarge by diffuse growth and differentiate into severalmore » different types. Advantages for genetic studies include methods for efficient targeted gene modification and extensive genomic resources. Immuno and affinity cytochemical labeling were used to examine the distribution of polysaccharides and proteins in regenerated protoplasts, protonemal filaments, rhizoids, and sectioned gametophores of P. patens. The cell wall composition of regenerated protoplasts was also characterized by flow cytometry. Crystalline cellulose was abundant in the cell walls of regenerating protoplasts and protonemal cells that developed on media of high osmolarity, whereas homogalactuonan was detected in the walls of protonemal cells that developed on low osmolarity media and not in regenerating protoplasts. Mannan was the major hemicellulose detected in all tissues tested. Arabinogalactan proteins were detected in different cell types by different probes, consistent with structural heterogneity. The results reveal developmental and cell type specific differences in cell wall composition and provide a basis for analyzing cell wall phenotypes in knockout mutants.« less

Comparative glycan profiling of Ceratopteris richardii ‘C-Fern’ gametophytes and sporophytes links cell-wall composition to functional specialization

PubMed Central

Eeckhout, Sharon; Leroux, Olivier; Willats, William G. T.; Popper, Zoë A.; Viane, Ronald L. L.

2014-01-01

Background and Aims Innovations in vegetative and reproductive characters were key factors in the evolutionary history of land plants and most of these transformations, including dramatic changes in life cycle structure and strategy, necessarily involved cell-wall modifications. To provide more insight into the role of cell walls in effecting changes in plant structure and function, and in particular their role in the generation of vascularization, an antibody-based approach was implemented to compare the presence and distribution of cell-wall glycan epitopes between (free-living) gametophytes and sporophytes of Ceratopteris richardii ‘C-Fern’, a widely used model system for ferns. Methods Microarrays of sequential diamino-cyclohexane-tetraacetic acid (CDTA) and NaOH extractions of gametophytes, spores and different organs of ‘C-Fern’ sporophytes were probed with glycan-directed monoclonal antibodies. The same probes were employed to investigate the tissue- and cell-specific distribution of glycan epitopes. Key Results While monoclonal antibodies against pectic homogalacturonan, mannan and xyloglucan widely labelled gametophytic and sporophytic tissues, xylans were only detected in secondary cell walls of the sporophyte. The LM5 pectic galactan epitope was restricted to sporophytic phloem tissue. Rhizoids and root hairs showed similarities in arabinogalactan protein (AGP) and xyloglucan epitope distribution patterns. Conclusions The differences and similarities in glycan cell-wall composition between ‘C-Fern’ gametophytes and sporophytes indicate that the molecular design of cell walls reflects functional specialization rather than genetic origin. Glycan epitopes that were not detected in gametophytes were associated with cell walls of specialized tissues in the sporophyte. PMID:24699895

Immuno and Affinity Cytochemical Analysis of Cell Wall Composition in the Moss Physcomitrella patens

PubMed Central

Berry, Elizabeth A.; Tran, Mai L.; Dimos, Christos S.; Budziszek, Michael J.; Scavuzzo-Duggan, Tess R.; Roberts, Alison W.

2016-01-01

In contrast to homeohydric vascular plants, mosses employ a poikilohydric strategy for surviving in the dry aerial environment. A detailed understanding of the structure, composition, and development of moss cell walls can contribute to our understanding of not only the evolution of overall cell wall complexity, but also the differences that have evolved in response to selection for different survival strategies. The model moss species Physcomitrella patens has a predominantly haploid lifecycle consisting of protonemal filaments that regenerate from protoplasts and enlarge by tip growth, and leafy gametophores composed of cells that enlarge by diffuse growth and differentiate into several different types. Advantages for genetic studies include methods for efficient targeted gene modification and extensive genomic resources. Immuno and affinity cytochemical labeling were used to examine the distribution of polysaccharides and proteins in regenerated protoplasts, protonemal filaments, rhizoids, and sectioned gametophores of P. patens. The cell wall composition of regenerated protoplasts was also characterized by flow cytometry. Crystalline cellulose was abundant in the cell walls of regenerating protoplasts and protonemal cells that developed on media of high osmolarity, whereas homogalactuonan was detected in the walls of protonemal cells that developed on low osmolarity media and not in regenerating protoplasts. Mannan was the major hemicellulose detected in all tissues tested. Arabinogalactan proteins were detected in different cell types by different probes, consistent with structural heterogneity. The results reveal developmental and cell type specific differences in cell wall composition and provide a basis for analyzing cell wall phenotypes in knockout mutants. PMID:27014284

Matrix Metalloproteinase 9 (MMP-9) Regulates Vein Wall Biomechanics in Murine Thrombus Resolution

PubMed Central

Nguyen, Khanh P.; McGilvray, Kirk C.; Puttlitz, Christian M.; Mukhopadhyay, Subhradip; Chabasse, Christine; Sarkar, Rajabrata

2015-01-01

Objective Deep venous thrombosis is a common vascular problem with long-term complications including post-thrombotic syndrome. Post-thrombotic syndrome consists of leg pain, swelling and ulceration that is related to incomplete or maladaptive resolution of the venous thrombus as well as loss of compliance of the vein wall. We examine the role of metalloproteinase-9 (MMP-9), a gene important in extracellular remodeling in other vascular diseases, in mediating thrombus resolution and biomechanical changes of the vein wall. Methods and Results The effects of targeted deletion of MMP-9 were studied in an in vivo murine model of thrombus resolution using the FVB strain of mice. MMP-9 expression and activity significantly increased on day 3 after DVT. The lack of MMP-9 impaired thrombus resolution by 27% and this phenotype was rescued by the transplantation of wildtype bone marrow cells. Using novel biomechanical techniques, we demonstrated that the lack of MMP-9 significantly decreased thrombus-induced loss of vein wall compliance. Biomechanical analysis of the contribution of individual structural components showed that MMP-9 affected the elasticity of the extracellular matrix and collagen-elastin fibers. Biochemical and histological analyses correlated with these biomechanical effects as thrombi of mice lacking MMP-9 had significantly fewer macrophages and collagen as compared to those of wildtype mice. Conclusions MMP-9 mediates thrombus-induced loss of vein wall compliance by increasing stiffness of the extracellular matrix and collagen-elastin fibers during thrombus resolution. MMP-9 also mediates macrophage and collagen content of the resolving thrombus and bone-marrow derived MMP-9 plays a role in resolution of thrombus mass. These disparate effects of MMP-9 on various aspects of thrombus illustrate the complexity of individual protease function on biomechanical and morphometric aspects of thrombus resolution. PMID:26406902

Analysis of gene expression profiles for cell wall modifying proteins and ACC synthases in soybean cyst nematode colonized roots, adventitious rooting hypocotyls, root tips, flooded roots, and IBA and ACC treatment roots

USDA-ARS?s Scientific Manuscript database

We hypothesized that soybean cyst nematode (SCN) co-opts a part or all of one or more innate developmental process in soybean to establish its feeding structure, syncytium, in soybean roots. The syncytium in soybean roots is formed in a predominantly lateral direction within the vascular bundle by ...

Plant metabolism and cell wall formation in space (microgravity) and on Earth

NASA Technical Reports Server (NTRS)

Lewis, Norman G.

1994-01-01

Variations in cell wall chemistry provide vascular plants with the ability to withstand gravitational forces, as well as providing facile mechanisms for correctional responses to various gravitational stimuli, e.g., in reaction wood formation. A principal focus of our current research is to precisely and systematically dissect the essentially unknown mechanism(s) of vascular plant cell wall assembly, particularly with respect to formation of its phenolic constituents, i.e., lignins and suberins, and how gravity impacts upon these processes. Formation of these phenolic polymers is of particular interest, since it appears that elaboration of their biochemical pathways was essential for successful land adaptation. By extrapolation, we are also greatly intrigued as to how the microgravity environment impacts upon 'normal' cell wall assembly mechanisms/metabolism.

[Hemodynamic phenomena in retrobulhar and eyeball vessels].

PubMed

Modrzejewska, Monika

2011-01-01

The purpose of this review was to evaluate factors connected with blood flow and indices regulating vascular diameter and some parameters influencing retrobulbar circulation such as type of vascular resistance, anatomical structure of vascular wall and vessel lumen. Neurogenic and angiogenic factors, rheological blood composition, presence of anatomical and pathological obstructions on blood flow pathway as well as degree of development of collateral circulation pathways--have influence on the volume and blood flow velocity in eyeball. There were discussed bulbar circulation hemodynamics, emphasizing the importance of perfusion pressure. The role of risk factors was underlined for pathological lesions in vessels supplying blood to eyeball and in ophthalmic artery (OA) and its collaterals, in central retinal artery (CRA) as well as posterior ciliary arteries (PCAs), and in venous system carrying away blood from eye. IN CONCLUSION--the results of many studies of retrobulbar blood flow in different types of ophthalmic diseases of the vascular etiopathogenesis indicate that registry of the mean values of blood flow parameters and vascular resistance indices parallel to measurement of blood flow spectrum in OA, CRA, PCAs arteries, might contribute much information to explain or to evaluate nature of pathological changes in retinal and choroidal circulation.

Simulation of blood flow in deformable vessels using subject-specific geometry and spatially varying wall properties

PubMed Central

Xiong, Guanglei; Figueroa, C. Alberto; Xiao, Nan; Taylor, Charles A.

2011-01-01

SUMMARY Simulation of blood flow using image-based models and computational fluid dynamics has found widespread application to quantifying hemodynamic factors relevant to the initiation and progression of cardiovascular diseases and for planning interventions. Methods for creating subject-specific geometric models from medical imaging data have improved substantially in the last decade but for many problems, still require significant user interaction. In addition, while fluid–structure interaction methods are being employed to model blood flow and vessel wall dynamics, tissue properties are often assumed to be uniform. In this paper, we propose a novel workflow for simulating blood flow using subject-specific geometry and spatially varying wall properties. The geometric model construction is based on 3D segmentation and geometric processing. Variable wall properties are assigned to the model based on combining centerline-based and surface-based methods. We finally demonstrate these new methods using an idealized cylindrical model and two subject-specific vascular models with thoracic and cerebral aneurysms. PMID:21765984

Modifying lignin to improve bioenergy feedstocks: strengthening the barrier against pathogens?†

PubMed Central

Sattler, Scott E.; Funnell-Harris, Deanna L.

2013-01-01

Lignin is a ubiquitous polymer present in cell walls of all vascular plants, where it rigidifies and strengthens the cell wall structure through covalent cross-linkages to cell wall polysaccharides. The presence of lignin makes the cell wall recalcitrant to conversion into fermentable sugars for bioenergy uses. Therefore, reducing lignin content and modifying its linkages have become major targets for bioenergy feedstock development through either biotechnology or traditional plant breeding. In addition, lignin synthesis has long been implicated as an important plant defense mechanism against pathogens, because lignin synthesis is often induced at the site of pathogen attack. This article explores the impact of lignin modifications on the susceptibility of a range of plant species to their associated pathogens, and the implications for development of feedstocks for the second-generation biofuels industry. Surprisingly, there are some instances where plants modified in lignin synthesis may display increased resistance to associated pathogens, which is explored in this article. PMID:23577013

Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall.

PubMed

Araos, Patricio; Mondaca, David; Jalil, Jorge E; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz

2016-12-01

Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague-Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p < 0.05) compared with control rats. All treatments reduced ROCK activation in the aortic wall to control levels (p < 0.05). Besides, significantly increased protein levels of transforming growth factor β1 (TGF-β 1 ), gene expression of TGF-β 1 , connective tissue growth factor (CTGF), p22 phox and gp91 phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as well as increased media thickness and aortic media area/lumen area (AM/LA) in the untreated hypertensive rats were significantly reduced (p < 0.05) to control levels by all treatments. Similar effects were observed using both diuretics alone or in combination with FAS. In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients. © The Author(s), 2016.

Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall

PubMed Central

Araos, Patricio; Mondaca, David; Jalil, Jorge E.; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz

2016-01-01

Background: Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. Methods: Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague–Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. Results: All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p < 0.05) compared with control rats. All treatments reduced ROCK activation in the aortic wall to control levels (p < 0.05). Besides, significantly increased protein levels of transforming growth factor β1 (TGF-β1), gene expression of TGF-β1, connective tissue growth factor (CTGF), p22 phox and gp91 phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as well as increased media thickness and aortic media area/lumen area (AM/LA) in the untreated hypertensive rats were significantly reduced (p < 0.05) to control levels by all treatments. Similar effects were observed using both diuretics alone or in combination with FAS. Conclusions: In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients. PMID:27587602

Formation of the peak amplitude of blood flow oscillations at a frequency of 0.1 Hz in the human cardiovascular system by the noise effect on the heart

NASA Astrophysics Data System (ADS)

Grinevich, Andrey A.; Tankanag, Arina V.; Chemeris, Nikolay K.

2017-04-01

In the framework of our previous hypothesis about the participation of structural and hydrodynamic properties of the vascular bed in the formation of the 0.1-Hz component of blood flow oscillations in the human cardiovascular system and on the basis of the reduced hydrodynamic model, the role of additive stochastic perturbations of the operation of the single-chamber pump that simulates the heart was investigated. It was shown that aperiodic noise modulation of the rigidity of the walls of the pump or its valves generates low-frequency oscillations of pressure of arterial vascular bed with the spectral components at a frequency close to 0.1 Hz.

Non-invasive optical modulation of local vascular permeability

NASA Astrophysics Data System (ADS)

Choi, Myunghwan; Choi, Chulhee

2011-03-01

For a systemically administered drug to act, it first needs to cross the vascular wall. This step represents a bottleneck for drug development, especially in the brain or retina, where tight junctions between endothelial cells form physiological barriers. Here, we demonstrate that femtosecond pulsed laser irradiation focused on the blood vessel wall induces transient permeabilization of plasma. Nonlinear absorption of the pulsed laser enabled the noninvasive modulation of vascular permeability with high spatial selectivity in three dimensions. By combining this method with systemic injection, we could locally deliver molecular probes in various tissues, such as brain cortex, meninges, ear, striated muscle, and bone. We suggest this method as a novel delivery tool for molecular probes or drugs.

Endothelial dysfunction and amyloid-β-induced neurovascular alterations

PubMed Central

Koizumi, Kenzo; Wang, Gang; Park, Laibaik

2015-01-01

Alzheimer's disease (AD) and cerebrovascular diseases share common vascular risk factors that have disastrous effects on cerebrovascular regulation. Endothelial cells, lining inner walls of cerebral blood vessels, form a dynamic interface between the blood and the brain and are critical for the maintenance of neurovascular homeostasis. Accordingly, injury in endothelial cells is regarded as one of the earliest symptoms of impaired vasoregulatory mechanisms. Extracellular buildup of amyloid-β (Aβ) is a central pathogenic factor in AD. Aβ exerts potent detrimental effects on cerebral blood vessels and impairs endothelial structure and function. Recent evidence implicates vascular oxidative stress and activation of the nonselective cationic channel transient receptor potential melastatin (TRPM)-2 on endothelial cells in the mechanisms of Aβ-induced neurovascular dysfunction. Thus, Aβ triggers opening of TRPM2 channels in endothelial cells leading to intracellular Ca2+ overload and vasomotor dysfunction. The cerebrovascular dysfunction may contribute to AD pathogenesis by reducing the cerebral blood supply, leading to increased susceptibility to vascular insufficiency, and by promoting Aβ accumulation. The recent realization that vascular factors contribute to AD pathobiology suggests new targets for the prevention and treatment of this devastating disease. PMID:26328781

Markers of Vascular Perturbation Correlate with Airway Structural Change in Asthma

PubMed Central

Kruger, Stanley J.; Schiebler, Mark L.; Evans, Michael D.; Sorkness, Ronald L.; Denlinger, Loren C.; Busse, William W.; Jarjour, Nizar N.; Montgomery, Robert R.; Mosher, Deane F.; Fain, Sean B.

2013-01-01

Rationale: Air trapping and ventilation defects on imaging are characteristics of asthma. Airway wall thickening occurs in asthma and is associated with increased bronchial vascularity and vascular permeability. Vascular endothelial cell products have not been explored as a surrogate to mark structural airway changes in asthma. Objectives: Determine whether reporters of vascular endothelial cell perturbation correlate with airway imaging metrics in patients with asthma of varying severity. Methods: Plasma from Severe Asthma Research Program subjects was analyzed by ELISAs for soluble von Willebrand factor mature protein (VWF:Ag) and propeptide (VWFpp), P-selectin, and platelet factor 4. Additional subjects were analyzed over 48 hours after whole-lung antigen challenge. We calculated ventilation defect volume by hyperpolarized helium-3 magnetic resonance imaging and areas of low signal density by multidetector computed tomography (less than −856 Hounsfield units [HU] at functional residual capacity and −950 HU at total lung capacity [TLC]). Measurements and Main Results: VWFpp and VWFpp/Ag ratio correlated with and predicted greater percentage defect volume on hyperpolarized helium-3 magnetic resonance imaging. P-selectin correlated with and predicted greater area of low density on chest multidetector computed tomography less than −950 HU at TLC. Platelet factor 4 did not correlate. Following whole-lung antigen challenge, variation in VWFpp, VWFpp/Ag, and P-selectin among time-points was less than that among subjects, indicating stability and repeatability of the measurements. Conclusions: Plasma VWFpp and P-selectin may be useful as surrogates of functional and structural defects that are evident on imaging. The results raise important questions about why VWFpp and P-selectin are associated specifically with different imaging abnormalities. PMID:23855693

Distinctions in manifestation of the hemorrhagic syndrome related to chronic, long-term and acute irradiation. [Rats;. gamma. rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arlashchenko, N.I.; Gorlov, V.G.; Maksimova, E.N.

Two phenomena, decrease in strength of the vascular wall and decreased amount of thrombocytes in blood, must coincide for manifestation of the hemorrhagic syndrome. Either almost simultaneous injury to the vascular wall and thrombocyte function (with acute irradiation) or dissociation of these two processes (with long-term irradiation) may be observed, depending on the radiation dose. Chronic exposure at low (subliminal) dose rates does not elicit hemorrhagic manifestations or death of rats due to pathological bleeding.

Coagulating activity of the blood, vascular wall, and myocardium under hypodynamia conditions

NASA Technical Reports Server (NTRS)

Petrovskiy, B. V. (Editor); Chazov, E. I. (Editor); Andreyev, S. V. (Editor)

1980-01-01

In order to study the effects of hypodynamia on the coagulating properties of the blood, vascular wall, and myocardium, chinchilla rabbits were kept for varying periods in special cages which restricted their movements. At the end of the experiment, blood samples were taken and the animals were sacrificed. Preparations were made from the myocardium venae cavae, and layers of the aorta. Two resultant interrelated and mutually conditioned syndromes were discovered: thrombohemorrhagic in the blood and hemorrago-thrombotic in the tissues.

Histological and three dimensional organizations of lymphoid tubules in normal lymphoid organ of Penaeus monodon.

PubMed

Duangsuwan, Pornsawan; Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Wanichanon, Chaitip; Sobhon, Prasert

2008-04-01

The normal lymphoid organ of Penaeus monodon (which tested negative for WSSV and YHV) was composed of two parts: lymphoid tubules and interstitial spaces, which were permeated with haemal sinuses filled with large numbers of haemocytes. There were three permanent types of cells present in the wall of lymphoid tubules: endothelial, stromal and capsular cells. Haemocytes penetrated the endothelium of the lymphoid tubule's wall to reside among the fixed cells. The outermost layer of the lymphoid tubule was covered by a network of fibers embedded in a PAS-positive extracellular matrix, which corresponded to a basket-like network that covered all the lymphoid tubules as visualized by a scanning electron microscope (SEM). Argyrophilic reticular fibers surrounded haemal sinuses and lymphoid tubules. Together they formed the scaffold that supported the lymphoid tubule. Using vascular cast and SEM, the three dimensional structure of the subgastric artery that supplies each lobe of the lymphoid organ was reconstructed. This artery branched into highly convoluted and blind-ending terminal capillaries, each forming the lumen of a lymphoid tubule around which haemocytes and other cells aggregated to form a cuff-like wall. Stromal cells which form part of the tubular scaffold were immunostained for vimentin. Examination of the whole-mounted lymphoid organ, immunostained for vimentin, by confocal microscopy exhibited the highly branching and convoluted lymphoid tubules matching the pattern of the vascular cast observed in SEM.

"One-stop-shop" ultrasound diagnosis of functional, structural and physicomechanical properties of the brachial artery.

PubMed

Balzer, J; Boos, M; Rassaf, T; Heiss, Ch; Preik, M; Matern, S; Schoebel, F; Kelm, M; Lauer, T

2007-05-01

The pathogenesis of atherosclerosis comprises endothelial dysfunction, thickening as well as impaired compliance of the arterial vessel wall. Early assessment of these alterations of the vessel wall at the same site of the vascular tree has yet been hampered by the lack of highly sensitive diagnostic approaches suitable for clinical routine. We therefore aimed to develop and validate a single non-invasive examination of the brachial artery for simultaneous and highly accurate measurement of functional, structural and physicomechanical parameters of the brachial artery. 20 healthy individuals were investigated using high resolution ultrasound. Flow-mediated dilation (FMD), fractional diameter changes (FDC) and intima-media-thickness (IMT) were measured in the same segment of the brachial artery. Coefficients of variation, day-to-day-variability, between- and within-observer-variability were investigated in 5 individuals. All measurements were performed manually and by an automated PC-based analyzing system. Mean values for all measured parameters were 7.65 +/- 0.8% for FMD, 0.02 +/- 0.002 for FDC, 0.351 +/- 0.007 mm for IMT and followed an even distribution throughout the study population. Automated analysis of coefficient of variation, day-to-day-, between- and within-observer variabilities were: 0. 78%, 1.3%, 0.8%, 0.8% (FMD); 4.7%, 2.8%, 4.2%, 2.7% (FDC); 1.8%, 1.1%, 1.9%, 1.1% (IMT). Coefficient of variation, day-to-day-, between- and within-observer variabilities for the manual readings were significantly higher. Functional, structural and physicomechanical parameters of the brachial artery can be quantified consecutively, time-saving and highly reproducibly as an "one-stop-shop" in a single session using high resolution ultrasound with digitized post-processing. This highlights the future possibility of early, sensitive and non-invasive diagnostic testing of vascular function in patients prone to vascular disease.

Use of the omentum in chest-wall reconstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fix, R.J.; Vasconez, L.O.

1989-10-01

Increased use of the omentum in chest-wall reconstruction has paralleled the refinement of anatomic knowledge and the development of safe mobilization techniques. Important anatomic points are the omental attachments to surrounding structures, the major blood supply from the left and right gastroepiploic vessels, and the collateral circulation via the gastroepiploic arch and Barkow's marginal artery. Mobilization of the omentum to the thorax involves division of its attachments to the transverse colon and separation from the greater curvature to fabricate a bipedicled flap. Most anterior chest wounds and virtually all mediastinal wounds can be covered with the omentum based on bothmore » sets of gastroepiploic vessels. The arc of transposition is increased when the omentum is based on a single pedicle, allowing coverage of virtually all chest-wall defects. The final method of increasing flap length involves division of the gastroepiploic arch and reliance on Barkow's marginal artery as collateral circulation to maintain flap viability. With regard to chest-wall reconstruction, we have included the omentum in the armamentarium of flaps used to cover mediastinal wounds. The omentum is our flap of choice for the reconstruction of most radiation injuries of the chest wall. The omentum may also be used to provide protection to visceral anastomoses, vascular conduits, and damaged structures in the chest, as well as to cover defects secondary to tumor excision or trauma. In brief, the omentum has proved to be a most dependable and versatile flap, particularly applicable to chest-wall reconstruction.« less

Development and characterization of hybrid tubular structure of PLCL porous scaffold with hMSCs/ECs cell sheet.

PubMed

Pangesty, Azizah Intan; Arahira, Takaaki; Todo, Mitsugu

2017-09-15

Tissue engineering offers an alternate approach to providing vascular graft with potential to grow similar with native tissue by seeding autologous cells into biodegradable scaffold. In this study, we developed a combining technique by layering a sheet of cells onto a porous tubular scaffold. The cell sheet prepared from co-culturing human mesenchymal stem cells (hMSCs) and endothelial cells (ECs) were able to infiltrate through porous structure of the tubular poly (lactide-co-caprolactone) (PLCL) scaffold and further proliferated on luminal wall within a week of culture. Moreover, the co-culture cell sheet within the tubular scaffold has demonstrated a faster proliferation rate than the monoculture cell sheet composed of MSCs only. We also found that the co-culture cell sheet expressed a strong angiogenic marker, including vascular endothelial growth factor (VEGF) and its receptor (VEGFR), as compared with the monoculture cell sheet within 2 weeks of culture, indicating that the co-culture system could induce differentiation into endothelial cell lineage. This combined technique would provide cellularization and maturation of vascular construct in relatively short period with a strong expression of angiogenic properties.

Edaravone enhances the viability of ischemia/reperfusion flaps.

PubMed

Zhang, Dong-Yi; Kang, Shen-Song; Zhang, Zheng-Wen; Wu, Rui

2017-02-01

The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion (IR) and its mechanism. Forty-eight adult male SD rats were randomly divided into 3 groups: control group (n=16), IR group (n=16), and edaravone-treated IR group (n=16). An island flap at left lower abdomen (6.0 cm×3.0 cm in size), fed by the superficial epigastric artery and vein, was created in each rat of all the three groups. The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h, and then the blood perfusion was restored. From 15 min before reperfusion, rats in the edaravone-treated IR group were intraperitoneally injected with edaravone (10 mg/kg), once every 12 h, for 3 days. Rats in the IR group and control group were intraperitoneally injected with saline, with the same method and frequency as the rats in the edaravone-treated IR group. In IR group and edaravone-treated IR group, samples of flaps were harvested after reperfusion of the flaps for 24 h. In the control group, samples of flaps were harvested 34 h after creation of the flaps. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined, and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin (HE) staining, apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and the apoptotic rate of cells in vascular wall was calculated. The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy (TEM). Seven days after the operation, we calculated the flap viability of each group, and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels. The results showed that the content of MDA, the number of multicore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group. The activity of SOD, flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group. All the differences were statistically significant. The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group. It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels, which is related to scavenging oxygen free radicals, reducing the consumption of SOD, reducing the extent of lipid peroxidation and inflammation, and protecting functional structure of vessels in the early stages of reperfusion.

Lignin Down-regulation of Zea mays via dsRNAi and Klason Lignin Analysis

PubMed Central

Park, Sang-Hyuck; Ong, Rebecca Garlock; Mei, Chuansheng; Sticklen, Mariam

2014-01-01

To facilitate the use of lignocellulosic biomass as an alternative bioenergy resource, during biological conversion processes, a pretreatment step is needed to open up the structure of the plant cell wall, increasing the accessibility of the cell wall carbohydrates. Lignin, a polyphenolic material present in many cell wall types, is known to be a significant hindrance to enzyme access. Reduction in lignin content to a level that does not interfere with the structural integrity and defense system of the plant might be a valuable step to reduce the costs of bioethanol production. In this study, we have genetically down-regulated one of the lignin biosynthesis-related genes, cinnamoyl-CoA reductase (ZmCCR1) via a double stranded RNA interference technique. The ZmCCR1_RNAi construct was integrated into the maize genome using the particle bombardment method. Transgenic maize plants grew normally as compared to the wild-type control plants without interfering with biomass growth or defense mechanisms, with the exception of displaying of brown-coloration in transgenic plants leaf mid-ribs, husks, and stems. The microscopic analyses, in conjunction with the histological assay, revealed that the leaf sclerenchyma fibers were thinned but the structure and size of other major vascular system components was not altered. The lignin content in the transgenic maize was reduced by 7-8.7%, the crystalline cellulose content was increased in response to lignin reduction, and hemicelluloses remained unchanged. The analyses may indicate that carbon flow might have been shifted from lignin biosynthesis to cellulose biosynthesis. This article delineates the procedures used to down-regulate the lignin content in maize via RNAi technology, and the cell wall compositional analyses used to verify the effect of the modifications on the cell wall structure. PMID:25080235

Lignin down-regulation of Zea mays via dsRNAi and klason lignin analysis.

PubMed

Park, Sang-Hyuck; Ong, Rebecca Garlock; Mei, Chuansheng; Sticklen, Mariam

2014-07-23

To facilitate the use of lignocellulosic biomass as an alternative bioenergy resource, during biological conversion processes, a pretreatment step is needed to open up the structure of the plant cell wall, increasing the accessibility of the cell wall carbohydrates. Lignin, a polyphenolic material present in many cell wall types, is known to be a significant hindrance to enzyme access. Reduction in lignin content to a level that does not interfere with the structural integrity and defense system of the plant might be a valuable step to reduce the costs of bioethanol production. In this study, we have genetically down-regulated one of the lignin biosynthesis-related genes, cinnamoyl-CoA reductase (ZmCCR1) via a double stranded RNA interference technique. The ZmCCR1_RNAi construct was integrated into the maize genome using the particle bombardment method. Transgenic maize plants grew normally as compared to the wild-type control plants without interfering with biomass growth or defense mechanisms, with the exception of displaying of brown-coloration in transgenic plants leaf mid-ribs, husks, and stems. The microscopic analyses, in conjunction with the histological assay, revealed that the leaf sclerenchyma fibers were thinned but the structure and size of other major vascular system components was not altered. The lignin content in the transgenic maize was reduced by 7-8.7%, the crystalline cellulose content was increased in response to lignin reduction, and hemicelluloses remained unchanged. The analyses may indicate that carbon flow might have been shifted from lignin biosynthesis to cellulose biosynthesis. This article delineates the procedures used to down-regulate the lignin content in maize via RNAi technology, and the cell wall compositional analyses used to verify the effect of the modifications on the cell wall structure.

β-1,3-Glucans are components of brown seaweed (Phaeophyceae) cell walls.

PubMed

Raimundo, Sandra Cristina; Pattathil, Sivakumar; Eberhard, Stefan; Hahn, Michael G; Popper, Zoë A

2017-03-01

LAMP is a cell wall-directed monoclonal antibody (mAb) that recognizes a β-(1,3)-glucan epitope. It has primarily been used in the immunolocalization of callose in vascular plant cell wall research. It was generated against a brown seaweed storage polysaccharide, laminarin, although it has not often been applied in algal research. We conducted in vitro (glycome profiling of cell wall extracts) and in situ (immunolabeling of sections) studies on the brown seaweeds Fucus vesiculosus (Fucales) and Laminaria digitata (Laminariales). Although glycome profiling did not give a positive signal with the LAMP mAb, this antibody clearly detected the presence of the β-(1,3)-glucan in situ, showing that this epitope is a constituent of these brown algal cell walls. In F. vesiculosus, the β-(1,3)-glucan epitope was present throughout the cell walls in all thallus parts; in L. digitata, the epitope was restricted to the sieve plates of the conductive elements. The sieve plate walls also stained with aniline blue, a fluorochrome used as a probe for callose. Enzymatic digestion with an endo-β-(1,3)-glucanase removed the ability of the LAMP mAb to label the cell walls. Thus, β-(1,3)-glucans are structural polysaccharides of F. vesiculosus cell walls and are integral components of the sieve plates in these brown seaweeds, reminiscent of plant callose.

Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 Regulates Xylem Development and Growth by a Conserved Mechanism That Modulates Hormone Signaling1[W][OPEN

PubMed Central

Grienenberger, Etienne; Douglas, Carl J.

2014-01-01

Despite a strict conservation of the vascular tissues in vascular plants (tracheophytes), our understanding of the genetic basis underlying the differentiation of secondary cell wall-containing cells in the xylem of tracheophytes is still far from complete. Using coexpression analysis and phylogenetic conservation across sequenced tracheophyte genomes, we identified a number of Arabidopsis (Arabidopsis thaliana) genes of unknown function whose expression is correlated with secondary cell wall deposition. Among these, the Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 (VUP1) gene encodes a predicted protein of 24 kD with no annotated functional domains but containing domains that are highly conserved in tracheophytes. Here, we show that the VUP1 expression pattern, determined by promoter-β-glucuronidase reporter gene expression, is associated with vascular tissues, while vup1 loss-of-function mutants exhibit collapsed morphology of xylem vessel cells. Constitutive overexpression of VUP1 caused dramatic and pleiotropic developmental defects, including severe dwarfism, dark green leaves, reduced apical dominance, and altered photomorphogenesis, resembling brassinosteroid-deficient mutants. Constitutive overexpression of VUP homologs from multiple tracheophyte species induced similar defects. Whole-genome transcriptome analysis revealed that overexpression of VUP1 represses the expression of many brassinosteroid- and auxin-responsive genes. Additionally, deletion constructs and site-directed mutagenesis were used to identify critical domains and amino acids required for VUP1 function. Altogether, our data suggest a conserved role for VUP1 in regulating secondary wall formation during vascular development by tissue- or cell-specific modulation of hormone signaling pathways. PMID:24567189

Comparative glycan profiling of Ceratopteris richardii 'C-Fern' gametophytes and sporophytes links cell-wall composition to functional specialization.

PubMed

Eeckhout, Sharon; Leroux, Olivier; Willats, William G T; Popper, Zoë A; Viane, Ronald L L

2014-10-01

Innovations in vegetative and reproductive characters were key factors in the evolutionary history of land plants and most of these transformations, including dramatic changes in life cycle structure and strategy, necessarily involved cell-wall modifications. To provide more insight into the role of cell walls in effecting changes in plant structure and function, and in particular their role in the generation of vascularization, an antibody-based approach was implemented to compare the presence and distribution of cell-wall glycan epitopes between (free-living) gametophytes and sporophytes of Ceratopteris richardii 'C-Fern', a widely used model system for ferns. Microarrays of sequential diamino-cyclohexane-tetraacetic acid (CDTA) and NaOH extractions of gametophytes, spores and different organs of 'C-Fern' sporophytes were probed with glycan-directed monoclonal antibodies. The same probes were employed to investigate the tissue- and cell-specific distribution of glycan epitopes. While monoclonal antibodies against pectic homogalacturonan, mannan and xyloglucan widely labelled gametophytic and sporophytic tissues, xylans were only detected in secondary cell walls of the sporophyte. The LM5 pectic galactan epitope was restricted to sporophytic phloem tissue. Rhizoids and root hairs showed similarities in arabinogalactan protein (AGP) and xyloglucan epitope distribution patterns. The differences and similarities in glycan cell-wall composition between 'C-Fern' gametophytes and sporophytes indicate that the molecular design of cell walls reflects functional specialization rather than genetic origin. Glycan epitopes that were not detected in gametophytes were associated with cell walls of specialized tissues in the sporophyte. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multiple roles of connexins in atherosclerosis- and restenosis-induced vascular remodelling.

PubMed

Morel, Sandrine

2014-01-01

Endothelial dysfunction is the initial step in atherosclerotic plaque development in large- and medium-sized arteries. This progressive disease, which starts during childhood, is characterized by the accumulation of lipids, macrophages, neutrophils, T lymphocytes and smooth muscle cells in the intima of the vessels. Erosion and rupture of the atherosclerotic plaque may induce myocardial infarction and cerebrovascular accidents, which are responsible for a large percentage of sudden deaths. The most common treatment for atherosclerosis is angioplasty and stent implantation, but these surgical interventions favour a vascular reaction called restenosis and the associated de-endothelialization increases the risk of thrombosis. This review provides an overview of the role of connexins, a large family of transmembrane proteins, in vascular remodelling associated with atherosclerosis and restenosis. The connexins expressed in the vascular wall are Cx37, Cx40, Cx43 and Cx45; their expressions vary with vascular territory and species. Connexins form hemichannels or gap junction channels, allowing the exchange of ions and small metabolites between the cytosol and extracellular space or between neighbouring cells, respectively. Connexins have important roles in vascular physiology; they support radial and longitudinal cell-to-cell communication in the vascular wall, and significant changes in their expression patterns have been described during atherosclerosis and restenosis.

Oxidative stress induces gastric submucosal arteriolar dysfunction in the elderly

PubMed Central

Liu, Lei; Liu, Yan; Cui, Jie; Liu, Hong; Liu, Yan-Bing; Qiao, Wei-Li; Sun, Hong; Yan, Chang-Dong

2013-01-01

AIM: To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process. METHODS: Twenty male patients undergoing subtotal gastrectomy were enrolled in this study. Young and elderly patient groups aged 25-40 years and 60-85 years, respectively, were included. Inclusion criteria were: no clinical evidence of cardiovascular, renal or diabetic diseases. Conventional clinical examinations were carried out. After surgery, gastric submucosal arteries were immediately dissected free of fat and connective tissue. Vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured by isolated vascular perfusion. Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin (HE) staining and Verhoeff van Gieson (EVG) staining. The expression of xanthine oxidase (XO) and manganese-superoxide dismutase (Mn-SOD) was assessed by Western blotting analysis. The malondialdehyde (MDA) and hydrogen peroxide (H2O2) content and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined according to commercial kits. RESULTS: The overall structure of vessel walls was shown by HE and EVG staining, respectively. Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients; however, cell layer number in the vessel wall increased significantly in the elderly group. Compared with submucosal arteries in young patients, the amount of vascular collagen fibers, lumen diameter and media cross-sectional area were significantly increased in elderly patients. Ach- and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients. Compared with the young group, the expression of XO and the contents of MDA and H2O2 in gastric submucosal arterioles were increased in the elderly group. In addition, the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young group. CONCLUSION: Gastric vascular dysfunction and senescence may be associated with increased oxidative stress and decreased antioxidative defense in the aging process. PMID:24409074

Hyperhomocysteinemia. An emerging and important risk factor for thromboembolic and cardiovascular disease.

PubMed

Guba, S C; Fink, L M; Fonseca, V

1996-12-01

Homocysteine is an important contributing factor to thrombosis, vascular injury, and vascular disease. Mechanisms for homocysteine-induced vascular disease include alterations in coagulation as well as endothelial cell and vessel wall injury. Hyperhomocysteinemia (HH[e]) can occur when homocysteine metabolism is altered by mutations in enzymes responsible for homocysteine metabolism. Characterization of these mutations identifies patient groups at risk for vascular disease. Treatment of HH(e) consists of vitamins and raises the possibility that some forms of vascular disease may be easily, safely, and inexpensively treated.

Role of reactive oxygen and nitrogen species in the vascular responses to inflammation

PubMed Central

Kvietys, Peter R.; Granger, D. Neil

2012-01-01

Inflammation is a complex and potentially life-threatening condition that involves the participation of a variety of chemical mediators, signaling pathways, and cell types. The microcirculation, which is critical for the initiation and perpetuation of an inflammatory response, exhibits several characteristic functional and structural changes in response to inflammation. These include vasomotor dysfunction (impaired vessel dilation and constriction), the adhesion and transendothelial migration of leukocytes, endothelial barrier dysfunction (increased vascular permeability), blood vessel proliferation (angiogenesis), and enhanced thrombus formation. These diverse responses of the microvasculature largely reflect the endothelial cell dysfunction that accompanies inflammation and the central role of these cells in modulating processes as varied as blood flow regulation, angiogenesis, and thrombogenesis. The importance of endothelial cells in inflammation-induced vascular dysfunction is also predicated on the ability of these cells to produce and respond to reactive oxygen and nitrogen species. Inflammation seems to upset the balance between nitric oxide and superoxide within (and surrounding) endothelial cells, which is necessary for normal vessel function. This review is focused on defining the molecular targets in the vessel wall that interact with reactive oxygen species and nitric oxide to produce the characteristic functional and structural changes that occur in response to inflammation. This analysis of the literature is consistent with the view that reactive oxygen and nitrogen species contribute significantly to the diverse vascular responses in inflammation and supports efforts that are directed at targeting these highly reactive species to maintain normal vascular health in pathological conditions that are associated with acute or chronic inflammation. PMID:22154653

[Proposed model of vascular trauma by mean of mechanical characterization of endovascular prostheses (stents) based on structural analysis by FEA].

PubMed

Bustamante, John; Uribe, Pablo; Sosa, Mauricio; Valencia, Raúl

2016-01-01

The accumulated evidence on angioplasty techniques with stents has raised a controversy about the factors that influence the final vascular response. Indeed, several studies have shown there might be re-stenosis between 30% to 40% about 6 months after placement, relating to the design of the device as one of the main causes. This paper proposes the functional characterization of endovascular stents, analyzing its mechanical influence in the vascular system and predicting implicit traumatic factors in the vessel. A structural analysis was made for several computational models of endovascular stents using Finite Element Analysis in order to predict the mechanical behavior and the vascular trauma. In this way, the stents were considered as tubular devices composed of multiple links under radial pressure loads, reflecting stress concentration effects. The analysis allowed to visualize how the geometry of stents is adjusted under several load conditions, in order to obtain the response of "solid-solid" interaction between the stent and the arterial wall. Thus, an analysis was performed in order to calculate stress, and a conceptual model that explains its mechanical impact on the stent-vessel interaction, was raised, to infer on the functionality from the design of the devices. The proposed conceptual model allows to determine the relationship between the conditions of mechanical interaction of the stents, and warns about the effects in what would be the operation of the device on the vascular environment. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

The extracranial venous system in the heads of beaked whales, with implications on diving physiology and pathogenesis.

PubMed

Costidis, Alexander M; Rommel, Sentiel A

2016-01-01

Beaked whales are a poorly known but diverse group of whales that have received considerable attention due to strandings that have been temporally and spatially associated with naval sonar deployment. Postmortem studies on stranded carcasses have revealed lesions consistent with decompression sickness, including intravascular gas and fat emboli. These findings have been supported by analyses of intravascular gas emboli showing composition dominated by nitrogen gas. To increase our understanding of the pathophysiology of nitrogen bubble formation and intravascular embolization, we examined the gross and microscopic anatomy of the venous system in the head of beaked whales. Since the potential sources of intravascular fat and gas emboli were of greatest interest, focus was placed on the acoustic fat bodies and pneumatic accessory sinus system. Herein, we describe intimate arteriovenous associations with specialized adipose depots and air sinuses in beaked whales. These vascular structures comprise an extensive network of thin-walled vessels with a large surface area, which is likely to facilitate exchange of nitrogen gas and may, therefore, form anatomic regions that may be important in physiological management of diving gases. These structures may also be vulnerable to pathologic introduction of emboli into the vascular system. Expansive, thin-walled venous lakes are found within the pterygoid region, which suggest the potential for nitrogen exchange as well as for compensation of middle-ear pressures during descent on a dive. These findings warrant further research into the structure and function of this morphology as it relates to normal and pathologic physiology. © 2015 Wiley Periodicals, Inc.

Hypergravity Effects on Dendritic Cells and Vascular Wall Interactions

NASA Astrophysics Data System (ADS)

Bellik, L.; Parenti, A.; Ledda, F.; Basile, V.; Romano, G.; Fusi, F.; Monici, M.

2009-01-01

Dendritic cells (DCs), the most potent antigen-presenting cells inducing specific immune responses, are involved in the pathogenesis of atherosclerosis. In this inflammatory disease, DCs increase in number, being particularly abundant in the shoulder regions of plaques. Since the exposure to altered gravitational conditions results in a significant impairment of the immune function, the aim of this study was to investigate the effects of hypergravity on both the function of DCs and their interactions with the vascular wall cells. Monocytes from peripheral blood mononuclear cells of healthy volunteers were sorted by CD14+ magnetic beads selection, cultured for 6 days in medium supplemented with GM-CSF and IL-4, followed by a further maturation stimulus. DC phenotype, assessed by flow cytometry, showed a high expression of the specific DC markers CD80, CD86, HLA-DR and CD83. The DCs obtained were then exposed to hypergravitational stimuli and their phenotype, cytoskeleton, ability to activate lymphocytes and interaction with vascular wall cells were investigated. The findings showed that the exposure to hypergravity conditions resulted in a significant impairment of DC cytoskeletal organization, without affecting the expression of DC markers. Moreover, an increase in DC adhesion to human vascular smooth muscle cells and in their ability to activate lymphocytes was observed.

Infrared nanospectroscopy reveals the chemical nature of pit membranes in water-conducting cells of the plant xylem.

PubMed

Pereira, Luciano; Flores-Borges, Denisele; Bittencourt, Paulo; Mayer, Juliana; Kiyota, Eduardo; Araújo, Pedro; Jansen, Steven; Freitas, Raul; Oliveira, Rafael; Mazzafera, Paulo

2018-06-05

In the xylem of angiosperm plants, microscopic pits through the secondary cell walls connect the water-conducting vessels. Cellulosic meshes originated from primary walls and middle lamella between adjacent vessels, called pit membrane, separates one conduit from another. The intricate structure of the nano-sized pores in pit membranes enables the passage of water under negative pressure without hydraulic failure due to obstruction by gas bubbles (i.e., embolism) under normal conditions or mild drought stress. Since the chemical composition of pit membranes affects embolism formation and bubble behavior, we directly measured pit membrane composition in Populus nigra wood. Here, we characterized the chemical composition of cell wall structures by synchrotron infrared nanospectroscopy and atomic force microscopy-infrared nanospectroscopy with high spatial resolution. Characteristic peaks of cellulose, phenolic compounds, and proteins were found in the intervessel pit membrane of P. nigra wood. In addition, vessel to parenchyma pit membranes and developing cell walls of the vascular cambium showed clear signals of cellulose, proteins, and pectin. We did not find a distinct peak of lignin and other compounds in these structures. Our investigation of the complex chemical composition of intervessel pit membranes furthers our understanding of the flow of water and bubbles between neighboring conduits. The advances presented here pave the way for further label-free studies related to the nano-chemistry of plant cell components. {copyright, serif} 2018 American Society of Plant Biologists. All rights reserved.

Differential metabolism of pectic galactan in tomato and strawberry fruit: detection of the LM26 branched galactan epitope in ripe strawberry fruit.

PubMed

Posé, Sara; Marcus, Susan E; Paul Knox, J

2018-04-24

Antibody-based approaches have been used to study cell wall architecture and modifications during the ripening process of two important fleshy fruit crops: tomato and strawberry. Cell wall polymers in both unripe and ripe fruits have been sequentially solubilized and fractions analysed with sets of monoclonal antibodies focusing on the pectic polysaccharides. We demonstrate the specific detection of the LM26 branched galactan epitope, associated with rhamnogalacturonan-I, in cell walls of ripe strawberry fruit. Analytical approaches confirm that the LM26 epitope is linked to sets of rhamnogalacturonan-I and homogalacturonan molecules. The cellulase-degradation of cellulose-rich residues that releases cell wall polymers intimately linked with cellulose microfibrils has been used to explore aspects of branched galactan occurrence and galactan metabolism. In situ analyses of ripe strawberry fruits indicate that the LM26 epitope is present in all primary cell walls and also particularly abundant in vascular tissues. The significance of the occurrence of branched galactan structures in the side chains of rhamnogalacturonan-I pectins in the context of ripening strawberry fruit is discussed. This article is protected by copyright. All rights reserved.

Modulation of Endothelial Glycocalyx Structure under Inflammatory Conditions

PubMed Central

Kolářová, Hana; Ambrůzová, Barbora; Švihálková Šindlerová, Lenka; Klinke, Anna; Kubala, Lukáš

2014-01-01

The glycocalyx of the endothelium is an intravascular compartment that creates a barrier between circulating blood and the vessel wall. The glycocalyx is suggested to play an important role in numerous physiological processes including the regulation of vascular permeability, the prevention of the margination of blood cells to the vessel wall, and the transmission of shear stress. Various theoretical models and experimental approaches provide data about changes to the structure and functions of the glycocalyx under various types of inflammatory conditions. These alterations are suggested to promote inflammatory processes in vessels and contribute to the pathogenesis of number of diseases. In this review we summarize current knowledge about the modulation of the glycocalyx under inflammatory conditions and the consequences for the course of inflammation in vessels. The structure and functions of endothelial glycocalyx are briefly discussed in the context of methodological approaches regarding the determination of endothelial glycocalyx and the uncertainty and challenges involved in glycocalyx structure determination. In addition, the modulation of glycocalyx structure under inflammatory conditions and the possible consequences for pathogenesis of selected diseases and medical conditions (in particular, diabetes, atherosclerosis, ischemia/reperfusion, and sepsis) are summarized. Finally, therapeutic strategies to ameliorate glycocalyx dysfunction suggested by various authors are discussed. PMID:24803742

D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury

PubMed Central

Miyahara, Takuya; Runge, Sara; Chatterjee, Anuran; Chen, Mian; Mottola, Giorgio; Fitzgerald, Jonathan M.; Serhan, Charles N.; Conte, Michael S.

2013-01-01

Recent evidence suggests that specialized lipid mediators derived from polyunsaturated fatty acids control resolution of inflammation, but little is known about resolution pathways in vascular injury. We sought to determine the actions of D-series resolvin (RvD) on vascular smooth muscle cell (VSMC) phenotype and vascular injury. Human VSMCs were treated with RvD1 and RvD2, and phenotype was assessed by proliferation, migration, monocyte adhesion, superoxide production, and gene expression assays. A rabbit model of arterial angioplasty with local delivery of RvD2 (10 nM vs. vehicle control) was employed to examine effects on vascular injury in vivo. Local generation of proresolving lipid mediators (LC-MS/MS) and expression of RvD receptors in the vessel wall were assessed. RvD1 and RvD2 produced dose-dependent inhibition of VSMC proliferation, migration, monocyte adhesion, superoxide production, and proinflammatory gene expression (IC50≈0.1–1 nM). In balloon-injured rabbit arteries, cell proliferation (51%) and leukocyte recruitment (41%) were reduced at 3 d, and neointimal hyperplasia was attenuated (29%) at 28 d by RvD2. We demonstrate endogenous biosynthesis of proresolving lipid mediators and expression of receptors for RvD1 in the artery wall. RvDs broadly reduce VSMC responses and modulate vascular injury, suggesting that local activation of resolution mechanisms expedites vascular homeostasis.—Miyahara, T., Runge, S., Chatterjee, A., Chen, M., Mottola, G., Fitzgerald, J. M., Serhan, C. N., Conte, M. S. D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury. PMID:23407709

Structural modifications in the arterial wall during physiological aging and as a result of diabetes mellitus in a mouse model: are the changes comparable?

PubMed

Prévost, G; Bulckaen, H; Gaxatte, C; Boulanger, E; Béraud, G; Creusy, C; Puisieux, F; Fontaine, P

2011-04-01

Vascular accelerated aging represents the major cause of morbidity and mortality in subjects with diabetes mellitus. In the present study, our aim was to compare premature functional and morphological changes in the arterial wall resulting from streptozotocin (STZ)-induced diabetes mellitus in mice over a short-term period with those that develop during physiological aging. The effect of aminoguanidine (AG) on the prevention of these alterations in the diabetic group was also analyzed. The vascular relaxation response to acetylcholine (ACh) in the mouse was tested in isolated segments of phenylephrine (Phe)-precontracted aorta at 2, 4 and 8 weeks (wk) of STZ-induced diabetes and compare to 12- and 84-wk-old mice. Aortic structural changes were investigated, and receptor for AGE (RAGE) aortic expression was quantified by western blot. Compared to the 12-wk control group (76 ± 5%), significant endothelium-dependant relaxation (EDR) impairment was found in the group of 12-wk-old mice, which underwent a 4-wk diabetes-inducing STZ treatment (12wk-4WD) (52 ± 4%; P < 0.01) and was yet more apparent in the group of 16-wk-old mice, which underwent an 8-wk diabetes-inducing STZ treatment (16wk-8WD) (34 ± 4%; P < 0.001). The alteration in EDR was relatively comparable between the diabetic 12wk-4WD group and the 84-wk-old group (52.7 ± 4 vs. 48 ± 4%). Intima/media aortic thickening and aortic structural changes were significantly increased in the diabetic 12wk-4WD group and were even more apparent in the 84-wk group compared to the 12-wk controls. AG treatment in the 12wk-4WD+AG diabetic group significantly improved EDR, decreased RAGE expression and showed an aging preventive effect on the structural changes of the arterial wall. Our study compared EDR linked to physiological aging with that observed in the case of STZ-induced diabetes over a short-term period, and demonstrated the beneficial effect of AG. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Histologic change of arteriovenous malformations of the face and scalp after free flap transfer.

PubMed

Tark, K C; Chung, S

2000-07-01

In three patients with long-standing vascular malformations of the face and scalp, radial forearm free flaps were transferred after a near-total excision of the lesion. All patients had typical high-flow malformations with thrill and bruit. The onset and progression of the malformations were analyzed through clinical and histologic studies. After free flap transfer, the vascular malformations were followed up grossly and histologically for between 4 and 9 years. There was no recurrence of arteriovenous malformation after free flap transfer. The portion of the residual lesion adjacent to the transferred free flap disappeared, and the remaining discoloration also vanished grossly. Histologic comparison of immediate postoperative and 4-month postoperative specimens from the margin and residual lesion using Victoria blue staining showed that the typical preoperative findings for arteriovenous malformation-an intermingling of thick-walled vessels with abundant elastic fibers and thin-walled vessels without elastic fibers-had undergone change, resulting in the disappearance of the thick-walled vessels and leaving only homogeneous, thin-walled vasculature. The highly vascularized free flap, which does not contain abnormal fistulas, impacted the histologic change of the arteriovenous malformation by blocking the vicious cycle of ischemia and anatomic replacement of disfigured skin and subcutaneous tissues.

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor.

PubMed

Ball, Owen; Nguyen, Bao-Ngoc B; Placone, Jesse K; Fisher, John P

2016-12-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state.

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor

PubMed Central

Ball, Owen; Nguyen, Bao-Ngoc B.; Placone, Jesse K.; Fisher, John P.

2016-01-01

There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state. PMID:27272210

Vascular adaptations for heat conservation in the tail of Florida manatees (Trichechus manatus latirostris)

PubMed Central

Rommel, Sentiel A; Caplan, Heather

2003-01-01

Although Florida manatees (Trichechus manatus latirostris) have relatively low basal metabolic rates for aquatic mammals of their size, they maintain normal mammalian core temperatures. We describe vascular structures in the manatee tail that permit countercurrent heat exchange (CCHE) to conserve thermal energy. Approximately 1000 arteries juxtaposed to 2000 veins are found at the cranial end of the caudal vascular bundle (CVB); these numbers decrease caudally, but the 1 : 2 ratio of arteries to veins persists. Arterial walls are relatively thin when compared to those previously described in vascular countercurrent heat exchangers in cetaceans. It is assumed that CCHE in the CVB helps manatees to maintain core temperatures. Activity in warm water, however, mandates a mechanism that prevents elevated core temperatures. The tail could transfer heat to the environment if arterial blood delivered to the skin were warmer than the surrounding water; unfortunately, CCHE prevents this heat transfer. We describe deep caudal veins that provide a collateral venous return from the tail. This return, which is physically outside the CVB, reduces the venous volume within the bundle and allows arterial expansion and increased arterial supply to the skin, and thus helps prevent elevated core temperatures. PMID:12739612

Vascular adaptations for heat conservation in the tail of Florida manatees (Trichechus manatus latirostris).

PubMed

Rommel, Sentiel A; Caplan, Heather

2003-04-01

Although Florida manatees (Trichechus manatus latirostris) have relatively low basal metabolic rates for aquatic mammals of their size, they maintain normal mammalian core temperatures. We describe vascular structures in the manatee tail that permit countercurrent heat exchange (CCHE) to conserve thermal energy. Approximately 1000 arteries juxtaposed to 2000 veins are found at the cranial end of the caudal vascular bundle (CVB); these numbers decrease caudally, but the 1:2 ratio of arteries to veins persists. Arterial walls are relatively thin when compared to those previously described in vascular countercurrent heat exchangers in cetaceans. It is assumed that CCHE in the CVB helps manatees to maintain core temperatures. Activity in warm water, however, mandates a mechanism that prevents elevated core temperatures. The tail could transfer heat to the environment if arterial blood delivered to the skin were warmer than the surrounding water; unfortunately, CCHE prevents this heat transfer. We describe deep caudal veins that provide a collateral venous return from the tail. This return, which is physically outside the CVB, reduces the venous volume within the bundle and allows arterial expansion and increased arterial supply to the skin, and thus helps prevent elevated core temperatures.

Stem/Progenitor Cell–Mediated De Novo Regeneration of Dental Pulp with Newly Deposited Continuous Layer of Dentin in an In Vivo Model

PubMed Central

Yamaza, Takayoshi; Shea, Lonnie D.; Djouad, Farida; Kuhn, Nastaran Z.; Tuan, Rocky S.; Shi, Songtao

2010-01-01

The ultimate goal of this study is to regenerate lost dental pulp and dentin via stem/progenitor cell–based approaches and tissue engineering technologies. In this study, we tested the possibility of regenerating vascularized human dental pulp in emptied root canal space and producing new dentin on existing dentinal walls using a stem/progenitor cell–mediated approach with a human root fragment and an immunocompromised mouse model. Stem/progenitor cells from apical papilla and dental pulp stem cells were isolated, characterized, seeded onto synthetic scaffolds consisting of poly-D,L-lactide/glycolide, inserted into the tooth fragments, and transplanted into mice. Our results showed that the root canal space was filled entirely by a pulp-like tissue with well-established vascularity. In addition, a continuous layer of dentin-like tissue was deposited onto the canal dentinal wall. This dentin-like structure appeared to be produced by a layer of newly formed odontoblast-like cells expressing dentin sialophosphoprotein, bone sialoprotein, alkaline phosphatase, and CD105. The cells in regenerated pulp-like tissue reacted positively to anti-human mitochondria antibodies, indicating their human origin. This study provides the first evidence showing that pulp-like tissue can be regenerated de novo in emptied root canal space by stem cells from apical papilla and dental pulp stem cells that give rise to odontoblast-like cells producing dentin-like tissue on existing dentinal walls. PMID:19737072

The wall traction induced by flowing red blood cells in model microvessels and its potential mechanotransduction

NASA Astrophysics Data System (ADS)

Freund, Jonathan; Vermot, Julien

2013-11-01

There is evidence in early embryonic development, even well before advective oxygen transport is important, that the presence of red bloods cells per se trigger essential steps of normal vascular development. For example, showed that sequestration of blood cells early in the development of a mouse, such that the hematocrit is reduced, suppresses normal vascular network development. Vascular development also provides a model for remodeling and angiogenesis. We consider the transient stresses associated with blood cells flowing in model microvessels of comparable diameter to those at early stages of development (6 μm to 12 μm). A detailed simulation tool is used to show that passing blood cells present a significant fluctuating traction signature on the vessel wall, well above the mean stresses. This is particularly pronounced for slow flows (<= 50 μm/s) or small diameters (<= 7 μm), for which root-mean-square wall traction fluctuations can exceed their mean. These events potentially present mechanotranduction triggers that direct development or remodeling. Attenuation of such fluctuating tractions by a viscoelastic endothelial glycocalyx layer is also considered. NSF supported.

Proteomic Profiling of Tissue-Engineered Blood Vessel Walls Constructed by Adipose-Derived Stem Cells

PubMed Central

Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang

2013-01-01

Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels. PMID:22963350

Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.

PubMed

Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang; Cui, Lei

2013-02-01

Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels.

Lung capillary injury and repair in left heart disease: a new target for therapy?

PubMed

Azarbar, Sayena; Dupuis, Jocelyn

2014-07-01

The lungs are the primary organs affected in LHD (left heart disease). Increased left atrial pressure leads to pulmonary alveolar-capillary stress failure, resulting in cycles of alveolar wall injury and repair. The reparative process causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. Although the resultant reduction in vascular permeability is initially protective against pulmonary oedema, the process becomes maladaptive causing a restrictive lung syndrome with impaired gas exchange. This pathological process may also contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have specifically evaluated lung structural remodelling and the effect of related therapies in LHD. Currently approved treatment for chronic HF (heart failure) may have direct beneficial effects on lung structural remodelling. In the future, novel therapies specifically targeting the remodelling processes may potentially be utilized. In the present review, we summarize data supporting the clinical importance and pathophysiological mechanisms of lung structural remodelling in LHD and propose that this pathophysiological process should be explored further in pre-clinical studies and future therapeutic trials.

Matrix Metalloproteinases as Regulators of Vein Structure and Function: Implications in Chronic Venous Disease.

PubMed

MacColl, Elisabeth; Khalil, Raouf A

2015-12-01

Lower-extremity veins have efficient wall structure and function and competent valves that permit upward movement of deoxygenated blood toward the heart against hydrostatic venous pressure. Matrix metalloproteinases (MMPs) play an important role in maintaining vein wall structure and function. MMPs are zinc-binding endopeptidases secreted as inactive pro-MMPs by fibroblasts, vascular smooth muscle (VSM), and leukocytes. Pro-MMPs are activated by various activators including other MMPs and proteinases. MMPs cause degradation of extracellular matrix (ECM) proteins such as collagen and elastin, and could have additional effects on the endothelium, as well as VSM cell migration, proliferation, Ca(2+) signaling, and contraction. Increased lower-extremity hydrostatic venous pressure is thought to induce hypoxia-inducible factors and other MMP inducers/activators such as extracellular matrix metalloproteinase inducer, prostanoids, chymase, and hormones, leading to increased MMP expression/activity, ECM degradation, VSM relaxation, and venous dilation. Leukocyte infiltration and inflammation of the vein wall cause further increases in MMPs, vein wall dilation, valve degradation, and different clinical stages of chronic venous disease (CVD), including varicose veins (VVs). VVs are characterized by ECM imbalance, incompetent valves, venous reflux, wall dilation, and tortuosity. VVs often show increased MMP levels, but may show no change or decreased levels, depending on the VV region (atrophic regions with little ECM versus hypertrophic regions with abundant ECM) and MMP form (inactive pro-MMP versus active MMP). Management of VVs includes compression stockings, venotonics, and surgical obliteration or removal. Because these approaches do not treat the causes of VVs, alternative methods are being developed. In addition to endogenous tissue inhibitors of MMPs, synthetic MMP inhibitors have been developed, and their effects in the treatment of VVs need to be examined. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Hypertrophy of the vasa vasorum: vascular response to the hungry brain.

PubMed

Cho, Hyun-Ji; Roh, Hong Gee; Chun, Young Il; Moon, Chang Taek; Chung, Hyun Woo; Kim, Hahn Young

2012-05-01

The vasa vasorum is a network of microvessels that supplies nutrients to the vessel wall itself. In pathologic conditions, the vasa vasorum can develop as potential collateral channels. Previous research documents revascularization through hypertrophy of the vasa vasorum after occlusion of the carotid artery. However, the relationship between the cerebral vascular demands and the hypertrophy of the vasa vasorum has not been well delineated by functional studies. A 66-year-old man presented with left hemiparesis, dysarthria, and hemineglect. Magnetic resonance imaging revealed an acute infarction in the vascular territory of the right middle cerebral artery. Transfemoral cerebral angiography revealed occlusion of the right proximal internal carotid artery (ICA). Single-photon emission computed tomography study showed decreased vascular reserve in the right cerebral hemisphere. Right superficial temporal artery-middle cerebral artery bypass surgery was performed in an attempt to improve hemispheric perfusion. Follow-up angiography 1 year later showed revascularization of the distal ICA by the hypertrophied vasa vasorum. Follow-up single-photon emission computed tomography study showed persistent decreased vascular reserve. In cases of ICA occlusion, a 1-year or less hungry period for the cerebral vascular demand may activate potential collateral channels of the vasa vasorum. In addition to the metabolic demand of the occluded vessel wall itself, the vascular demands of the hypoperfused brain may be a trigger factor that leads to hypertrophy of the vasa vasorum as collateral channels.

The current role of vascular stents.

PubMed

Busquet, J

1993-09-01

The limitations of percutaneous balloon angioplasty have favoured the development and the use of vascular endoprostheses or stents. These thin-walled metal devices maintain after expansion, an optimal and constant diameter for the vascular lumen. Restenosis, dissection, abrupt closure, residual stenosis or re-opened total occlusion represent appropriate indications for stenting. A large experience with non-coronary application of stents is currently available in iliac, femoro-popliteal and renal arteries, aorta, large veins.

The plant cell wall in the feeding sites of cyst nematodes.

PubMed

Bohlmann, Holger; Sobczak, Miroslaw

2014-01-01

Plant parasitic cyst nematodes (genera Heterodera and Globodera) are serious pests for many crops. They enter the host roots as migratory second stage juveniles (J2) and migrate intracellularly toward the vascular cylinder using their stylet and a set of cell wall degrading enzymes produced in the pharyngeal glands. They select an initial syncytial cell (ISC) within the vascular cylinder or inner cortex layers to induce the formation of a multicellular feeding site called a syncytium, which is the only source of nutrients for the parasite during its entire life. A syncytium can consist of more than hundred cells whose protoplasts are fused together through local cell wall dissolutions. While the nematode produces a cocktail of cell wall degrading and modifying enzymes during migration through the root, the cell wall degradations occurring during syncytium development are due to the plants own cell wall modifying and degrading proteins. The outer syncytial cell wall thickens to withstand the increasing osmotic pressure inside the syncytium. Furthermore, pronounced cell wall ingrowths can be formed on the outer syncytial wall at the interface with xylem vessels. They increase the surface of the symplast-apoplast interface, thus enhancing nutrient uptake into the syncytium. Processes of cell wall degradation, synthesis and modification in the syncytium are facilitated by a variety of plant proteins and enzymes including expansins, glucanases, pectate lyases and cellulose synthases, which are produced inside the syncytium or in cells surrounding the syncytium.

Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.

PubMed

Kovalyov, Oleksiy O; Kostyuk, Oleksandr G; Tkachuk, Tetyana V

To provide long-term vascular access in clinical oncology peripheral forearm veins (up to 95% of patients in Ukraine), central venous access and "complete implanted vascular systems" are used most often. Many oncology patients have contraindications to catheterization of superior vena cava. Besides, exploitation of central veins is associated with potential technical and infectious complications. The aim - to study short-term and long-term results of arteriovenous fistula exploitation as vascular access for continuous anticancer therapy. Peripheral venous bed status in 41 oncology patients taking long-term chemotherapy treatment is analyzed in the article. Doppler sonography, morphologic and immune histochemical analyses were used in the study. Doppler sonography found qualitative and quantitative changes in forearm veins at different time periods after initiation of chemotherapy in the majority of patients. The major morphologic manifestations of venous wall damage were chemical phlebitis, local or extended hardening of venous wall, venous thrombosis and extravasations with necrosis and subsequent paravasal tissue sclerosis. Alternative vascular access created in 12 patients completely met the adequacy criteria (safety, multiple use, longevity, realization of the designed therapy program). The conclusion was made about inapplicability of forearm veins for long-term administration of cytostatic agents. If it is impossible to use central veins, arteriovenous fistula can become an alternative vascular access.

Effect of gravitational acceleration, hypokinesia and hypodynamia on the structure of the intestinal vascular bed

NASA Technical Reports Server (NTRS)

Nikitin, M. V.

1980-01-01

A series of experiments comparing single and combined effects of hypokinesia and gravitational acceleration on morphology of intestinal blood vessels are discussed. Results indicate that hypokinesia has a whole body nonspecific effect reflected even in an organ whose activity shows little or no change due to hypokinesia. In early hypokinetic stages blood redistribution caused anorexia, intestinal atonia, and secretory disruption. Destructive changes from further exposure include aneurisms, varicoses, extravascular movement of blood elements, and vascular wall muscle fiber degeneration. The effect of acceleration is greatest in the ventrodorsal direction. Changes due to acceleration then hypokinesia are like those due to hypokinesia alone; changes due to acceleration before and after hypokinesia are like those due to acceleration. Adaptation raises acceleration tolerance but the effects do not survive four-week hypokinesia.

Optical coherence domain reflectometry guidewire

DOEpatents

Colston, Billy W.; Everett, Matthew; Da Silva, Luiz B.; Matthews, Dennis

2001-01-01

A guidewire with optical sensing capabilities is based on a multiplexed optical coherence domain reflectometer (OCDR), which allows it to sense location, thickness, and structure of the arterial walls or other intra-cavity regions as it travels through the body during minimally invasive medical procedures. This information will be used both to direct the guidewire through the body by detecting vascular junctions and to evaluate the nearby tissue. The guidewire contains multiple optical fibers which couple light from the proximal to distal end. Light from the fibers at the distal end of the guidewire is directed onto interior cavity walls via small diameter optics such as gradient index lenses and mirrored corner cubes. Both forward viewing and side viewing fibers can be included. The light reflected or scattered from the cavity walls is then collected by the fibers, which are multiplexed at the proximal end to the sample arm of an optical low coherence reflectometer. The guidewire can also be used in nonmedical applications.

A new simplified methodology for studying the coupled fluid-structure interaction in a weakened basilar artery.

PubMed

Montanino, A; Fortunato, A; Angelillo, M

2016-07-01

In this paper, we study the fluid-structure interaction in a weakened basilar artery. The aim is to study how the wall shear stress changes in space and time because of the weakening, because spatial and temporal changes are thought to be possible causes of aneurysm and vascular deseases. The arterial wall, in its natural configuration, is modeled as a hyperelastic cylinder, inhomogeneous along its axis, in order to simulate the axis-symmetric weakening. The fluid is studied exploiting a recent approach for quasi-one-dimensional flows in slowly varying ducts, which allows to write the averaged equations of mass and energy balance on the basis of the velocity profile in a straight duct. The unknowns are the wall pressure, the average velocity, and the wall radial displacement. The problem is solved in two parts: first, the stationary non-linear coupled problem is solved, and an intermediate configuration is obtained. Then, we study the variation of the basic unknowns about the intermediate configuration, considering time dependence over the cardiac cycles. The results suggest that, with a 10% reduction of the main elastic modulus, the shear stress in the weakened zone changes its sign and doubles the maximum stress value detected in the healthy zone. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Responses of adventitial CD34+ vascular wall-resident stem/progenitor cells and medial smooth muscle cells to carotid injury in rats.

PubMed

Shen, Yan; Wu, Yan; Zheng, Yong; Ao, Feng; Kang, Kai; Wan, Yu; Song, Jian

2016-12-01

Cell culture and carotid injury studies with SD rats were performed to investigate the roles of CD34 + vascular wall-resident stem/progenitor cells (VRS/Pcs) and vascular smooth muscle cells (SMCs) in neointimal formation. In vitro, the media-isolated SM MHC + SMCs occupied 93.92±8.62% of total BrdU + cells, whereas the CD34 + cells, only 2.61±0.82%, indicating that the cell expansion in SMC culture was attributed to SM MHC + SMCs. The adventitia-isolated CD34 + VRS/Pcs responded to PDGF-BB by differentiating into SMC-like cells which expressed SM22α (an early stage SMC marker), but seldom SM MHC (a late stage SMC marker). In carotid injury model, the CD34 + VRS/Pcs differentiated SMC-like cells migrated in very few numbers into only the outer layer of the media, and this was further confirmed by a cell tracking analysis. While the neointimal cells were consistently SM MHC + and CD34 - SMCs during whole course of the post-injury remodeling. Thus it is speculated that the adventitial CD34 + VRS/Pcs, at least in rat model, do not directly participate in neointimal formation, but function to maintain homeostasis of the media during injury-induced vascular wall remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic Potential of Modulating microRNAs in Atherosclerotic Vascular Disease

PubMed Central

Araldi, Elisa; Chamorro-Jorganes, Aranzazu; van Solingen, Coen; Fernández-Hernando, Carlos; Suárez, Yajaira

2013-01-01

Atherosclerosis (also known as arteriosclerotic vascular disease) is a chronic inflammatory disease of the arterial wall, characterized by the formation of lipid-laden lesions. The activation of endothelial cells at atherosclerotic lesion–prone sites in the arterial tree results in the up-regulation of cell adhesion molecules and chemokines, which mediate the recruitment of circulating monocytes. Accumulation of monocytes and monocyte-derived phagocytes in the wall of large arteries leads to chronic inflammation and the development and progression of atherosclerosis. The lesion experiences the following steps: foam cell formation, fatty streak accumulation, migration and proliferation of vascular smooth muscle cells, and fibrous cap formation. Finally, the rupture of the unstable fibrous cap causes thrombosis in complications of advanced lesions that leads to unstable coronary syndromes, myocardial infarction and stroke. MicroRNAs have recently emerged as a novel class of gene regulators at the post-transcriptional level. Several functions of vascular cells, such as cell differentiation, contraction, migration, proliferation and inflammation that are involved in angiogenesis, neointimal formation and lipid metabolism underlying various vascular diseases, have been found to be regulated by microRNAs and are described in the present review as well as their potential therapeutic application. PMID:23713860

Simulation of blood flow in a small-diameter vascular graft model with a swirl (spiral) flow guider.

PubMed

Zhang, ZhiGuo; Fan, YuBo; Deng, XiaoYan; Wang, GuiXue; Zhang, He; Guidoin, Robert

2008-10-01

Small-diameter vascular grafts are in large demand for coronary and peripheral bypass procedures, but present products still fail in long-term clinical application. In the present communication, a new type of small-diameter graft with a swirl flow guider was proposed to improve graft patency rate. Flow pattern in the graft was simulated numerically and compared with that in a conventional graft. The numerical results revealed that the swirl flow guider could indeed make the blood flow rotate in the new graft. The swirling flow distal to the flow guider significantly altered the flow pattern in the new graft and the velocity profiles were re-distributed. Due to the swirling flow, the blood velocity near the vessel wall and wall shear rate were greatly enhanced. We believe that the increased blood velocity near the wall and the wall shear rate can impede the occurrence of acute thrombus formation and intimal hyperplasia, hence can improve the graft patency rate for long-term clinical use.

Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, Yaoqian; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163; Balazs, Louisa

2011-05-13

Highlights: {yields} Deletion of Dicer in vascular smooth muscle cells(VSMCs) leads to embryonic mortality. {yields} Loss of Dicer in VSMCs leads to developmental delay. {yields} Loss of Dicer in VSMCs leads to hemorrhage in various organs including brain, skin and liver. {yields} Loss of Dicer in VSMCs leads to vascular wall remodeling. {yields} Loss of Dicer in VSMCs dysregulates the expression of miRNA and VSMC marker genes. -- Abstract: Dicer is a RNAase III enzyme that cleaves double stranded RNA and generates small interfering RNA (siRNA) and microRNA (miRNA). The goal of this study is to examine the role ofmore » Dicer and miRNAs in vascular smooth muscle cells (VSMCs). We deleted Dicer in VSMCs of mice, which caused a developmental delay that manifested as early as embryonic day E12.5, leading to embryonic death between E14.5 and E15.5 due to extensive hemorrhage in the liver, brain, and skin. Dicer KO embryos showed dilated blood vessels and a disarray of vascular architecture between E14.5 and E15.5. VSMC proliferation was significantly inhibited in Dicer KOs. The expression of VSMC marker genes were significantly downregulated in Dicer cKO embryos. The vascular structure of the yolk sac and embryo in Dicer KOs was lost to an extent that no blood vessels could be identified after E15.5. Expression of most miRNAs examined was compromised in VSMCs of Dicer KO. Our results indicate that Dicer is required for vascular development and regulates vascular remodeling by modulating VSMC proliferation and differentiation.« less

Cardiovascular causes of airway compression.

PubMed

Kussman, Barry D; Geva, Tal; McGowan, Francis X

2004-01-01

Compression of the paediatric airway is a relatively common and often unrecognized complication of congenital cardiac and aortic arch anomalies. Airway obstruction may be the result of an anomalous relationship between the tracheobronchial tree and vascular structures (producing a vascular ring) or the result of extrinsic compression caused by dilated pulmonary arteries, left atrial enlargement, massive cardiomegaly, or intraluminal bronchial obstruction. A high index of suspicion of mechanical airway compression should be maintained in infants and children with recurrent respiratory difficulties, stridor, wheezing, dysphagia, or apnoea unexplained by other causes. Prompt diagnosis is required to avoid death and minimize airway damage. In addition to plain chest radiography and echocardiography, diagnostic investigations may consist of barium oesophagography, magnetic resonance imaging (MRI), computed tomography, cardiac catheterization and bronchoscopy. The most important recent advance is MRI, which can produce high quality three-dimensional reconstruction of all anatomic elements allowing for precise anatomic delineation and improved surgical planning. Anaesthetic technique will depend on the type of vascular ring and the presence of any congenital heart disease or intrinsic lesions of the tracheobronchial tree. Vascular rings may be repaired through a conventional posterolateral thoracotomy, or utilizing video-assisted thoracoscopic surgery (VATS) or robotic endoscopic surgery. Persistent airway obstruction following surgical repair may be due to residual compression, secondary airway wall instability (malacia), or intrinsic lesions of the airway. Simultaneous repair of cardiac defects and vascular tracheobronchial compression carries a higher risk of morbidity and mortality.

Totally implanted ports: the trapezius approach in practice.

PubMed

Hill, Steve

Implanted ports (IPs) are an essential device for many patients who require long-term vascular access. IPs offer some advantages over other central venous access devices, such as lifestyle, body image benefits and lower infection rates. A typical implantation site for a port is the anterior chest wall. For some patients with breast cancer who have metastatic chest wall disease this site may lead to problems with the function of the device if disease spreads to the port site. One option for this patient group is to place the implanted port over the trapezius muscle. This article discusses six patients, all of whom had metastatic breast cancer with some degree of subcutaneous disease on the anterior chest wall. Three patients had received trapezius port placements and three had anterior chest wall placements. A retrospective review of the patients' medical records was undertaken from the time of insertion until removal or until the patient died. The anterior chest wall group of patients had their devices in for an average of 368 days vs 214 in the trapezius group. The total complications were higher in the anterior chest wall group (7 vs 2 in the trapezius group). Disease spread to two of the devices in the anterior chest wall group meaning the devices could no longer be used. The trapezius approach appears to be a safe and a reliable form of vascular access and may offer fewer complications than the traditional method of anterior chest wall placement when standard anterior chest wall approach is not suitable.

Flow effects of blood constitutive equations in 3D models of vascular anomalies

NASA Astrophysics Data System (ADS)

Neofytou, Panagiotis; Tsangaris, Sokrates

2006-06-01

The effects of different blood rheological models are investigated numerically utilizing two three- dimensional (3D) models of vascular anomalies, namely a stenosis and an abdominal aortic aneurysm model. The employed CFD code incorporates the SIMPLE scheme in conjunction with the finite-volume method with collocated arrangement of variables. The approximation of the convection terms is carried out using the QUICK differencing scheme, whereas the code enables also multi-block computations, which are useful in order to cope with the two-block grid structure of the current computational domain. Three non-Newtonian models are employed, namely the Casson, Power-Law and Quemada models, which have been introduced in the past for modelling the rheological behaviour of blood and cover both the viscous as well as the two-phase character of blood. In view of the haemodynamical mechanisms related to abnormalities in the vascular network and the role of the wall shear stress in initiating and further developing of arterial diseases, the present study focuses on the 3D flow field and in particular on the distribution as well as on both low and high values of the wall shear stress in the vicinity of the anomaly. Finally, a comparison is made between the effects of each rheological model on the aforementioned parameters. Results show marked differences between simulating blood as Newtonian and non-Newtonian fluid and furthermore the Power-Law model exhibits different behaviour in all cases compared to the other models whereas Quemada and Casson models exhibit similar behaviour in the case of the stenosis but different behaviour in the case of the aneurysm.

Effects of Inflorescence Stem Structure and Cell Wall Components on the Mechanical Strength of Inflorescence Stem in Herbaceous Peony

PubMed Central

Zhao, Daqiu; Han, Chenxia; Tao, Jun; Wang, Jing; Hao, Zhaojun; Geng, Qingping; Du, Bei

2012-01-01

Herbaceous peony (Paeonia lactiflora Pall.) is a traditional famous flower, but its poor inflorescence stem quality seriously constrains the development of the cut flower. Mechanical strength is an important characteristic of stems, which not only affects plant lodging, but also plays an important role in stem bend or break. In this paper, the mechanical strength, morphological indices and microstructure of P. lactiflora development inflorescence stems were measured and observed. The results showed that the mechanical strength of inflorescence stems gradually increased, and that the diameter of inflorescence stem was a direct indicator in estimating mechanical strength. Simultaneously, with the development of inflorescence stem, the number of vascular bundles increased, the vascular bundle was arranged more densely, the sclerenchyma cell wall thickened, and the proportion of vascular bundle and pith also increased. On this basis, cellulose and lignin contents were determined, PlCesA3, PlCesA6 and PlCCoAOMT were isolated and their expression patterns were examined including PlPAL. The results showed that cellulose was not strictly correlated with the mechanical strength of inflorescence stem, and lignin had a significant impact on it. In addition, PlCesA3 and PlCesA6 were not key members in cellulose synthesis of P. lactiflora and their functions were also different, but PlPAL and PlCCoAOMT regulated the lignin synthesis of P. lactiflora. These data indicated that PlPAL and PlCCoAOMT could be applied to improve the mechanical strength of P. lactiflora inflorescence stem in genetic engineering. PMID:22606025

Effects of inflorescence stem structure and cell wall components on the mechanical strength of inflorescence stem in herbaceous peony.

PubMed

Zhao, Daqiu; Han, Chenxia; Tao, Jun; Wang, Jing; Hao, Zhaojun; Geng, Qingping; Du, Bei

2012-01-01

Herbaceous peony (Paeonia lactiflora Pall.) is a traditional famous flower, but its poor inflorescence stem quality seriously constrains the development of the cut flower. Mechanical strength is an important characteristic of stems, which not only affects plant lodging, but also plays an important role in stem bend or break. In this paper, the mechanical strength, morphological indices and microstructure of P. lactiflora development inflorescence stems were measured and observed. The results showed that the mechanical strength of inflorescence stems gradually increased, and that the diameter of inflorescence stem was a direct indicator in estimating mechanical strength. Simultaneously, with the development of inflorescence stem, the number of vascular bundles increased, the vascular bundle was arranged more densely, the sclerenchyma cell wall thickened, and the proportion of vascular bundle and pith also increased. On this basis, cellulose and lignin contents were determined, PlCesA3, PlCesA6 and PlCCoAOMT were isolated and their expression patterns were examined including PlPAL. The results showed that cellulose was not strictly correlated with the mechanical strength of inflorescence stem, and lignin had a significant impact on it. In addition, PlCesA3 and PlCesA6 were not key members in cellulose synthesis of P. lactiflora and their functions were also different, but PlPAL and PlCCoAOMT regulated the lignin synthesis of P. lactiflora. These data indicated that PlPAL and PlCCoAOMT could be applied to improve the mechanical strength of P. lactiflora inflorescence stem in genetic engineering.

[Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor].

PubMed

Zhang, Minglei; Wang, Dapeng; Yin, Ruofeng

2015-10-06

To explorec Histocompatibility of nano-hydroxyapatite/poly-co-glycolic acid tissue engineering bone modified by mesenchymal stem cells with vascular endothelial frowth factor transinfected. Rat bone marrow mesenchymal stem cells (BMSCs) was separated, using BMSCs as target cells, and then vascular endothelial growth factor (VEGF) gene was transfected. Composite bone marrow mesenchymal stem cells and cells transfected with nano-hydroxyapatite (HA)/polylactic-co-glycolic acid (PLGA). The composition of cell and scaffold was observed. The blank plasmid transfection was 39.1%, 40.1% in VEGF group. The cell adhesion and growth was found on the scaffold pore wall after 5 days, and the number of adherent cells in the nano-HA/PLGA composite scaffold material basically had no significant difference in both. Although the nano-HA/PLGA scaffold material is still not fully meet the requirements of the matrix material for bone tissue engineering, but good biocompatibility, structure is its rich microporous satisfaction in material mechanics, toughening, enhanced obviously. Composition scaffold with BMSCs transfected by VEGF plasmid, the ability of angiogenesis is promoted.

Characterization of a novel glycine-rich protein from the cell wall of maize silk tissues.

PubMed

Tao, T Y; Ouellet, T; Dadej, K; Miller, S S; Johnson, D A; Singh, J

2006-08-01

The isolation, characterization and regulation of expression of a maize silk-specific gene is described. zmgrp5 (Zea mays glycine-rich protein 5) encodes a 187 amino acid glycine-rich protein that displays developmentally regulated silk-specific expression. Northern, Western, in situ mRNA hybridization and transient gene expression analyses indicate that zmgrp5 is expressed in silk hair and in cells of the vascular bundle and pollen tube transmitting tissue elements. The protein is secreted into the extracellular matrix and is localized in the cell wall fraction mainly through interactions mediated by covalent disulphide bridges. Taken together, these results suggest that the protein may play a role in maintaining silk structure during development. This is the first documented isolation of a stigma-specific gene from maize, an important agronomic member of the Poaceae family.

Effects of shoot inversion on stem structure in Pharbitis nil

NASA Technical Reports Server (NTRS)

Prasad, T. K.; Sack, F. D.; Cline, M. G.

1988-01-01

The effects of shoot inversion on stem structure over 72 hr were investigated in Pharbitis nil by analyzing cell number, cell length, and the cross sectional areas of cells, tissues, and regions. An increase in stem diameter can be attributed to an increase in both cell number and cross sectional area of pith (primarily) and vascular tissue (secondarily). Qualitative observations of cell wall thickness in the light microscope did not reveal any significant effects of shoot inversion on this parameter. The inhibition of shoot elongation was accompanied by a significant decrease in cell length in the pith. The results are generally consistent with an ethylene effect on cell dimensions, especially in the pith.

Influence of G-forces on venous and nervous systems

NASA Technical Reports Server (NTRS)

Dyskin, Y. A.; Prives-Bardina, R. A.; Tikhonova, L. P.

1975-01-01

Cats and rabbits were subjected to rotation in the centrifuge. Controls were maintained to determine the individual tolerance to g-forces. Thickening of the vascular wall was found to occur due to the g-forces' effect, as well as other vascular changes. Nervous changes included edema and chromatolysis of the nerve cells.

Wavelet analysis of the Laser Doppler signal to assess skin perfusion.

PubMed

Bagno, Andrea; Martini, Romeo

2015-01-01

The hemodynamics of skin microcirculation can be clinically assessed by means of Laser Doppler Fluxmetry. Laser Doppler signals show periodic oscillations because of fluctuations of microvascular perfusion (flowmotion), which are sustained by contractions and relaxations of arteriolar walls rhythmically changing vessels diameter (vasomotion). The wavelet analysis applied to Laser Doppler signals displays six characteristic frequency intervals, from 0.005 to 2 Hz. Each interval is assigned to a specific structure of the cardiovascular system: heart, respiration, vascular myocites, sympathetic terminations, and endothelial cells (dependent and independent on nitric oxide). Therefore, mechanisms of skin perfusion can be investigated through wavelet analysis. In the present work, examples of methods and results of wavelet analysis applied to Laser Doppler signals are reported. Laser Doppler signals were acquired in two groups of patients to check possible changes in vascular activities, before and after occlusive reactive hyperaemia, and before and after revascularization.

Raman imaging to investigate ultrastructure and composition of plant cell walls: distribution of lignin and cellulose in black spruce wood (Picea mariana).

PubMed

Agarwal, Umesh P

2006-10-01

A detailed understanding of the structural organization of the cell wall of vascular plants is important from both the perspectives of plant biology and chemistry and of commercial utilization. A state-of-the-art 633-nm laser-based confocal Raman microscope was used to determine the distribution of cell wall components in the cross section of black spruce wood in situ. Chemical information from morphologically distinct cell wall regions was obtained and Raman images of lignin and cellulose spatial distribution were generated. While cell corner (CC) lignin concentration was the highest on average, lignin concentration in compound middle lamella (CmL) was not significantly different from that in secondary wall (S2 and S2-S3). Images generated using the 1,650 cm(-1) band showed that coniferaldehyde and coniferyl alcohol distribution followed that of lignin and no particular cell wall layer/region was therefore enriched in the ethylenic residue. In contrast, cellulose distribution showed the opposite pattern-low concentration in CC and CmL and high in S2 regions. Nevertheless, cellulose concentration varied significantly in some areas, and concentrations of both lignin and cellulose were high in other areas. Though intensity maps of lignin and cellulose distributions are currently interpreted solely in terms of concentration differences, the effect of orientation needs to be carefully considered to reveal the organization of the wood cell wall.

A new Late Devonian genus with seed plant affinities.

PubMed

Wang, Deming; Liu, Le

2015-02-26

Many ovules of Late Devonian (Famennian) seed plants have been well studied. However, because few taxa occur with anatomically preserved stems and/or petioles, the vascular system of these earliest spermatophytes is little understood and available data come mostly from Euramerica. There remains great controversy over the anatomical differentiation of Late Devonian and Carboniferous seed plant groups of Buteoxylonales, Calamopityales and Lyginopteridales. Protostele evolution of these early spermatophytes needs more research. A new taxon Yiduxylon trilobum gen. et sp. nov. with seed plant affinities has been discovered in the Upper Devonian (Famennian) Tizikou Formation of Hubei Province, China. It is represented by stems, helically arranged and bifurcate fronds with two orders of pinnae and planate pinnules. Both secondary pinnae and pinnules are borne alternately. Stems contain a small protostele with three primary xylem ribs possessing a single peripheral protoxylem strand. Thick secondary xylem displays multiseriate bordered pitting on the tangential and radial walls of the tracheids, and has biseriate to multiseriate and high rays. A narrow cortex consists of inner cortex without sclerotic nests and sparganum-type outer cortex with peripheral bands of vertically aligned sclerenchyma cells. Two leaf traces successively arise tangentially from each primary xylem rib and they divide once to produce four circular-oval traces in the stem cortex. Four vascular bundles occur in two C-shaped groups at each petiole base with ground tissue and peripheral bands of sclerenchyma cells. Yiduxylon justifies the assignment to a new genus mainly because of the protostele with protoxylem strands only near the periphery of primary xylem ribs, leaf trace origination and petiolar vascular supply structure. It shares many definitive characters with Calamopityales and Lyginopteridales, further underscoring the anatomical similarities among early seed plants. The primary vascular system, pycnoxylic-manoxylic secondary xylem with bordered pits on both tangential and radial walls of a tracheid and leaf trace divergence of Yiduxylon suggest transitional features between the early spermatophytes and ancestral aneurophyte progymnosperms.

Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders

PubMed Central

Brozovich, F.V.; Nicholson, C.J.; Degen, C.V.; Gao, Yuan Z.; Aggarwal, M.

2016-01-01

The smooth muscle cell directly drives the contraction of the vascular wall and hence regulates the size of the blood vessel lumen. We review here the current understanding of the molecular mechanisms by which agonists, therapeutics, and diseases regulate contractility of the vascular smooth muscle cell and we place this within the context of whole body function. We also discuss the implications for personalized medicine and highlight specific potential target molecules that may provide opportunities for the future development of new therapeutics to regulate vascular function. PMID:27037223

Manipulating the structure and mechanical properties of thermoplastic polyurethane/polycaprolactone hybrid small diameter vascular scaffolds fabricated via electrospinning using an assembled rotating collector.

PubMed

Mi, Hao-Yang; Jing, Xin; Yu, Emily; Wang, Xiaofeng; Li, Qian; Turng, Lih-Sheng

2018-02-01

The success of blood vessel transplants with vascular scaffolds (VSs) highly depends on their structure and mechanical properties. The fabrication of small diameter vascular scaffolds (SDVSs) mimicking the properties of native blood vessels has been a challenge. Herein, we propose a facile method to fabricate thermoplastic polyurethane (TPU)/polycaprolactone (PCL) hybrid SDVSs via electrospinning using a modified rotating collector. By varying the ratio between the TPU and the PCL, and changing the electrospinning volume, SDVSs with a wavy configuration and different properties could be obtained. Detailed investigation revealed that certain TPU/PCL hybrid SDVSs closely resembled the mechanical behaviors of blood vessels due to the presence of a wavy region and the combination of flexible TPU and rigid PCL, which mimicked the properties of elastin and collagen in blood vessels. The fabricated TPU/PCL SDVSs achieved lumen diameters of 1-3mm, wall thicknesses of 100-570µm, circumferential moduli of 1-6MPa, ultimate strengths of 2-8MPa, over 250% elongation-at-break values, toe regions of 5.3-9.4%, high recoverability, and compliances close to those of human veins. Moreover, these TPU/PCL SDVSs possessed sufficient suture retention strength and burst pressure to fulfill transplantation requirements and maintain normal blood flow. Human endothelial cell culture revealed good biocompatibility of the scaffolds, and cells were able to grow on the inner surface of the tubular scaffolds, indicating promising prospects for use as tissue-engineered vascular grafts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Segmentation of arterial vessel wall motion to sub-pixel resolution using M-mode ultrasound.

PubMed

Fancourt, Craig; Azer, Karim; Ramcharan, Sharmilee L; Bunzel, Michelle; Cambell, Barry R; Sachs, Jeffrey R; Walker, Matthew

2008-01-01

We describe a method for segmenting arterial vessel wall motion to sub-pixel resolution, using the returns from M-mode ultrasound. The technique involves measuring the spatial offset between all pairs of scans from their cross-correlation, converting the spatial offsets to relative wall motion through a global optimization, and finally translating from relative to absolute wall motion by interpolation over the M-mode image. The resulting detailed wall distension waveform has the potential to enhance existing vascular biomarkers, such as strain and compliance, as well as enable new ones.

Fibro-vascular coupling in the control of cochlear blood flow.

PubMed

Dai, Min; Shi, Xiaorui

2011-01-01

Transduction of sound in the cochlea is metabolically demanding. The lateral wall and hair cells are critically vulnerable to hypoxia, especially at high sound levels, and tight control over cochlear blood flow (CBF) is a physiological necessity. Yet despite the importance of CBF for hearing, consensus on what mechanisms are involved has not been obtained. We report on a local control mechanism for regulating inner ear blood flow involving fibrocyte signaling. Fibrocytes in the super-strial region are spatially distributed near pre-capillaries of the spiral ligament of the albino guinea pig cochlear lateral wall, as demonstrably shown in transmission electron microscope and confocal images. Immunohistochemical techniques reveal the inter-connected fibrocytes to be positive for Na+/K+ ATPase β1 and S100. The connected fibrocytes display more Ca(2+) signaling than other cells in the cochlear lateral wall as indicated by fluorescence of a Ca(2+) sensor, fluo-4. Elevation of Ca(2+) in fibrocytes, induced by photolytic uncaging of the divalent ion chelator o-nitrophenyl EGTA, results in propagation of a Ca(2+) signal to neighboring vascular cells and vasodilation in capillaries. Of more physiological significance, fibrocyte to vascular cell coupled signaling was found to mediate the sound stimulated increase in cochlear blood flow (CBF). Cyclooxygenase-1 (COX-1) was required for capillary dilation. The findings provide the first evidence that signaling between fibrocytes and vascular cells modulates CBF and is a key mechanism for meeting the cellular metabolic demand of increased sound activity.

Trapezius placement of implanted ports: understanding the procedure.

PubMed

Hill, Steve

Totally implantable vascular access devices (TIVADs) are indicated for intermittent long-term intravenous access. It is widely accepted within medical literature that TIVADs are associated with statistically significant lower infection rates than other central venous access devices. Typical sites for implantation are on the anterior chest wall, using the internal jugular, axillary, cephalic or a subclavian vein. This article follows on from a previous discussion of the benefits of this approach, which illustrated and examined clinical outcomes of trapezius-placement versus anterior chest wall placed ports, for patients with metastatic subcutaneous disease on the anterior chest wall. The procedure provides a unique challenge for the clinician. This article focuses on the process of trapezius port implantation, providing an illustrative guide to understand the procedure. Trapezius port placement is a viable option for patients for whom routine sites are excluded and who require long-term intermittent vascular access.

Molecular intravascular imaging approaches for atherosclerosis.

PubMed

Press, Marcella Calfon; Jaffer, Farouc A

2014-10-01

Coronary artery disease (CAD) is an inflammatory process that results in buildup of atherosclerosis, typically lipid-rich plaque in the arterial wall. Progressive narrowing of the vessel wall and subsequent plaque rupture can lead to myocardial infarction and death. Recent advances in intravascular fluorescence imaging techniques have provided exciting coronary artery-targeted platforms to further characterize the molecular changes that occur within the vascular wall as a result of atherosclerosis and following coronary stent-induced vascular injury. This review will summarize exciting recent developments in catheter-based imaging of coronary arterial-sized vessels; focusing on two-dimensional near-infrared fluorescence imaging (NIRF) molecular imaging technology as an approach to specifically identify inflammation and fibrin directly within coronary artery-sized vessels. Intravascular NIRF is anticipated to provide new insights into the in vivo biology underlying high-risk plaques, as well as high-risks stents prone to stent restenosis or stent thrombosis.

Skin integrated with perfusable vascular channels on a chip.

PubMed

Mori, Nobuhito; Morimoto, Yuya; Takeuchi, Shoji

2017-02-01

This paper describes a method for fabricating perfusable vascular channels coated with endothelial cells within a cultured skin-equivalent by fixing it to a culture device connected to an external pump and tubes. A histological analysis showed that vascular channels were constructed in the skin-equivalent, which showed a conventional dermal/epidermal morphology, and the endothelial cells formed tight junctions on the vascular channel wall. The barrier function of the skin-equivalent was also confirmed. Cell distribution analysis indicated that the vascular channels supplied nutrition to the skin-equivalent. Moreover, the feasibility of a skin-equivalent containing vascular channels as a model for studying vascular absorption was demonstrated by measuring test molecule permeation from the epidermal layer into the vascular channels. The results suggested that this skin-equivalent can be used for skin-on-a-chip applications including drug development, cosmetics testing, and studying skin biology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Advanced life systems hardware development for future missions

NASA Technical Reports Server (NTRS)

1975-01-01

An examination of the pulse formation in an externalized vessel suggests that the vessel does not behave as a simple visco-elastic tube. Pressure-pulse waveform transducers are sensitive either to the pressure present at the vessel wall or to the volume of blood filling a region of tissue. Results of comparisons between intra-and extra-vascular pressure recordings suggest that changes in vasomotor tone and transducer-vessel pressures may be the greatest contributors to the divergence of extra-vascular waveforms from intra-vascular waveforms.

Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

PubMed

Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

2018-04-12

Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Brain vascular lesions: a clinicopathologic, immunohistochemistry, and ultrastructural approach.

PubMed

Navarrete, Marisol Galván; Hernández, Alma Dalia; Collado-Ortiz, Miguel Angel; Salinas-Lara, Citlaltepetl; Tena-Suck, Martha Lilia

2014-08-01

Brain vascular malformations are relatively common lesions that cause serious neurologic disability or death in a significant proportion of individuals bearing them. The purpose of this study was to analyze the clinicopathologic and immunohistochemistry these lesions, looking for common antibodies expressed such as CD31, CD34, CD15, factor VIII, nestin, vimentin, vascular endothelial grow factor (VEGF), vascular endothelial grow factor receptor-2 (VEGF-R2), glial fibrillar acidic protien (GFAP), and fibroblastic grow factor β (β-FGF) and ultrastructure in endothelial cells as well as in vessel walls. Fifty cases of vascular lesions were included in this study: 29 (58%) of them were arteriovenous malformations and 21 (52%) were brain cavernomas. Twenty-six (52%) patients were women and 24 (48%) men. The age range was from 13 to 68 years (mean age, 35.86 ± 15.19 years). The size of the lesions ranged between 1 and 8 cm (3 ± 1.65 cm), and parieto-occipital lesions had a bigger size. Evolution time varied from 1 month to 1 year (mean, 7.5 months). There was a significant statistical correlation between age and sex (P = -035), rupture of lesion (P = .015), brain hemorrhage (P = .033), necrosis (P = .011), hemosiderin deposit (P = .042), VEGF (P = .015), and VEGFR (P = .037), as well as localization of rupture (P = .017), loss of consciousness (P = .000), visual deficit (P = .026), hyaline vessels (P = .000), and CD31 (.009). Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in blood vessel walls have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function in brain vascular lesions. However, the molecular mechanisms that underlie the formation and growth of brain arteriovenous malformations are still poorly understood. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic and environmental modification of the mechanical properties of wood

NASA Astrophysics Data System (ADS)

Sederoff, R.; Allona, I.; Whetten, R.

1996-02-01

Wood is one of the nation's leading raw materials and is used for a wide variety of products, either directly as wood, or as derived materials in pulp and paper. Wood is a biological material and evolved to provide mechanical support and water transport to the early plants that conquered the land. Wood is a tissue that results from the differentiation and programmed cell death of cells that derive from a tissue known as the vascular cambium. The vascular cambium is a thin cylinder of undifferentiated tissue in plant stems and roots that gives rise to several different cell types. Cells that differentiate on the internal side of the cambium form xylem, a tissue composed in major part, of long thin cells that die leaving a network of interconnected cell walls that serve to transport water and to provide mechanical support for the woody plant. The shape and chemical composition of the cells in xylem are well suited for these functions. The structure of cells in xylem determines the mechanical properties of the wood because of the strength derived from the reinforced matrix of the wall. The hydrophobic phenolic surface of the inside of the cell walls is essential to maintain surface tension upon which water transport is based and to resist decay caused by microorganisms. The properties of wood derived from the function of xylem also determine its structural and chemical properties as wood and paper products. Therefore, the physical and chemical properties of wood and paper products also depend on the morphology and composition of the cells from which they are derived. Wood (xylem cell walls) is an anisotropic material, a composite of lignocellulose. It is a matrix of cellulose microfibrils, complexed with hemicelluloses, (carbohydrate polymers which contain sugars other than glucose, both pentoses and hexoses), embedded together in a phenolic matrix of lignin. The high tensile strength of wood in the longitudinal direction, is due to the structure of cellulose and the orientation of the cellulose microfibrils. Lignin provides the embedding matrix that imparts compressive strength and flexibility. The water conducting cells in xylem, the tracheids, are long thin cells, which become the fibers of paper when the lignin is removed from wood during the papermaking process. The length of the tracheids and the thickness of the walls have important effects on the properties of paper that is produced. The past two decades have marked a revolutionary period in biological sciences due to the development of gene splicing techniques. These methods have led to the directed engineering of organisms to develop new industrial products. The technology has been used to produce a wide variety of new pharmaceuticals and transgenic plants and animals. This technology is now also being applied to forest trees.

Role of Glyceraldehyde-Derived AGEs and Mitochondria in Superoxide Production in Femoral Artery of OLETF Rat and Effects of Pravastatin.

PubMed

Hori, Eisei; Kikuchi, Chigusa; Nagami, Chie; Kajikuri, Junko; Itoh, Takeo; Takeuchi, Masayoshi; Matsunaga, Tamihide

2017-11-01

A complication of diabetes mellitus is the over-production of vascular superoxides, which contribute to the development of arteriosclerosis and peripheral arterial disease (PAD). Hyperglycemia induces the formation and accumulation of advanced glycation end-products (AGEs), which in turn stimulate vascular superoxide production. The mechanism underlying AGE-mediated vascular superoxide production remains to be clarified in lower limb complications associated with diabetes. In the present study, we investigated the role of AGEs and the mitochondrial respiratory complex in superoxide production in femoral arteries using the type 2 diabetes model Otsuka Long-Evans Tokushima Fatty (OLETF) rats [vs. non-diabetic Long-Evans Tokushima Otsuka (LETO) rats]. The effects of in vivo administration of pravastatin on superoxide production in femoral arteries were also examined. Using chemiluminescent assays, luminescence microscopy, and competitive enzyme-linked immunosorbent assay (ELISA), we determined that vascular superoxide production and serum glyceraldehyde-derived AGEs (Glycer-AGEs) increased in OLETF rats. Pravastatin inhibited these responses without changing serum total cholesterol concentrations. The mitochondrial complex II inhibitor thenoyltrifluoroacetone (TTFA) also inhibited vascular superoxide production. Application of Glycer-AGEs in situ increased superoxide production in the vascular wall of femoral arteries from pravastatin-treated OLETF rats, which was then inhibited by TTFA. These results suggest that hyperglycemia increases serum Glycer-AGEs, which subsequently induce superoxide production in the femoral artery of OLETF rats in a mitochondrial complex II-dependent manner. Collectively, our results have partially elucidated the pathological mechanisms leading to diabetes-related PAD, and indicate dual beneficial actions of pravastatin for the prevention of oxidative damage to the vascular wall.

Induction of vascular endothelial phenotype and cellular proliferation from human cord blood stem cells cultured in simulated microgravity

NASA Astrophysics Data System (ADS)

Chiu, Brian; Z-M Wan, Jim; Abley, Doris; Akabutu, John

2005-05-01

Recent studies have demonstrated that stem cells derived from adult hematopoietic tissues are capable of trans-differentiation into non-hematopoietic cells, and that the culture in microgravity ( μg) may modulate the proliferation and differentiation. We investigated the application of μg to human umbilical cord blood stem cells (CBSC) in the induction of vascular endothelial phenotype expression and cellular proliferation. CD34+ mononuclear cells were isolated from waste human umbilical cord blood samples and cultured in simulated μg for 14 days. The cells were seeded in rotary wall vessels (RWV) with or without microcarrier beads (MCB) and vascular endothelial growth factor was added during culture. Controls consisted of culture in 1 G. The cell cultures in RWV were examined by inverted microscopy. Cell counts, endothelial cell and leukocyte markers performed by flow-cytometry and FACS scan were assayed at days 1, 4, 7 and at the termination of the experiments. Culture in RWV revealed significantly increased cellular proliferation with three-dimensional (3D) tissue-like aggregates. At day 4, CD34+ cells cultured in RWV bioreactor without MCB developed vascular tubular assemblies and exhibited endothelial phenotypic markers. These data suggest that CD34+ human umbilical cord blood progenitors are capable of trans-differentiation into vascular endothelial cell phenotype and assemble into 3D tissue structures. Culture of CBSC in simulated μg may be potentially beneficial in the fields of stem cell biology and somatic cell therapy.

Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia

NASA Astrophysics Data System (ADS)

Minamino, Tohru; Christou, Helen; Hsieh, Chung-Ming; Liu, Yuxiang; Dhawan, Vijender; Abraham, Nader G.; Perrella, Mark A.; Mitsialis, S. Alex; Kourembanas, Stella

2001-07-01

Chronic hypoxia causes pulmonary hypertension with smooth muscle cell proliferation and matrix deposition in the wall of the pulmonary arterioles. We demonstrate here that hypoxia also induces a pronounced inflammation in the lung before the structural changes of the vessel wall. The proinflammatory action of hypoxia is mediated by the induction of distinct cytokines and chemokines and is independent of tumor necrosis factor- signaling. We have previously proposed a crucial role for heme oxygenase-1 (HO-1) in protecting cardiomyocytes from hypoxic stress, and potent anti-inflammatory properties of HO-1 have been reported in models of tissue injury. We thus established transgenic mice that constitutively express HO-1 in the lung and exposed them to chronic hypoxia. HO-1 transgenic mice were protected from the development of both pulmonary inflammation as well as hypertension and vessel wall hypertrophy induced by hypoxia. Significantly, the hypoxic induction of proinflammatory cytokines and chemokines was suppressed in HO-1 transgenic mice. Our findings suggest an important protective function of enzymatic products of HO-1 activity as inhibitors of hypoxia-induced vasoconstrictive and proinflammatory pathways.

Paradigm shift regarding the transversalis fascia, preperitoneal space, and Retzius' space.

PubMed

Asakage, N

2018-06-01

There has been confusion in the anatomical recognition when performing inguinal hernia operations in Japan. From now on, a paradigm shift from the concept of two-dimensional layer structure to the three-dimensional space recognition is necessary to promote an understanding of anatomy. Along with the formation of the abdominal wall, the extraperitoneal space is formed by the transversalis fascia and preperitoneal space. The transversalis fascia is a somatic vascular fascia originating from an arteriovenous fascia. It is a dense areolar tissue layer at the outermost of the extraperitoneal space that runs under the diaphragm and widely lines the body wall muscle. The umbilical funiculus is taken into the abdominal wall and transformed into the preperitoneal space that is a local three-dimensional cavity enveloping preperitoneal fasciae composed of the renal fascia, vesicohypogastric fascia, and testiculoeferential fascia. The Retzius' space is an artificial cavity formed at the boundary between the transversalis fascia and preperitoneal space. In the underlay mesh repair, the mesh expands in the range spanning across the Retzius' space and preperitoneal space.

Physical Factors Effecting Cerebral Aneurysm Pathophysiology

PubMed Central

Sadasivan, Chander; Fiorella, David J.; Woo, Henry H.; Lieber, Baruch B.

2013-01-01

Many factors that are either blood-, wall-, or hemodynamics-borne have been associated with the initiation, growth, and rupture of intracranial aneurysms. The distribution of cerebral aneurysms around the bifurcations of the circle of Willis has provided the impetus for numerous studies trying to link hemodynamic factors (flow impingement, pressure, and/or wall shear stress) to aneurysm pathophysiology. The focus of this review is to provide a broad overview of such hemodynamic associations as well as the subsumed aspects of vascular anatomy and wall structure. Hemodynamic factors seem to be correlated to the distribution of aneurysms on the intracranial arterial tree and complex, slow flow patterns seem to be associated with aneurysm growth and rupture. However, both the prevalence of aneurysms in the general population and the incidence of ruptures in the aneurysm population are extremely low. This suggests that hemodynamic factors and purely mechanical explanations by themselves may serve as necessary, but never as necessary and sufficient conditions of this disease’s causation. The ultimate cause is not yet known, but it is likely an additive or multiplicative effect of a handful of biochemical and biomechanical factors. PMID:23549899

[Oxygen-dependent processes in the blood cells from children with arterial hypertension concomitant with biliary dyskinesia].

PubMed

Mikashinovich, Z I; Nagornaia, G Iu; Kovalenko, T D; Zvereva, E A

2011-02-01

Age individuality is characterized by an imbalance of the molecular mechanisms of antioxidant defense in adolescents with arterial hypertension and biliary dyskinesia, as documented by an enzyme imbalance of the first line of antioxidant defense and H2O, accumulation, by a substantial increase in glutathione peroxidase activity, and by inhibition of the activity of glutathione-dependent enzymes. The considerable rise of 2,3-diphosphoglycerate suggests tissue hypoxia. With this, enhanced neutrophil elastase activity causes damage to the structural components of vascular wall connective tissue, resulting in the development of endothelial dysfunction.

Smooth muscle-dependent changes in aortic wall dynamics during intra-aortic counterpulsation in an animal model of acute heart failure.

PubMed

Cabrera Fischer, Edmundo I; Bia, Daniel; Zócalo, Yanina; Armentano, Ricardo L

2009-06-01

Intra-aortic balloon pumping (IABP) may modify arterial biomechanics; however, its effects on arterial wall properties during acute cardio-depression have not yet been fully explored. This dynamical study was designed to characterize the effects of IABP on aortic wall mechanics in an in vivo animal model of acute heart failure. Aortic pressure, diameter and blood flow were measured in six anesthetized sheep with acute cardio-depression by halothane (4%), before and during IABP (1:2). Aortic characteristic impedance and aortic wall stiffness indexes were calculated. acute experimental cardio-depression resulted in a reduction in mean aortic pressure (p<0.05) and an increase in the characteristic impedance (p<0.005), incremental elastic modulus (p<0.05), stiffness index (p<0.05) and Peterson elastic modulus (p<0.05). IABP caused an increase in the cardiac output (p<0.005) and a reduction in the systemic vascular resistances (p<0.05). In addition, the aortic impedance, incremental elastic modulus, stiffness index and Peterson modulus were significantly reduced during IABP (p<0.05). Our findings show that IABP caused changes in aortic wall impedance and intrinsic wall properties, improving the arterial functional capability and the left ventricular afterload by a reduction in both. Systemic vascular resistances and aortic stiffness were also improved by means of smooth muscle-dependent mechanisms.

The βI-galactosidase of Cicer arietinum is located in thickened cell walls such as those of collenchyma, sclerenchyma and vascular tissue.

PubMed

Martín, I; Jiménez, T; Hernández-Nistal, J; Dopico, B; Labrador, E

2011-09-01

We report localisation of the chickpea βI-Gal, a member of the chickpea β-galactosidase family, which contains at least four members. After generation of specific antibodies, the distribution and cellular immunolocalisation of the protein in different organs and developmental stages of the plant was studied. βI-Gal protein is much longer than the other chickpea β-galactosidases because of the presence of a lectin-like domain in the carboxyl terminus of the protein. Western blot experiments indicated that the active βI-Gal retains this lectin-like domain for its function in the plant. The βI-Gal protein was mainly detected in cell walls of elongating organs, such as seedling epicotyls and stem internodes. An immunolocation study indicated a very good correlation between the presence of this βΙ-galactosidase and cells whose walls are thickening, not only in aged epicotyls and mature internodes in the final phase of elongation, but mostly in cells with a support function, such as collenchyma cells, xylem and phloem fibres and a layer of sclerenchyma cells surrounding the vascular cylinder (perivascular fibres). These results could suggest a function for the βI-Gal in modification of cell wall polymers, leading to thicker walls than the primary cell walls. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

Zone-specific remodeling of tumor blood vessels affects tumor growth.

PubMed

Tilki, Derya; Kilic, Nerbil; Sevinc, Sema; Zywietz, Friedrich; Stief, Christian G; Ergun, Suleyman

2007-11-15

Chaotic organization, abnormal leakiness, and structural instability are characteristics of tumor vessels. However, morphologic events of vascular remodeling in relation to tumor growth are not sufficiently studied yet. By using the rat rhabdomyosarcoma tumor model vascular morphogenesis was studied by light and electron microscopy and immunohistochemistry in relation to tumor regions such as tumor surrounding (TSZ), marginal (TMZ), intermediate (TIZ), and center (TCZ) zones. The analyses revealed that blood vessels of TSZ display a regular ultrastructure, whereas blood vessels of TMZ showed a chaotic organization and unstable structure with a diffuse or even lacking basal lamina, and missing or irregular assembled periendothelial cells. In contrast, blood vessels of TIZ and TCZ exhibited a more or less stabilized vessel structure with increased diameter. Correspondingly, normal assembly of alpha-smooth-muscle-actin (alpha-SMA)-positive cells into the vessel wall was observed in blood vessels of TSZ, TIZ, and TCZ. Also, Ang1 immunostaining was strongest in large vessels of TIZ and TCZ, whereas Ang2 staining was prominent in small vessels of TIZ. Tie2 staining was detectable in small and large vessels of all tumor zones. Immunostaining for alpha(v)beta(3)-integrin was strongest in small vessels of TMZ, whereas large vessels of TIZ and TCZ were almost negative. The results indicate a zone-specific remodeling of tumor blood vessels by stabilization of vessels in TIZ and TCZ, whereas small vessels of these zones obviously undergo regression leading to tumor necrosis. Thus, a better understanding of vascular remodeling and stabilization in tumors would enable new strategies in tumor therapy and imaging. (c) 2007 American Cancer Society.

Estimation of the physiological mechanical conditioning in vascular tissue engineering by a predictive fluid-structure interaction approach.

PubMed

Tresoldi, Claudia; Bianchi, Elena; Pellegata, Alessandro Filippo; Dubini, Gabriele; Mantero, Sara

2017-08-01

The in vitro replication of physiological mechanical conditioning through bioreactors plays a crucial role in the development of functional Small-Caliber Tissue-Engineered Blood Vessels. An in silico scaffold-specific model under pulsatile perfusion provided by a bioreactor was implemented using a fluid-structure interaction (FSI) approach for viscoelastic tubular scaffolds (e.g. decellularized swine arteries, DSA). Results of working pressures, circumferential deformations, and wall shear stress on DSA fell within the desired physiological range and indicated the ability of this model to correctly predict the mechanical conditioning acting on the cells-scaffold system. Consequently, the FSI model allowed us to a priori define the stimulation pattern, driving in vitro physiological maturation of scaffolds, especially with viscoelastic properties.

Redox signaling, Nox5 and vascular remodeling in hypertension.

PubMed

Montezano, Augusto C; Tsiropoulou, Sofia; Dulak-Lis, Maria; Harvey, Adam; Camargo, Livia De Lucca; Touyz, Rhian M

2015-09-01

Extensive data indicate a role for reactive oxygen species (ROS) and redox signaling in vascular damage in hypertension. However, molecular mechanisms underlying these processes remain unclear, but oxidative post-translational modification of vascular proteins is critical. This review discusses how proteins are oxidatively modified and how redox signaling influences vascular smooth muscle cell growth and vascular remodeling in hypertension. We also highlight Nox5 as a novel vascular ROS-generating oxidase. Oxidative stress in hypertension leads to oxidative imbalance that affects vascular cell function through redox signaling. Many Nox isoforms produce ROS in the vascular wall, and recent findings show that Nox5 may be important in humans. ROS regulate signaling by numerous processes including cysteine oxidative post-translational modification such as S-nitrosylation, S-glutathionylation and sulfydration. In vascular smooth muscle cells, this influences cellular responses to oxidative stimuli promoting changes from a contractile to a proliferative phenotype. In hypertension, Nox-induced ROS production is increased, leading to perturbed redox signaling through oxidative modifications of vascular proteins. This influences mitogenic signaling and cell cycle regulation, leading to altered cell growth and vascular remodeling in hypertension.

High wall shear stress and spatial gradients in vascular pathology: a review.

PubMed

Dolan, Jennifer M; Kolega, John; Meng, Hui

2013-07-01

Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.

Losartan attenuates vascular remodeling of the aorta in spontaneously hypertensive rats and the underlying mechanism.

PubMed

Li, Fangxiong; Shi, Ruizheng; Liao, Meichun; Li, Jianzhe; Li, Shixun; Pan, Wei; Yang, Tianlun; Zhang, Guogang

2010-08-01

To determine the effect of losartan on vascular remodeling and the underlying mechanism in spontaneously hypertensive rats(SHR). SHR of 12 weeks old were given losartan orally [0, 15, 30 mg/(kg.d), n=12]. The tail arterial pressure was measured every week. Eight weeks later, the pathological changes and p22(phox) expression in the thoracic aorta, the activity of catalase (CAT), the contents of H(2)O(2) and Ang II in the plasma were evaluated. Blood pressure was increased in the SHR accompanied by the thickened wall and increased p22(phox) expression in the thoracic aorta. The plasma levels of H(2)O(2) and Ang II were elevated while the CAT level was decreased in the SHR. Administration of losartan reversed the thickened wall and increased the CAT activity concomitantly with the decreased plasma levels of H(2)O(2) and p22(phox) expression in the SHR. The plasma level of Ang II increased after the losartan treatment. Oxidative stress induces the vascular remodeling of the aorta in the SHR. Losartan can reverse the vascular remodeling through down-regulating p22(phox) expression and inhibiting the oxidative stress.

Reducing the data: Analysis of the role of vascular geometry on blood flow patterns in curved vessels

NASA Astrophysics Data System (ADS)

Alastruey, Jordi; Siggers, Jennifer H.; Peiffer, Véronique; Doorly, Denis J.; Sherwin, Spencer J.

2012-03-01

Three-dimensional simulations of blood flow usually produce such large quantities of data that they are unlikely to be of clinical use unless methods are available to simplify our understanding of the flow dynamics. We present a new method to investigate the mechanisms by which vascular curvature and torsion affect blood flow, and we apply it to the steady-state flow in single bends, helices, double bends, and a rabbit thoracic aorta based on image data. By calculating forces and accelerations in an orthogonal coordinate system following the centreline of each vessel, we obtain the inertial forces (centrifugal, Coriolis, and torsional) explicitly, which directly depend on vascular curvature and torsion. We then analyse the individual roles of the inertial, pressure gradient, and viscous forces on the patterns of primary and secondary velocities, vortical structures, and wall stresses in each cross section. We also consider cross-sectional averages of the in-plane components of these forces, which can be thought of as reducing the dynamics of secondary flows onto the vessel centreline. At Reynolds numbers between 50 and 500, secondary motions in the directions of the local normals and binormals behave as two underdamped oscillators. These oscillate around the fully developed state and are coupled by torsional forces that break the symmetry of the flow. Secondary flows are driven by the centrifugal and torsional forces, and these are counterbalanced by the in-plane pressure gradients generated by the wall reaction. The viscous force primarily opposes the pressure gradient, rather than the inertial forces. In the axial direction, and depending on the secondary motion, the curvature-dependent Coriolis force can either enhance or oppose the bulk of the axial flow, and this shapes the velocity profile. For bends with little or no torsion, the Coriolis force tends to restore flow axisymmetry. The maximum circumferential and axial wall shear stresses along the centreline correlate well with the averaged in-plane pressure gradient and the radial displacement of the peak axial velocity, respectively. We conclude with a discussion of the physiological implications of these results.

A comparative genome analysis of PME and PMEI families reveals the evolution of pectin metabolism in plant cell walls.

PubMed

Wang, Maojun; Yuan, Daojun; Gao, Wenhui; Li, Yang; Tan, Jiafu; Zhang, Xianlong

2013-01-01

Pectins are fundamental polysaccharides in the plant primary cell wall. Pectins are synthesized and secreted to cell walls as highly methyl-esterified polymers and then demethyl-esterified by pectin methylesterases (PMEs), which are spatially regulated by pectin methylesterase inhibitors (PMEIs). Although PME and PMEI genes are pivotal in plant cell wall formation, few studies have focused on the evolutionary patterns of the PME and PMEI gene families. In this study, the gene origin, evolution, and expression diversity of these two families were systematically analyzed using 11 representative species, including algae, bryophytes, lycophytes and flowering land plants. The results show that 1) for the two subfamilies (PME and proPME) of PME, the origin of the PME subfamily is consistent with the appearance of pectins in early charophyte cell walls, 2) Whole genome duplication (WGD) and tandem duplication contribute to the expansion of proPME and PMEI families in land plants, 3) Evidence of selection pressure shows that the proPME and PMEI families have rapidly evolved, particularly the PMEI family in vascular plants, and 4) Comparative expression profile analysis of the two families indicates that the eudicot Arabidopsis and monocot rice have different expression patterns. In addition, the gene structure and sequence analyses show that the origin of the PMEI domain may be derived from the neofunctionalization of the pro domain after WGD. This study will advance the evolutionary understanding of the PME and PMEI families and plant cell wall development.

Cell Wall Modifications in Arabidopsis Plants with Altered α-l-Arabinofuranosidase Activity[C][W

PubMed Central

Chávez Montes, Ricardo A.; Ranocha, Philippe; Martinez, Yves; Minic, Zoran; Jouanin, Lise; Marquis, Mélanie; Saulnier, Luc; Fulton, Lynette M.; Cobbett, Christopher S.; Bitton, Frédérique; Renou, Jean-Pierre; Jauneau, Alain; Goffner, Deborah

2008-01-01

Although cell wall remodeling is an essential feature of plant growth and development, the underlying molecular mechanisms are poorly understood. This work describes the characterization of Arabidopsis (Arabidopsis thaliana) plants with altered expression of ARAF1, a bifunctional α-l-arabinofuranosidase/β-d-xylosidase (At3g10740) belonging to family 51 glycosyl-hydrolases. ARAF1 was localized in several cell types in the vascular system of roots and stems, including xylem vessels and parenchyma cells surrounding the vessels, the cambium, and the phloem. araf1 T-DNA insertional mutants showed no visible phenotype, whereas transgenic plants that overexpressed ARAF1 exhibited a delay in inflorescence emergence and altered stem architecture. Although global monosaccharide analysis indicated only slight differences in cell wall composition in both mutant and overexpressing lines, immunolocalization experiments using anti-arabinan (LM6) and anti-xylan (LM10) antibodies indicated cell type-specific alterations in cell wall structure. In araf1 mutants, an increase in LM6 signal intensity was observed in the phloem, cambium, and xylem parenchyma in stems and roots, largely coinciding with ARAF1 expression sites. The ectopic overexpression of ARAF1 resulted in an increase in LM10 labeling in the secondary walls of interfascicular fibers and xylem vessels. The combined ARAF1 gene expression and immunolocalization studies suggest that arabinan-containing pectins are potential in vivo substrates of ARAF1 in Arabidopsis. PMID:18344421

In vitro experiments of vessel wall apposition between the Enterprise and Enterprise 2 stents for treatment of cerebral aneurysms.

PubMed

Kono, Kenichi; Terada, Tomoaki

2016-02-01

A closed-cell stent called Enterprise has been used for stent-assisted coil embolization of cerebral aneurysms. The Enterprise stent tends to cause kinks and vessel wall malposition in curved vessels and may cause thromboembolic complications. We evaluated vessel wall apposition of a new closed-cell stent, Enterprise 2, compared with a previous Enterprise stent, using curved vascular silicone models. The Enterprise or Enterprise 2 stent was deployed in curved vascular models with various radii of approximately 5 to 10 mm. Stent deployment was performed 25 times in each stent. A push-pull technique was used to minimize incomplete wall apposition. To evaluate conformity of stents, gaps between a stent and a vessel wall were measured. The gap ratio (gap / a wall diameter) was 15 % ± 17 % (mean ± standard deviation) and 41 % ± 15 % with the Enterprise 2 stent and the Enterprise stent, respectively. Taking gap ratios and radii of vessel curvature into consideration, the Enterprise 2 stent had significantly better wall apposition than the Enterprise stent (p = 0.005). In the same radius of vessel curvature, the Enterprise 2 stent had approximately half of the gap compared with the Enterprise stent. There were no significant differences in vessel straightening effects between the two stents. The Enterprise 2 stent has better wall apposition in curved vessels than the Enterprise stent. The gap between a vessel wall and the Enterprise 2 stent is approximately half that of the Enterprise stent. However, gaps and kinks are still present in curved vessels with a small radius. Caution should be taken for kinks and malposition in acutely curved vessels, such as the siphon of the internal carotid artery.

in silico Vascular Modeling for Personalized Nanoparticle Delivery

PubMed Central

Hossain, Shaolie S.; Zhang, Yongjie; Liang, Xinghua; Hussain, Fazle; Ferrari, Mauro; Hughes, Thomas J. R.; Decuzzi, Paolo

2013-01-01

Aims To predict the deposition of nanoparticles in a patient-specific arterial tree as a function of the vascular architecture, flow conditions, receptor surface density, and nanoparticle properties. Materials & methods The patient-specific vascular geometry is reconstructed from CT Angiography images. The Isogeometric Analysis framework integrated with a special boundary condition for the firm wall adhesion of nanoparticles is implemented. A parallel plate flow chamber system is used to validate the computational model in vitro. Results Particle adhesion is dramatically affected by changes in patient-specific attributes, such as branching angle and receptor density. The adhesion pattern correlates well with the spatial and temporal distribution of the wall shear rates. For the case considered, the larger (2.0 μm) particles adhere ≈ 2 times more in the lower branches of the arterial tree, whereas the smaller (0.5 μm) particles deposit more in the upper branches. Conclusion Our computational framework in conjunction with patient specific attributes can be used to rationally select nanoparticle properties to personalize, thus optimize, therapeutic interventions. PMID:23199308

Transactivation of ErbB receptors by leptin in the cardiovascular system: mechanisms, consequences and target for therapy.

PubMed

Bełtowski, Jerzy; Jazmroz-Wiśniewska, Anna

2014-01-01

Many experimental and clinical studies have demonstrated that elevated leptin concentration in patients with obesity/metabolic syndrome contributes to the pathogenesis of cardiovascular disorders including arterial hypertension, atherosclerosis, restenosis after coronary angioplasty and myocardial hypertrophy. Receptor tyrosine kinases belonging to the ErbB family, especially ErbB1 (epidermal growth factor receptor) and ErbB2 are abundantly expressed in the blood vessels and the heart. EGFR is activated not only by its multiple peptide ligands but also by many other factors including angiotensin II, endothelin-1, norepinephrine, thrombin and prorenin; the phenomenon referred to as "transactivation". Augmented EGFR signaling contributes to abnormalities of vascular tone and renal sodium handling as well as vascular remodeling and myocardial hypertrophy through various intracellular mechanisms, in particular extracellular signal-regulated kinases (ERK) and phosphoinositide 3-kinase (PI3K). Recent experimental studies indicate that chronically elevated leptin transactivates the EGFR through the mechanisms requiring reactive oxygen species and cytosolic tyrosine kinase, c-Src. In addition, hyperleptinemia increases ErbB2 activity in the arterial wall. Stimulation of EGFR and ErbB2 downstream signaling pathways such as ERK and PI3K in the vascular wall and the kidney may contribute to the increase in vascular tone, enhanced tubular sodium reabsorption as well as vascular and renal lesions in hyperleptinemic obese subjects.

UAP56 is an important mediator of Angiotensin II/platelet derived growth factor induced vascular smooth muscle cell DNA synthesis and proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahni, Abha; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555; Wang, Nadan

2013-02-15

Highlights: ► Knockdown of UAP56 inhibits Angiotensin II/PDGF induced vascular smooth muscle cell proliferation. ► UAP56 is a positive regulator of E2F transcriptional activation. ► UAP56 is present in the vessel wall of low flow carotid arteries. -- Abstract: Angiotensin (Ang) II and platelet-derived growth factor (PDGF) are important mediators of pathologic vascular smooth muscle cell (VSMC) proliferation. Identifying downstream mediators of Ang II and PDGF signaling may provide insights for therapies to improve vascular proliferative diseases. We have previously demonstrated that breakpoint cluster region (Bcr) is an important mediator of Ang II/PDGF signaling in VSMC. We have recently reportedmore » that the DExD/H box protein UAP56 is an interacting partner of Bcr in regulating VSMC DNA synthesis. We hypothesized that UAP56 itself is an important regulator of VSMC proliferation. In this report we demonstrate that knockdown of UAP56 inhibits Ang II/PDGF induced VSMC DNA synthesis and proliferation, and inhibits E2F transcriptional activity. In addition, we demonstrate that UAP56 is present in the vessel wall of low-flow carotid arteries. These findings suggest that UAP56 is a regulator of VSMC proliferation and identify UAP56 as a target for preventing vascular proliferative disease.« less

Bioactive surface modifications on inner walls of poly-tetra-fluoro-ethylene tubes using dielectric barrier discharge

NASA Astrophysics Data System (ADS)

Cho, Yong Ki; Park, Daewon; Kim, Hoonbae; Lee, Hyerim; Park, Heonyong; Kim, Hong Ja; Jung, Donggeun

2014-03-01

Bioactive surface modification can be used in a variety of medical polymeric materials in the fields of biochips and biosensors, artificial membranes, and vascular grafts. In this study, the surface modification of the inner walls of poly-tetra-fluoro-ethylene (PTFE) tubing was carried out to improve vascular grafts, which are made of biocompatible material for the human body in the medical field. Focus was centered on the cell attachment of the inner wall of the PTFE by sequential processes of hydrogen plasma treatment, hydrocarbon deposition, and reactive plasma treatment on the PFTE surface using micro plasma discharge. Micro plasma was generated by a medium-frequency alternating current high-voltage generator. The preliminary modification of PTFE was conducted by a plasma of hydrogen and argon gases. The hydrocarbon thin film was deposited on modified PTFE with a mixture of acetylene and argon gases. The reactive plasma treatment using oxygen plasma was done to give biocompatible functionality to the inner wall surface. The hydrophobic surface of bare PTFE is made hydrophilic by the reactive plasma treatment due to the formation of carbonyl groups on the surface. The reactive treatment could lead to improved attachment of smooth muscle cells (SMCs) on the modified PTFE tubing. Fourier transform infrared absorption spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and water contact angle measurement were used for the analysis of the surface modification. The SMC-attached PTFE tube developed will be applicable to in vitro human vasculature-mimetic model systems, and to medical vascular grafts.

Vascular cemeteries formed by biological nanoparticles

NASA Astrophysics Data System (ADS)

Sommer, Andrei P.; Tsurumoto, Toshiyuki

2013-04-01

We report the discovery of dense colonies of globular structures ranging from 100 nm to 5 μm in the tunica media of the femoral artery of an 89-year-old female cadaver. Systematic analysis using scanning electron microscopy, energy dispersive X-ray spectroscopy and light microscopy reveals that the globular structures are surrounded by vascular smooth muscle cells (VSMCs) and consist predominantly of calcium phosphate. Inspection of the images suggests the action of two complementary growth processes. The structures may grow both in size and in number locally by Ostwald ripening and a replicative route, respectively. Morphology in conjunction with the quality of their native growth niche suggests that they are different from nanocrystals released from apoptotic bodies. Their tendency to fill VSMC pockets leads to the speculation that they could represent an effort of the VSMC system to wall off cytotoxic nanocrystals liberated from apoptotic bodies. Alternatively, the structures may be equivalent with nanobacteria (NB)—a nomenclature which caused confusion. This is reflected by the multitude of names used by different authors for the nanoentities (living nanovesicles, nanobionta, calcifying nanoparticles, and nanons). Indeed, there is no clear definition in the literature as to what NB are. Considering that the calcium phosphate nanoparticles have been identified in the human body, we used in our study the descriptive name biological nanoparticles—the world's first nanoparticles.

Micro-engineering a platform to reconstruct physiology and functionality of the human brain microvasculature in vitro

NASA Astrophysics Data System (ADS)

Daghighi, Yasaman; Heidari, Hossein; Taylor, Hayden

2018-02-01

A predominant unsolved challenge in tissue engineering is the need of a robust technique for producing vascular networks, particularly when modeling human brain tissue. The availability of reliable in vitro human brain microvasculature models would advance our understanding of its function and would provide a platform for highthroughput drug screening. Current strategies for modeling vascularized brain tissue suffer from limitations such as (1) culturing non-human cell lines, (2) limited multi-cell co-culture, and (3) the effects of neighboring physiologically unrealistic rigid polymeric surfaces, such as solid membranes. We demonstrate a new micro-engineered platform that can address these shortcomings. Specifically, we have designed and prototyped a molding system to enable the precise casting of 100μm-diameter coaxial hydrogel structures laden with the requisite cells to mimic a vascular lumen. Here we demonstrate that a fine wire with diameter 130 μm or a needle with outer diameter 300 μm can be used as a temporary mold insert, and agarose-collagen composite matrix can be cast around these inserts and thermally gelled. When the wire or needle is retracted under the precise positional control afforded by our system, a microchannel is formed which is then seeded with human microvascular endothelial cells. After seven days of culture these cells produce an apparently confluent monolayer on the channel walls. In principle, this platform could be used to create multilayered cellular structures. By arranging a fine wire and a hollow needle coaxially, three distinct zones could be defined in the model: first, the bulk gel surrounding the needle; then, after needle retraction, a cylindrical shell of matrix; and finally, after retraction of the wire, a lumen. Each zone could be independently cell-seeded. To this end, we have also successfully 3D cultured human astrocytes and SY5Y glial cells in our agarose-collagen matrix. Our approach ultimately promises scalable and repeatable production of vascular structures with physiologically realistic mechanical properties.

Combination of Vessel-Targeting Agents and Fractionated Radiation Therapy: The Role of the SDF-1/CXCR4 Pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Fang-Hsin; Fu, Sheng-Yung; Yang, Ying-Chieh

2013-07-15

Purpose: To investigate vascular responses during fractionated radiation therapy (F-RT) and the effects of targeting pericytes or bone marrow-derived cells (BMDCs) on the efficacy of F-RT. Methods and Materials: Murine prostate TRAMP-C1 tumors were grown in control mice or mice transplanted with green fluorescent protein-tagged bone marrow (GFP-BM), and irradiated with 60 Gy in 15 fractions. Mice were also treated with gefitinib (an epidermal growth factor receptor inhibitor) or AMD3100 (a CXCR4 antagonist) to examine the effects of combination treatment. The responses of tumor vasculatures to these treatments and changes of tumor microenvironment were assessed. Results: After F-RT, the tumormore » microvascular density (MVD) was reduced; however, the surviving vessels were dilated, incorporated with GFP-positive cells, tightly adhered to pericytes, and well perfused with Hoechst 33342, suggesting a more mature structure formed primarily via vasculogenesis. Although the gefitinib+F-RT combination affected the vascular structure by dissociating pericytes from the vascular wall, it did not further delay tumor growth. These tumors had higher MVD and better vascular perfusion function, leading to less hypoxia and tumor necrosis. By contrast, the AMD3100+F-RT combination significantly enhanced tumor growth delay more than F-RT alone, and these tumors had lower MVD and poorer vascular perfusion function, resulting in increased hypoxia. These tumor vessels were rarely covered by pericytes and free of GFP-positive cells. Conclusions: Vasculogenesis is a major mechanism for tumor vessel survival during F-RT. Complex interactions occur between vessel-targeting agents and F-RT, and a synergistic effect may not always exist. To enhance F-RT, using CXCR4 inhibitor to block BM cell influx and the vasculogenesis process is a better strategy than targeting pericytes by epidermal growth factor receptor inhibitor.« less

Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser(1177)/Thr(497) of endothelial nitric oxide synthase in diabetic mice.

PubMed

Matsumoto, Sachiko; Shimabukuro, Michio; Fukuda, Daiju; Soeki, Takeshi; Yamakawa, Ken; Masuzaki, Hiroaki; Sata, Masataka

2014-01-31

Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), has a higher affinity for and slower dissociation from AT1 receptors and shows stronger inverse agonism compared to other ARBs. Possible benefits of azilsartan in diabetic vascular dysfunction have not been established. We measured vascular reactivity of aortic rings in male KKAy diabetic mice treated with vehicle, 0.005% azilsartan, or 0.005% candesartan cilexetil for 3 weeks. Expression of markers of inflammation and oxidative stress was measured using semiquantitative RT-PCR in the vascular wall, perivascular fat, and skeletal muscle. Phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 and Thr495 was measured using Western blotting, and the ratio of phosphorylation at Ser1177 to phosphorylation at Thr495 was used as a putative indicator of vascular eNOS activity. (1) Vascular endothelium-dependent relaxation with acetylcholine in KKAy mice was improved by azilsartan treatment compared to candesartan cilexetil; (2) the ratio of Ser1177/Thr495 phosphorylation of eNOS was impaired in KKAy and was effectively restored by azilsartan; (3) anomalies in the expression levels of monocyte chemotactic protein 1 (MCP1), F4/80, NAD(P)H oxidase (Nox) 2, and Nox4 of the aortic wall and in the expression of TNFα in the perivascular fat were strongly attenuated by azilsartan compared to candesartan cilexetil. These results provide evidence that azilsartan prevents endothelial dysfunction in diabetic mice, more potently than does candesartan cilexetil. Azilsartan's higher affinity for and slower dissociation from AT1 receptors may underlie its efficacy in diabetic vascular dysfunction via a dual effect on uncoupled eNOS and on Nox.

Automated measurement of retinal blood vessel tortuosity

NASA Astrophysics Data System (ADS)

Joshi, Vinayak; Reinhardt, Joseph M.; Abramoff, Michael D.

2010-03-01

Abnormalities in the vascular pattern of the retina are associated with retinal diseases and are also risk factors for systemic diseases, especially cardiovascular diseases. The three-dimensional retinal vascular pattern is mostly formed congenitally, but is then modified over life, in response to aging, vessel wall dystrophies and long term changes in blood flow and pressure. A characteristic of the vascular pattern that is appreciated by clinicians is vascular tortuosity, i.e. how curved or kinked a blood vessel, either vein or artery, appears along its course. We developed a new quantitative metric for vascular tortuosity, based on the vessel's angle of curvature, length of the curved vessel over its chord length (arc to chord ratio), number of curvature sign changes, and combined these into a unidimensional metric, Tortuosity Index (TI). In comparison to other published methods this method can estimate appropriate TI for vessels with constant curvature sign and vessels with equal arc to chord ratios, as well. We applied this method to a dataset of 15 digital fundus images of 8 patients with Facioscapulohumeral muscular dystrophy (FSHD), and to the other publically available dataset of 60 fundus images of normal cases and patients with hypertensive retinopathy, of which the arterial and venous tortuosities have also been graded by masked experts (ophthalmologists). The method produced exactly the same rank-ordered list of vessel tortuosity (TI) values as obtained by averaging the tortuosity grading given by 3 ophthalmologists for FSHD dataset and a list of TI values with high ranking correlation with the ophthalmologist's grading for the other dataset. Our results show that TI has potential to detect and evaluate abnormal retinal vascular structure in early diagnosis and prognosis of retinopathies.

Effect of PEGylation on ligand-based targeting of drug carriers to the vascular wall in blood flow.

PubMed

Onyskiw, Peter J; Eniola-Adefeso, Omolola

2013-09-03

The blood vessel wall plays a prominent role in the development of many life-threatening diseases and as such is an attractive target for treatment. To target diseased tissue, particulate drug carriers often have their surfaces modified with antibodies or epitopes specific to vascular wall-expressed molecules, along with poly(ethylene glycol) (PEG) to improve carrier blood circulation time. However, little is known about the effect of poly(ethylene glycol) on carrier adhesion dynamics-specifically in blood flow. Here we examine the influence of different molecular weight PEG spacers on particle adhesion in blood flow. Anti-ICAM-1 or Sialyl Lewis(a) were grafted onto polystyrene 2 μm and 500 nm spheres via PEG spacers and perfused in blood over activated endothelial cells at physiological shear conditions. PEG spacers were shown to improve, reduce, or have no effect on the binding density of targeted-carriers depending on the PEG surface conformation, shear rate, and targeting moiety.

Computational fluid dynamics tools can be used to predict the progression of coronary artery disease

NASA Astrophysics Data System (ADS)

Coşkun, A. Ümit; Chen, Caixia; Stone, Peter H.; Feldman, Charles L.

2006-03-01

Atherosclerosis is focal and individual plaques evolve in an independent manner. The endothelium regulates arterial behavior by responding to its local shear stress. In vitro studies indicate that low endothelial shear stress (ESS) upregulates the genetic and molecular responses leading to the initiation and progression of atherosclerosis and promotes inflammation and formation of other features characteristic of vulnerable plaque. Physiologic ESS is vasculoprotective and fosters quiescence of the endothelium and vascular wall. High ESS promotes platelet aggregation. ESS and vascular wall morphology along the course of human coronary arteries can now be characterized in vivo, and may predict the focal areas in which atherosclerosis progression occurs. Rapidly evolving methodologies are able to characterize the arterial wall and the local hemodynamic factors likely responsible for progression of coronary disease in man. These new diagnostic modalities allow for identification of plaque progression. Accurate identification of arterial segments at high-risk for progression may permit pre-emptive intervention strategies to avoid adverse coronary events.

Fluid Mechanics of the Vascular Basement Membrane in the Brain

NASA Astrophysics Data System (ADS)

Coloma, Mikhail; Hui, Jonathan; Chiarot, Paul; Huang, Peter; Carare, Roxana; McLeod, Kenneth; Schaffer, David

2013-11-01

Beta-amyloid is a normal product of brain metabolic function and is found within the interstitial fluid of the brain. Failure of the clearance of beta-amyloid from the aging brain leads to its accumulation within the walls of arteries and to Alzheimer's disease. The vascular basement membrane (VBM) within the walls of cerebral arteries surrounds the spirally arranged smooth muscle cells and represents an essential pathway for removal of beta-amyloid from the brain. This process fails with the stiffening of arterial walls associated with aging. In this study we hypothesize that the deformation of the VBM associated with arterial pulsations drives the interstitial fluid to drain in the direction opposite of the arterial blood flow. This hypothesis is theoretically investigated by modeling the VBM as a thin, coaxial, fluid-filled porous medium surrounding a periodically deforming cylindrical tube. Flow and boundary conditions required to achieve such a backward clearance are derived through a control volume analysis of mass, momentum, and energy.

A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions.

PubMed

van Engeland, Nicole C A; Pollet, Andreas M A O; den Toonder, Jaap M J; Bouten, Carlijn V C; Stassen, Oscar M J A; Sahlgren, Cecilia M

2018-05-29

Cell signalling and mechanics influence vascular pathophysiology and there is an increasing demand for in vitro model systems that enable examination of signalling between vascular cells under hemodynamic conditions. Current 3D vessel wall constructs do not recapitulate the mechanical conditions of the native tissue nor do they allow examination of cell-cell interactions under relevant hemodynamic conditions. Here, we describe a 3D microfluidic chip model of arterial endothelial and smooth muscle cells where cellular organization, composition and interactions, as well as the mechanical environment of the arterial wall are mimicked. The hemodynamic EC-VSMC-signalling-on-a-chip consists of two parallel polydimethylsiloxane (PDMS) cell culture channels, separated by a flexible, porous PDMS membrane, mimicking the porosity of the internal elastic lamina. The hemodynamic EC-VSMC-signalling-on-a-chip allows co-culturing of human aortic endothelial cells (ECs) and human aortic vascular smooth muscle cells (VSMCs), separated by a porous membrane, which enables EC-VSMC interaction and signalling, crucial for the development and homeostasis of the vessel wall. The device allows real time cell imaging and control of hemodynamic conditions. The culture channels are surrounded on either side by vacuum channels to induce cyclic strain by applying cyclic suction, resulting in mechanical stretching and relaxation of the membrane in the cell culture channels. The blood flow is mimicked by creating a flow of medium at the EC side. Vascular cells remain viable during prolonged culturing, exhibit physiological morphology and organization and make cell-cell contact. During dynamic culturing of the device with a shear stress of 1-1.5 Pa and strain of 5-8%, VSMCs align perpendicular to the given strain in the direction of the flow and EC adopt a cobblestone morphology. To our knowledge, this is the first report on the development of a microfluidic device, which enables a co-culture of interacting ECs and VSMCs under hemodynamic conditions and presents a novel approach to systematically study the biological and mechanical components of the intimal-medial vascular unit.

The role of vitamin K in vascular calcification of patients with chronic kidney disease.

PubMed

Wuyts, Julie; Dhondt, Annemieke

2016-12-01

Patients with chronic kidney disease (CKD) are prone to vascular calcification. Pathogenetic mechanisms of vascular calcifications have been broadly studied and discussed such as the role of hyperphosphatemia, hypercalcemia, parathormone, and vitamin D. In recent years, new insights have been gained pointing to vitamin K as a main actor. It has been discovered that vitamin K is an essential cofactor for the activation of matrix Gla protein (MGP), a calcification inhibitor in the vessel wall. Patients with CKD often suffer from vitamin K deficiency, resulting in low active MGP and eventually a lack of inhibition of vascular calcification. Vitamin K supplementation and switching warfarin to new oral anticoagulants are potential treatments. In addition, MGP may have a role as a non-invasive biomarker for vascular calcification.

Transgene silencing of sucrose synthase in alfalfa stem vascular tissue by a truncated phosphoenolpyruvate carboxylase: sucrose synthase construct

USDA-ARS?s Scientific Manuscript database

An important role of sucrose synthase (SUS, EC 2.4.1.13) in plants is to provide UDP-glucose needed for cellulose synthesis in cell walls. We examined if over-expressing SUS in alfalfa (Medicago sativa L.) would increase cellulose content of stem cell walls. Alfalfa plants were transformed with two ...

Vascular defense responses in rice: peroxidase accumulation in xylem parenchyma cells and xylem wall thickening

NASA Technical Reports Server (NTRS)

Hilaire, E.; Young, S. A.; Willard, L. H.; McGee, J. D.; Sweat, T.; Chittoor, J. M.; Guikema, J. A.; Leach, J. E.

2001-01-01

The rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae is a vascular pathogen that elicits a defensive response through interaction with metabolically active rice cells. In leaves of 12-day-old rice seedlings, the exposed pit membrane separating the xylem lumen from the associated parenchyma cells allows contact with bacterial cells. During resistant responses, the xylem secondary walls thicken within 48 h and the pit diameter decreases, effectively reducing the area of pit membrane exposed for access by bacteria. In susceptible interactions and mock-inoculated controls, the xylem walls do not thicken within 48 h. Xylem secondary wall thickening is developmental and, in untreated 65-day-old rice plants, the size of the pit also is reduced. Activity and accumulation of a secreted cationic peroxidase, PO-C1, were previously shown to increase in xylem vessel walls and lumen. Peptide-specific antibodies and immunogold-labeling were used to demonstrate that PO-C1 is produced in the xylem parenchyma and secreted to the xylem lumen and walls. The timing of the accumulation is consistent with vessel secondary wall thickening. The PO-C1 gene is distinct but shares a high level of similarity with previously cloned pathogen-induced peroxidases in rice. PO-C1 gene expression was induced as early as 12 h during resistant interactions and peaked between 18 and 24 h after inoculation. Expression during susceptible interactions was lower than that observed in resistant interactions and was undetectable after infiltration with water, after mechanical wounding, or in mature leaves. These data are consistent with a role for vessel secondary wall thickening and peroxidase PO-C1 accumulation in the defense response in rice to X. oryzae pv. oryzae.

Redox-dependent impairment of vascular function in sickle cell disease.

PubMed

Aslan, Mutay; Freeman, Bruce A

2007-12-01

The vascular pathophysiology of sickle cell disease (SCD) is influenced by many factors, including adhesiveness of red and white blood cells to endothelium, increased coagulation, and homeostatic perturbation. The vascular endothelium is central to disease pathogenesis because it displays adhesion molecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall, and regulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances. The occurrence of intermittent vascular occlusion in SCD leads to reperfusion injury associated with granulocyte accumulation and enhanced production of reactive oxygen species. The participation of nitric oxide (NO) in oxidative reactions causes a reduction in NO bioavailability and contributes to vascular dysfunction in SCD. Therapeutic strategies designed to counteract endothelial, inflammatory, and oxidative abnormalities may reduce the frequency of hospitalization and blood transfusion, the incidence of pain, and the occurrence of acute chest syndrome and pulmonary hypertension in patients with SCD.

notch3 is essential for oligodendrocyte development and vascular integrity in zebrafish

PubMed Central

Zaucker, Andreas; Mercurio, Sara; Sternheim, Nitzan; Talbot, William S.; Marlow, Florence L.

2013-01-01

SUMMARY Mutations in the human NOTCH3 gene cause CADASIL syndrome (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). CADASIL is an inherited small vessel disease characterized by diverse clinical manifestations including vasculopathy, neurodegeneration and dementia. Here we report two mutations in the zebrafish notch3 gene, one identified in a previous screen for mutations with reduced expression of myelin basic protein (mbp) and another caused by a retroviral insertion. Reduced mbp expression in notch3 mutant embryos is associated with fewer oligodendrocyte precursor cells (OPCs). Despite an early neurogenic phenotype, mbp expression recovered at later developmental stages and some notch3 homozygous mutants survived to adulthood. These mutants, as well as adult zebrafish carrying both mutant alleles together, displayed a striking stress-associated accumulation of blood in the head and fins. Histological analysis of mutant vessels revealed vasculopathy, including: an enlargement (dilation) of vessels in the telencephalon and fin, disorganization of the normal stereotyped arrangement of vessels in the fin, and an apparent loss of arterial morphological structure. Expression of hey1, a well-known transcriptional target of Notch signaling, was greatly reduced in notch3 mutant fins, suggesting that Notch3 acts via a canonical Notch signaling pathway to promote normal vessel structure. Ultrastructural analysis confirmed the presence of dilated vessels in notch3 mutant fins and revealed that the vessel walls of presumed arteries showed signs of deterioration. Gaps in the arterial wall and the presence of blood cells outside of vessels in mutants indicated that compromised vessel structure led to hemorrhage. In notch3 heterozygotes, we found elevated expression of both notch3 itself and target genes, indicating that specific alterations in gene expression due to partial loss of Notch3 function might contribute to the abnormalities observed in heterozygous larvae and adults. Our analysis of zebrafish notch3 mutants indicates that Notch3 regulates OPC development and mbp gene expression in larvae, and maintains vascular integrity in adults. PMID:23720232

[Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

PubMed

Fischer, Tamás

2015-07-12

It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

PubMed

Schiffrin, Ernesto L

2015-12-04

This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

Expression of the high-affinity choline transporter CHT1 in rat and human arteries.

PubMed

Lips, Katrin S; Pfeil, Uwe; Reiners, Katja; Rimasch, Christoph; Kuchelmeister, Klaus; Braun-Dullaeus, Ruediger C; Haberberger, Rainer V; Schmidt, Rupert; Kummer, Wolfgang

2003-12-01

The arterial vascular wall contains a non-neuronal intrinsic cholinergic system. The rate-limiting step in acetylcholine (ACh) synthesis is choline uptake. A high-affinity choline transporter, CHT1, has recently been cloned from neural tissue and has been identified in epithelial cholinergic cells. Here we investigated its presence in rat and human arteries and in primary cell cultures of rat vascular cells (endothelial cells, smooth muscle cells, fibroblasts). CHT1-mRNA was detected in the arterial wall and in all isolated cell types by RT-PCR using five different CHT1-specific primer pairs. Antisera raised against amino acids 29-40 of the rat sequence labeled a single band (50 kD) in Western blots of rat aorta, and an additional higher molecular weight band appeared in the hippocampus. Immunohistochemistry demonstrated CHT1 immunoreactivity in endothelial and smooth muscle cells in situ and in all cultured cell types. A high-affinity [3H]-choline uptake mechanism sharing characteristics with neuronal high-affinity choline uptake, i.e., sensitivity to hemicholinium-3 and dependence on sodium, was demonstrated in rat thoracic aortic segments by microimager autoradiography. Expression of the high-affinity choline transporter CHT1 is a novel component of the intrinsic non-neuronal cholinergic system of the arterial vascular wall, predominantly in the intimal and medial layers.

Historical landmarks in vascular neurosurgery "On July 10th 2006, at the 70th Anniversary of the Department of Neurosurgery of Zürich Medical School".

PubMed

Hernesniemi, J; Dashti, R; Mateo, O; Cancela, P; Karatas, A; Niemelä, M

2008-01-01

Direct aneurysm surgery started more than 70 years ago. Introduction of cerebral angiography by Moniz in 20s and operating microscope by Yaşargil in 60s were the real cornerstones in vascular neurosurgery. Since then the development of neuroanestesiology and further development of non-invasive imaging (MRA and CTA) together with the latest development of operating microscopes with intraoperative ICG angio have shifted vascular microneurosurgery to a different level to still compete with the 'non-invasiness' of endovascular therapy. There is an increasing demand to perform the already forgotten bypasses mastered only by few and with the high-flow techniques (e.g. ELANA) we can treat lesions that some time ago were considered impossible. Endovascular embolization to reduce the flow in AVM before surgery is very helpful in those cases that can not be treated by embolization or radiosurgery alone. We still need to find a way to detect aneurysms before they rupture and especially those thin-walled that are in an increased risk of rupture. Recent data on the pathobiology of the aneurysm wall may help us to better understanding of the growth mechanisms and it might be possible to develop more potent local or systemic pharmaceutical therapy to induce myo-intimal hyperplasia occluding the aneurysm and strengthening the wall to prevent rupture.

Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity

NASA Technical Reports Server (NTRS)

Delp, M. D.; Colleran, P. N.; Wilkerson, M. K.; McCurdy, M. R.; Muller-Delp, J.

2000-01-01

Hindlimb unloading of rats results in a diminished ability of skeletal muscle arterioles to constrict in vitro and elevate vascular resistance in vivo. The purpose of the present study was to determine whether alterations in the mechanical environment (i.e., reduced fluid pressure and blood flow) of the vasculature in hindlimb skeletal muscles from 2-wk hindlimb-unloaded (HU) rats induces a structural remodeling of arterial microvessels that may account for these observations. Transverse cross sections were used to determine media cross-sectional area (CSA), wall thickness, outer perimeter, number of media nuclei, and vessel luminal diameter of feed arteries and first-order (1A) arterioles from soleus and the superficial portion of gastrocnemius muscles. Endothelium-dependent dilation (ACh) was also determined. Media CSA of resistance arteries was diminished by hindlimb unloading as a result of decreased media thickness (gastrocnemius muscle) or reduced vessel diameter (soleus muscle). ACh-induced dilation was diminished by 2 wk of hindlimb unloading in soleus 1A arterioles, but not in gastrocnemius 1A arterioles. These results indicate that structural remodeling and functional adaptations of the arterial microvasculature occur in skeletal muscles of the HU rat; the data suggest that these alterations may be induced by reductions in transmural pressure (gastrocnemius muscle) and wall shear stress (soleus muscle).

Contribution of vascular cell-derived cytokines to innate and inflammatory pathways in atherogenesis

PubMed Central

Loppnow, Harald; Buerke, Michael; Werdan, Karl; Rose-John, Stefan

2011-01-01

Abstract Inflammation is a central element of atherogenesis. Innate pathways contribute to vascular inflammation. However, the initial molecular process(es) starting atherogenesis remain elusive. The various risk factors, represented by particular compounds (activators), may cause altered cellular functions in the endothelium (e.g. vascular endothelial cell activation or -dysfunction), in invading cells (e.g. inflammatory mediator production) or in local vessel wall cells (e.g. inflammatory mediators, migration), thereby triggering the innate inflammatory process. The cellular components of innate immunology include granulocytes, natural killer cells and monocytes. Among the molecular innate constituents are innate molecules, such as the toll-like receptors or innate cytokines. Interleukin-1 (IL-1) and IL-6 are among the innate cytokines. Cytokines are potent activators of a great number of cellular functions relevant to maintain or commove homeostasis of the vessel wall. Within the vessel wall, vascular smooth muscle cells (SMCs) can significantly contribute to the cytokine-dependent inflammatory network by: (i) production of cytokines, (ii) response to cytokines and (iii) cytokine-mediated interaction with invading leucocytes. The cytokines IL-1 and IL-6 are involved in SMC-leucocyte interaction. The IL-6 effects are proposed to be mediated by trans-signalling. Dysregulated cellular functions resulting from dysregulated cytokine production may be the cause of cell accumulation, subsequent low-density lipoprotein accumulation and deposition of extracellular matrix (ECM). The deposition of ECM, increased accumulation of leucocytes and altered levels of inflammatory mediators may constitute an ‘innate-immunovascular-memory’ resulting in an ever-growing response to anew invasion. Thus, SMC-fostered inflammation, promoted by invading innate cells, may be a potent component for development and acceleration of atherosclerosis. PMID:21199323

Molecular control of wood formation in trees.

PubMed

Ye, Zheng-Hua; Zhong, Ruiqin

2015-07-01

Wood (also termed secondary xylem) is the most abundant biomass produced by plants, and is one of the most important sinks for atmospheric carbon dioxide. The development of wood begins with the differentiation of the lateral meristem, vascular cambium, into secondary xylem mother cells followed by cell expansion, secondary wall deposition, programmed cell death, and finally heartwood formation. Significant progress has been made in the past decade in uncovering the molecular players involved in various developmental stages of wood formation in tree species. Hormonal signalling has been shown to play critical roles in vascular cambium cell proliferation and a peptide-receptor-transcription factor regulatory mechanism similar to that controlling the activity of apical meristems is proposed to be involved in the maintenance of vascular cambium activity. It has been demonstrated that the differentiation of vascular cambium into xylem mother cells is regulated by plant hormones and HD-ZIP III transcription factors, and the coordinated activation of secondary wall biosynthesis genes during wood formation is mediated by a transcription network encompassing secondary wall NAC and MYB master switches and their downstream transcription factors. Most genes encoding the biosynthesis enzymes for wood components (cellulose, xylan, glucomannan, and lignin) have been identified in poplar and a number of them have been functionally characterized. With the availability of genome sequences of tree species from both gymnosperms and angiosperms, and the identification of a suite of wood-associated genes, it is expected that our understanding of the molecular control of wood formation in trees will be greatly accelerated. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

EMMPRIN (CD147/basigin) mediates platelet-monocyte interactions in vivo and augments monocyte recruitment to the vascular wall.

PubMed

Schulz, C; von Brühl, M-L; Barocke, V; Cullen, P; Mayer, K; Okrojek, R; Steinhart, A; Ahmad, Z; Kremmer, E; Nieswandt, B; Frampton, J; Massberg, S; Schmidt, R

2011-05-01

Platelets play a central role in hemostasis, in inflammatory diseases such as atherosclerosis, and during thrombus formation following vascular injury. Thereby, platelets interact intensively with monocytes and enhance their recruitment to the vascular wall. To investigate the role of the extracellular matrix metalloproteinase inducer (EMMPRIN) in platelet-monocyte interactions. Isolated human monocytes were perfused in vitro over firmly adherent platelets to allow investigation of the role of EMMPRIN in platelet-monocyte interactions under flow conditions. Monocytes readily bound to surface-adherent platelets. Both antibody blockade and gene silencing of monocyte EMMPRIN substantially attenuated firm adhesion of monocytes to platelets at arterial and venous shear rates. In vivo, platelet interactions with the murine monocyte cell line ANA-1 were significantly decreased when ANA-1 cells were pretreated with EMMPRIN-silencing small interfering RNA prior to injection into wild-type mice. Using intravital microscopy, we showed that recruitment of EMMPRIN-silenced ANA-1 to the injured carotid artery was significantly reduced as compared with control cells. Further silencing of EMMPRIN resulted in significantly fewer ANA-1-platelet aggregates in the mouse circulation as determined by flow cytometry. Finally, we identified glycoprotein (GP)VI as a critical corresponding receptor on platelets that mediates interaction with monocyte EMMPRIN. Thus, blocking of GPVI inhibited the effect of EMMPRIN on firm monocyte adhesion to platelets under arterial flow conditions in vitro, and abrogated EMMPRIN-mediated platelet-monocyte aggregate formation in vivo. EMMPRIN supports platelet-monocyte interactions and promotes monocyte recruitment to the arterial wall. Therefore, EMMPRIN might represent a novel target to reduce vascular inflammation and atherosclerotic lesion development. © 2011 International Society on Thrombosis and Haemostasis.

Biomimetic coating of cross-linked gelatin to improve mechanical and biological properties of electrospun PET: A promising approach for small caliber vascular graft applications.

PubMed

Pezzoli, Daniele; Cauli, Elisa; Chevallier, Pascale; Farè, Silvia; Mantovani, Diego

2017-09-01

Electrospun PET (ePET) is a promising material for small caliber vascular graft applications owing to its tunable mechanical properties, biocompatibility, and nanofibrous structure that mimic the morphology of natural extracellular matrix. However, the inherent inertness of PET impairs the adhesion and proliferation of endothelial cells on the inner surface of ePET tubular grafts, hindering the formation of a functional endothelium. Gelatin coatings, owing to their ability to promote endothelialization, are a valuable approach to overcome the limitations of ePET. Herein, a novel process for the deposition of stable biomimetic coatings of gelatin on ePET tubular grafts is proposed. Electrospun PET was first aminated by plasma treatment and then coated with a gelatin hydrogel cross-linked in situ by a Michael-type addition reaction. Amination provided a superhydrophilic behavior to the ePET surface, allowing easy gelatin interpenetration along the wall thickness of the tubular structure, and the obtainment of thin coatings that maintained the morphology of ePET fibers. Gelatin coating was stable at long term in a physiological-like environment, noncytotoxic and promoted in vitro cell adhesion and proliferation. Noteworthy, the mechanical properties of gelatin-coated ePET tubular grafts were improved in terms of elastic modulus, compliance, and elastic recoil, finally better matching the characteristics of native blood vessels. Altogether, the proposed coating technique successfully combines the advantages of ePET nanofibrous structure with cross-linked gelatin biological cues and mechanical reinforcement, and emerges as a promising strategy for the development of biocompatible small caliber vascular grafts with superior biomimetic and mechanical properties. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2405-2415, 2017. © 2017 Wiley Periodicals, Inc.

Topical hexylaminolevulinate and aminolevulinic acid photodynamic therapy: complete arteriole vasoconstriction occurs frequently and depends on protoporphyrin IX concentration in vessel wall.

PubMed

Middelburg, T A; de Bruijn, H S; Tettero, L; van der Ploeg van den Heuvel, A; Neumann, H A M; de Haas, E R M; Robinson, D J

2013-09-05

Vascular responses to photodynamic therapy (PDT) may influence the availability of oxygen during PDT and the extent of tumor destruction after PDT. However, for topical PDT vascular effects are largely unknown. Arteriole and venule diameters were measured before and after hexylaminolevulinate (HAL) and aminolevulinic acid (ALA) PDT and related to the protoporphyrin IX (PpIX) concentration in the vessel wall. A mouse skin fold chamber model and an intravital confocal microscope allowed direct imaging of the subcutaneous vessels underlying the treated area. In both HAL and ALA groups over 60% of arterioles constricted completely, while venules generally did not respond, except for two larger veins that constricted partially. Arteriole vasoconstriction strongly correlated with PpIX fluorescence intensity in the arteriole wall. Total PpIX fluorescence intensity was significantly higher for HAL than ALA for the whole area that was imaged but not for the arteriole walls. In conclusion, complete arteriole vasoconstriction occurs frequently in both HAL and ALA based topical PDT, especially when relatively high PpIX concentrations in arteriole walls are reached. Vasoconstriction will likely influence PDT effect and should be considered in studies on topical HAL and ALA-PDT. Also, our results may redefine the vasculature as a potential secondary target for topical PDT. Copyright © 2013 Elsevier B.V. All rights reserved.

Advances in helical stent design and fabrication thermal treatment and structural interaction studies of the simulated plaque-laden artery

NASA Astrophysics Data System (ADS)

Welch, Tre Raymond

Advancements in processing biomaterials have lead to the development of bioresorbable PLLA drug-loaded stents with different geometric configurations. To further advance the technology, systematic studies have been carried out. This dissertation consists of five specific aims: (1) To characterize the effects of thermal annealing on the mechanical characteristics of PLLA helical stent, (2) To characterize the mechanical characteristics of a PLLA double helix stent, (3) To characterize the physical and chemical properties of PLLA films impregnated with niacin and curcumin, (4) To characterize the mechanical interaction of expanded stent and vascular wall with both model simulation and experimental studies using PDMS phantom arteries, (5) To simulate the stent-plaque-artery interactions using computer models. Results and their significances in bioresorbable PLLA drug-loaded stents technology as well as clinical prospects will be presented. For Aim1, thermal annealing is shown to improve mechanical characteristics of the helical stent, including pressure-diameter response curves, incremental stiffness, and collapse pressure. Differential scanning calorimetric analysis of stent fiber reveals that thermal annealing contribute to increased percent crystallinity, thus enhanced mechanical characteristics of the stent. For Aim 2, the new double helix design was shown to leads to improved mechanical characteristics of stent, including pressure-diameter response curves, incremental stiffness, and collapse pressure. Further, it was found to lead to an increased percent crystallinity and reduced degradation rate. For Aim 3, the changes in mechanical properties, crystallinity in PLLA polymer loaded with curcumin, or niacin, or both from that of control are clearly delineated. Results from Aim 4 shed lights on the mechanical disturbance in the vicinity of deployed stent and vascular wall as well as the abnormal shear stresses on the vascular endothelium. Their implications in triggering thrombi formation are discussed. Results from Aim 5 provided insights on the stent-plaque-artery mechanical interaction and how the altered mechanical environment after stent deployment could affect vascular remodeling and factors lead to re-stenosis. The significances of this work in advancing the bioresorbable PLLA drug-loaded stents technology as well as its clinical prospects are presented.

From structure to function - a family portrait of plant subtilases.

PubMed

Schaller, Andreas; Stintzi, Annick; Rivas, Susana; Serrano, Irene; Chichkova, Nina V; Vartapetian, Andrey B; Martínez, Dana; Guiamét, Juan J; Sueldo, Daniela J; van der Hoorn, Renier A L; Ramírez, Vicente; Vera, Pablo

2018-05-01

Contents Summary 901 I. Introduction 901 II. Biochemistry and structure of plant SBTs 902 III. Phylogeny of plant SBTs and family organization 903 IV. Physiological roles of plant SBTs 905 V. Conclusions and outlook 911 Acknowledgements 912 References 912 SUMMARY: Subtilases (SBTs) are serine peptidases that are found in all three domains of life. As compared with homologs in other Eucarya, plant SBTs are more closely related to archaeal and bacterial SBTs, with which they share many biochemical and structural features. However, in the course of evolution, functional diversification led to the acquisition of novel, plant-specific functions, resulting in the present-day complexity of the plant SBT family. SBTs are much more numerous in plants than in any other organism, and include enzymes involved in general proteolysis as well as highly specific processing proteases. Most SBTs are targeted to the cell wall, where they contribute to the control of growth and development by regulating the properties of the cell wall and the activity of extracellular signaling molecules. Plant SBTs affect all stages of the life cycle as they contribute to embryogenesis, seed development and germination, cuticle formation and epidermal patterning, vascular development, programmed cell death, organ abscission, senescence, and plant responses to their biotic and abiotic environments. In this article we provide a comprehensive picture of SBT structure and function in plants. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

The mechanical properties of infrainguinal vascular bypass grafts: their role in influencing patency.

PubMed

Sarkar, S; Salacinski, H J; Hamilton, G; Seifalian, A M

2006-06-01

When autologous vein is unavailable, prosthetic graft materials, particularly expanded polytetrafluoroethylene are used for peripheral arterial revascularisation. Poor long term patency of prosthetic materials is due to distal anastomotic intimal hyperplasia. Intimal hyperplasia is directly linked to shear stress abnormalities at the vessel wall. Compliance and calibre mismatch between native vessel and graft, as well as anastomotic line stress concentration contribute towards unnatural wall shear stress. High porosity reduces graft compliance by causing fibrovascular infiltration, whereas low porosity discourages the development of an endothelial lining and hence effective antithrombogenicity. Therefore, consideration of mechanical properties is necessary in graft development. Current research into synthetic vascular grafts concentrates on simulating the mechanical properties of native arteries and tissue engineering aims to construct a new biological arterial conduit.

Defining the Diverse Cell Populations Contributing to Lignification in Arabidopsis Stems.

PubMed

Smith, Rebecca A; Schuetz, Mathias; Karlen, Steven D; Bird, David; Tokunaga, Naohito; Sato, Yasushi; Mansfield, Shawn D; Ralph, John; Samuels, A Lacey

2017-06-01

Many land plants evolved tall and sturdy growth habits due to specialized cells with thick lignified cell walls: tracheary elements that function in water transport and fibers that function in structural support. The objective of this study was to define how and when diverse cell populations contribute lignin precursors, monolignols, to secondary cell walls during lignification of the Arabidopsis ( Arabidopsis thaliana ) inflorescence stem. Previous work demonstrated that, when lignin biosynthesis is suppressed in fiber and tracheary element cells with thickened walls, fibers become lignin-depleted while vascular bundles still lignify, suggesting that nonlignifying neighboring xylem cells are contributing to lignification. In this work, we dissect the contributions of different cell types, specifically xylary parenchyma and fiber cells, to lignification of the stem using cell-type-specific promoters to either knock down an essential monolignol biosynthetic gene or to introduce novel monolignol conjugates. Analysis of either reductions in lignin in knockdown lines, or the addition of novel monolignol conjugates, directly identifies the xylary parenchyma and fiber cell populations that contribute to the stem lignification and the developmental timing at which each contribution is most important. © 2017 American Society of Plant Biologists. All Rights Reserved.

Noninvasive assessment of arterial function in children: clinical applications

PubMed Central

Aggoun, Y; Beghetti, M

2002-01-01

Non invasive methods to assess arterial function are widely used in adults. The development and progression of arterial vascular disease is a multifactorial process that can start early in life, thus even in a pediatric population. Risk factors for cardiovascular disease mediate their effects by altering the structure, properties and function of wall and endothelial components of the arterial blood vessels. The ability to detect and monitor sub-clinical damage, representing the cumulative and integrated influence of risk factors in impairing arterial wall integrity, holds potential to further refine cardiovascular risk stratification and enable early intervention to prevent or attenuate disease progression. Measurements that provide more direct information in relation to changes in arterial wall integrity clearly hold predictive and therapeutic potential. The aim of this current review will be to describe the non-invasive procedure used in children to investigate the mechanical properties of a great elastic artery, the common carotid, and the endothelial function of the brachial artery. The accuracy of recording noninvasively the blood pressure wave contour along the arterial tree has been improved by the technique of applanation tonometry. The results obtained with these methods in previous studies are described. PMID:22368620

Mechanical design in arteries.

PubMed

Shadwick, R E

1999-12-01

The most important mechanical property of the artery wall is its non-linear elasticity. Over the last century, this has been well-documented in vessels in many animals, from humans to lobsters. Arteries must be distensible to provide capacitance and pulse-smoothing in the circulation, but they must also be stable to inflation over a range of pressure. These mechanical requirements are met by strain-dependent increases in the elastic modulus of the vascular wall, manifest by a J-shaped stress-strain curve, as typically exhibited by other soft biological tissues. All vertebrates and invertebrates with closed circulatory systems have arteries with this non-linear behaviour, but specific tissue properties vary to give correct function for the physiological pressure range of each species. In all cases, the non-linear elasticity is a product of the parallel arrangement of rubbery and stiff connective tissue elements in the artery wall, and differences in composition and tissue architecture can account for the observed variations in mechanical properties. This phenomenon is most pronounced in large whales, in which very high compliance in the aortic arch and exceptionally low compliance in the descending aorta occur, and is correlated with specific modifications in the arterial structure.

3D-Printed Tissue-Mimicking Phantoms for Medical Imaging and Computational Validation Applications

PubMed Central

Shahmirzadi, Danial; Li, Ronny X.; Doyle, Barry J.; Konofagou, Elisa E.; McGloughlin, Tim M.

2014-01-01

Abstract Abdominal aortic aneurysm (AAA) is a permanent, irreversible dilation of the distal region of the aorta. Recent efforts have focused on improved AAA screening and biomechanics-based failure prediction. Idealized and patient-specific AAA phantoms are often employed to validate numerical models and imaging modalities. To produce such phantoms, the investment casting process is frequently used, reconstructing the 3D vessel geometry from computed tomography patient scans. In this study the alternative use of 3D printing to produce phantoms is investigated. The mechanical properties of flexible 3D-printed materials are benchmarked against proven elastomers. We demonstrate the utility of this process with particular application to the emerging imaging modality of ultrasound-based pulse wave imaging, a noninvasive diagnostic methodology being developed to obtain regional vascular wall stiffness properties, differentiating normal and pathologic tissue in vivo. Phantom wall displacements under pulsatile loading conditions were observed, showing good correlation to fluid–structure interaction simulations and regions of peak wall stress predicted by finite element analysis. 3D-printed phantoms show a strong potential to improve medical imaging and computational analysis, potentially helping bridge the gap between experimental and clinical diagnostic tools. PMID:28804733

mPGES-1 (Microsomal Prostaglandin E Synthase-1) Mediates Vascular Dysfunction in Hypertension Through Oxidative Stress.

PubMed

Avendaño, María S; García-Redondo, Ana B; Zalba, Guillermo; González-Amor, María; Aguado, Andrea; Martínez-Revelles, Sonia; Beltrán, Luis M; Camacho, Mercedes; Cachofeiro, Victoria; Alonso, María J; Salaices, Mercedes; Briones, Ana M

2018-06-11

mPGES-1 (microsomal prostaglandin E synthase-1), the downstream enzyme responsible for PGE 2 (prostaglandin E 2 ) synthesis in inflammatory conditions and oxidative stress are increased in vessels from hypertensive animals. We evaluated the role of mPGES-1-derived PGE 2 in the vascular dysfunction and remodeling in hypertension and the possible contribution of oxidative stress. We used human peripheral blood mononuclear cells from asymptomatic patients, arteries from untreated and Ang II (angiotensin II)-infused mPGES-1 -/- and mPGES-1 +/+ mice, and vascular smooth muscle cells exposed to PGE 2 In human cells, we found a positive correlation between mPGES-1 mRNA and carotid intima-media thickness ( r =0.637; P <0.001) and with NADPH oxidase-dependent superoxide production ( r =0.417; P <0.001). In Ang II-infused mice, mPGES-1 deletion prevented all of the following: (1) the augmented wall:lumen ratio, vascular stiffness, and altered elastin structure; (2) the increased gene expression of profibrotic and proinflammatory markers; (3) the increased vasoconstrictor responses and endothelial dysfunction; (4) the increased NADPH oxidase activity and the diminished mitochondrial membrane potential; and (5) the increased reactive oxygen species generation and reduced NO bioavailability. In vascular smooth muscle cells or aortic segments, PGE 2 increased NADPH oxidase expression and activity and reduced mitochondrial membrane potential, effects that were abolished by antagonists of the PGE 2 receptors (EP), EP1 and EP3, and by JNK (c-Jun N-terminal kinase) and ERK1/2 (extracellular-signal-regulated kinases 1/2) inhibition. Deletion of mPGES-1 augmented vascular production of PGI 2 suggesting rediversion of the accumulated PGH 2 substrate. In conclusion, mPGES-1-derived PGE 2 is involved in vascular remodeling, stiffness, and endothelial dysfunction in hypertension likely through an increase of oxidative stress produced by NADPH oxidase and mitochondria. © 2018 American Heart Association, Inc.

[Role of C5b-9 expression in skeletal muscle blood vessels in necrotizing myopathy].

PubMed

Cong, Lu; Pu, Chuanqiang; Mao, Yanling; Liu, Jiexiao; Lu, Xianghui; Wang, Qian

2012-05-01

To investigate the expression of C5b-9 in the skeletal muscle blood vessels in patients with necrotizing myopathy and explore its role in the pathogenesis of this disease. The expression of C5b-9 and MHC-I in the skeletal muscular fibers and blood vessels in 4 patients with necrotizing myopathy was detected using enzymohistochemistry and immunohistochemistry. Focal or dispersive necrotic muscle fibers with obvious phagocytosis were observed in all the 4 patients. No inflammatory cell infiltration was found in the perimysium or perivascular regions. HE staining showed a decreased number of local small blood vessels, and the some small blood vessels showed thickened vascular walls. Immunohistochemistry detected prominent C5b-9 expression in the necrotic muscle fibers and the blood vessels, and diffuse strong C5b-9 expression was found in the vascular walls, vascular endothelial cells and the smooth muscle layer. No MHC-I deposition was detected in the muscular fibers and blood vessels. C5b-9 contributes to the pathogenesis of necrotizing myopathy mediated by pathologies in the blood vessels.

Patent ductus arteriosus in mice with smooth muscle-specific Jag1 deletion

PubMed Central

Feng, Xuesong; Krebs, Luke T.; Gridley, Thomas

2010-01-01

The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus and is one of the most common congenital heart defects. Mice with smooth muscle cell-specific deletion of Jag1, which encodes a Notch ligand, die postnatally from patent ductus arteriosus. These mice exhibit defects in contractile smooth muscle cell differentiation in the vascular wall of the ductus arteriosus and adjacent descending aorta. These defects arise through an inability to propagate the JAG1-Notch signal via lateral induction throughout the width of the vascular wall. Both heterotypic endothelial smooth muscle cell interactions and homotypic vascular smooth muscle cell interactions are required for normal patterning and differentiation of the ductus arteriosus and adjacent descending aorta. This new model for a common congenital heart defect provides novel insights into the genetic programs that underlie ductus arteriosus development and closure. PMID:21068062

Blood-Vessel Mimicking Structures by Stereolithographic Fabrication of Small Porous Tubes Using Cytocompatible Polyacrylate Elastomers, Biofunctionalization and Endothelialization

PubMed Central

Huber, Birgit; Engelhardt, Sascha; Meyer, Wolfdietrich; Krüger, Hartmut; Wenz, Annika; Schönhaar, Veronika; Tovar, Günter E. M.; Kluger, Petra J.; Borchers, Kirsten

2016-01-01

Blood vessel reconstruction is still an elusive goal for the development of in vitro models as well as artificial vascular grafts. In this study, we used a novel photo-curable cytocompatible polyacrylate material (PA) for freeform generation of synthetic vessels. We applied stereolithography for the fabrication of arbitrary 3D tubular structures with total dimensions in the centimeter range, 300 µm wall thickness, inner diameters of 1 to 2 mm and defined pores with a constant diameter of approximately 100 µm or 200 µm. We established a rinsing protocol to remove remaining cytotoxic substances from the photo-cured PA and applied thio-modified heparin and RGDC-peptides to functionalize the PA surface for enhanced endothelial cell adhesion. A rotating seeding procedure was introduced to ensure homogenous endothelial monolayer formation at the inner luminal tube wall. We showed that endothelial cells stayed viable and adherent and aligned along the medium flow under fluid-flow conditions comparable to native capillaries. The combined technology approach comprising of freeform additive manufacturing (AM), biomimetic design, cytocompatible materials which are applicable to AM, and biofunctionalization of AM constructs has been introduced as BioRap® technology by the authors. PMID:27104576

Inertial particle dynamics in large artery flows - Implications for modeling arterial embolisms.

PubMed

Mukherjee, Debanjan; Shadden, Shawn C

2017-02-08

The complexity of inertial particle dynamics through swirling chaotic flow structures characteristic of pulsatile large-artery hemodynamics renders significant challenges in predictive understanding of transport of such particles. This is specifically crucial for arterial embolisms, where knowledge of embolus transport to major vascular beds helps in disease diagnosis and surgical planning. Using a computational framework built upon image-based CFD and discrete particle dynamics modeling, a multi-parameter sampling-based study was conducted on embolic particle dynamics and transport. The results highlighted the strong influence of material properties, embolus size, release instance, and embolus source on embolus distribution to the cerebral, renal and mesenteric, and ilio-femoral vasculature beds. The study also isolated the importance of shear-gradient lift, and elastohydrodynamic contact, in affecting embolic particle transport. Near-wall particle re-suspension due to lift alters aortogenic embolic particle dynamics significantly as compared to cardiogenic. The observations collectively indicated the complex interplay of particle inertia, fluid-particle density ratio, and wall collisions, with chaotic flow structures, which render the overall motion of the particles to be non-trivially dispersive in nature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hemodynamics

PubMed Central

Secomb, Timothy W.

2016-01-01

A review is presented of the physical principles governing the distribution of blood flow and blood pressure in the vascular system. The main factors involved are the pulsatile driving pressure generated by the heart, the flow characteristics of blood, and the geometric structure and mechanical properties of the vessels. The relationship between driving pressure and flow in a given vessel can be understood by considering the viscous and inertial forces acting on the blood. Depending on the vessel diameter and other physical parameters, a wide variety of flow phenomena can occur. In large arteries, the propagation of the pressure pulse depends on the elastic properties of the artery walls. In the microcirculation, the fact that blood is a suspension of cells strongly influences its flow properties and leads to a non-uniform distribution of hematocrit among microvessels. The forces acting on vessel walls include shear stress resulting from blood flow and circumferential stress resulting from blood pressure. Biological responses to these forces are important in the control of blood flow and the structural remodeling of vessels, and also play a role in major disease processes including hypertension and atherosclerosis. Consideration of hemodynamics is essential for a comprehensive understanding of the functioning of the circulatory system. PMID:27065172

Pulmonary vascular disease in a rabbit a high altitude

NASA Astrophysics Data System (ADS)

Heath, Donald; Williams, David; Rios-Datenz, Jaime; Gosney, John

1990-03-01

A male weanling rabbit of the New Zealand White strain, born and living at an altitude of 3800 m in La Paz, Bolivia, developed right ventricular hypertrophy. This was found to be associated with growth of vascular smooth muscle cells in the intima of pulmonary arterioles, and contrasted with muscularization of the walls of pulmonary arterioles, without extension into the intima, found in a healthy, high-altitude control rabbit of the same strain. A low-altitude control showed no such muscularization. It is concluded that alveolar hypoxia, acting directly or through an intermediate agent, is a growth factor for vascular smooth muscle cells in pulmonary arterioles. This is the first report of pulmonary vascular disease due to high altitude in rabbits.

Hepatic overexpression of the prodomain of furin lessens progression of atherosclerosis and reduces vascular remodeling in response to injury.

PubMed

Lei, Xia; Basu, Debapriya; Li, Zhiqiang; Zhang, Maoxiang; Rudic, R Dan; Jiang, Xian-Cheng; Jin, Weijun

2014-09-01

Atherosclerosis is a complex disease, involving elevated LDL-c, lipid accumulation in the blood vessel wall, foam cell formation and vascular dysfunction. Lowering plasma LDL-c is the cornerstone of current management of cardiovascular disease. However, new approaches which reduce plasma LDL-c and lessen the pathological vascular remodeling occurring in the disease should also have therapeutic value. Previously, we found that overexpression of profurin, the 83-amino acid prodomain of the proprotein convertase furin, lowered plasma HDL levels in wild-type mice. The question that remained was whether it had effects on apolipoprotein B (ApoB)-containing lipoproteins. Adenovirus mediated overexpression of hepatic profurin in Ldlr(-/-)mice and wild-type mice were used to evaluate effects of profurin on ApoB-containing lipoproteins, atherosclerosis and vascular remodeling. Hepatic profurin overexpression resulted in a significant reduction in atherosclerotic lesion development in Ldlr(-/-)mice and a robust reduction in plasma LDL-c. Metabolic studies revealed lower secretion of ApoB and triglycerides in VLDL particles. Mechanistic studies showed that in the presence of profurin, hepatic ApoB, mainly ApoB100, was degraded by proteasomes. There was no effect on ApoB mRNA expression. Importantly, short-term hepatic profurin overexpression did not result in hepatic lipid accumulation. Blood vessel wall thickening caused by either wire-induced femoral artery injury or common carotid artery ligation was reduced. Profurin expression inhibited proliferation and migration in vascular smooth muscle cells in vitro. These results indicate that a profurin-based therapy has the potential to treat atherosclerosis by improving metabolic lipid profiles and reducing both atherosclerotic lesion development and pathological vascular remodeling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

PubMed Central

Chiu, Jeng-Jiann; Chien, Shu

2013-01-01

Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions. PMID:21248169

45 CFR 675.3 - Medical clearance criteria.

Code of Federal Regulations, 2010 CFR

2010-10-01

... following major organ systems: (1) Lungs and chest wall. (2) Heart and vascular system. (3) Abdominal organs...) Musculoskeletal. (7) Skin and cellular tissues. (8) Neurological Disorders. (9) Psychiatric or psychological. (10...

Experimental study of laminar blood flow through an artery treated by a stent implantation: characterisation of intra-stent wall shear stress.

PubMed

Benard, Nicolas; Coisne, Damien; Donal, Erwan; Perrault, Robert

2003-07-01

The stimulation of endothelial cells by arterial wall shear stress (WSS) plays a central role in restenosis. The fluid-structure interaction between stent wire and blood flow alters the WSS, particularly between stent struts. We have designed an in vitro model of struts of an intra-vascular prosthesis to study blood flow through a 'stented' section. The experimental artery consisted of a transparent square section test vein, which reproduced the strut design (100x magnifying power). A programmable pump was used to maintain a steady blood flow. Particle image velocimetry method was used to measure the flow between and over the stent branches, and to quantify WSS. Several prosthesis patterns that were representative of the total stent strut geometry were studied in a greater detail. We obtained WSS values of between -1.5 and 1.5Pa in a weak SS area which provided a source of endothelial stimulation propitious to restenosis. We also compared two similar patterns located in two different flow areas (one at the entry of the stent and one further downstream). We only detected a slight difference between the weakest SS levels at these two sites. As the endothelial proliferation is greatly influenced by the SS, knowledge of the SS modification induced by the stent implantation could be of importance for intra-vascular prostheses design optimisation and thus can help to reduce the restenosis incidence rate.

Mechanisms of desiccation tolerance in the bromeliad Pitcairnia burchellii Mez: biochemical adjustments and structural changes.

PubMed

Vieira, Evandro Alves; Silva, Kleber Resende; Oriani, Aline; Moro, Camila Fernandes; Braga, Marcia Regina

2017-12-01

Rocky outcrops represent the diversity center of vascular desiccation tolerant (DT) plants. Vegetation in this environment is exposed to an extended dry season and extreme conditions due to rocky soils and high sun exposure. In this study, we demonstrated that Pitcairnia burchellii, a bromeliad from rocky outcrops, tolerates intense desiccation for about 90 days due to strategies as accumulation of compatible osmolytes and antioxidant substances together with leaf morphological changes. In dehydrated plants, an increase in antioxidant activity was observed and the vacuolization of parenchyma cells was accompanied by proline accumulation in leaves and rhizomes. Precursors related to phenylpropanoid pathway increased significantly during plant dehydration. Accordingly, increases in anthocyanin and phenolic contents as well as lignin deposition were observed in leaves of dehydrated plants. Cell divisions and a decrease in stored starch were observed in the rhizomes indicating starch mobilization. Anatomical analyses revealed the presence of a more developed water-storage tissue in dehydrated leaves. During desiccation, leaves curl upwards and the adaxial V deep water-storage tissue is supported by two larger lateral vascular bundles. Cell wall folding and an increased proportion of arabinose-containing polymers was observed in leaves under dehydration, suggesting increasing of cell wall flexibility during desiccation. Such biochemical and morphological changes are consistent with the ability of P. burchellii to tolerate intense desiccation and behave as a resurrection species. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cerebrovasculoprotective Effects of Azilsartan Medoxomil in Diabetes

PubMed Central

Abdelsaid, Mohammed; Coucha, Maha; Ergul, Adviye

2014-01-01

We have shown that Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes, develop significant cerebrovascular remodeling by 18 weeks of age, which is characterized by increased media thickness and matrix deposition. While early glycemic control prevents diabetes-mediated remodeling of the cerebrovasculature, whether the remodeling can be reversed is unknown. Given that angiotensin II Type 1 receptor blockers (ARBs) reverse pathological vascular remodeling and function independent of changes in blood pressure in other vascular beds, we hypothesized that azilsartan medoxomil, a new ARB, is vasculoprotective by preventing and reversing cerebrovascular remodeling in diabetes. Control Wistar and diabetic GK rats (n=6–8/group), were treated with vehicle (water) or azilsartan medoxomil (3 mg/kg/day) from 14 to 18 or 18 to 22 weeks of age before or after vascular remodeling is established, respectively. Blood glucose and blood pressure were monitored and middle cerebral artery structure and function were evaluated using pressurized arteriography. Blood glucose was higher in GK rats compared to Wistar rats. Azilsartan treatment lowered blood glucose in diabetes with no effect on blood pressure. Diabetic animals exhibited lower myogenic tone, increased wall thickness, and cross sectional area compared to controls, which were corrected by azilsartan treatment when started at the onset of diabetes or later after vascular remodeling is established. Azilsartan medoxomil offers preventive and therapeutic vasculoprotection in diabetes-induced cerebrovascular remodeling and myogenic dysfunction and this is independent of blood pressure. PMID:24999268

Improvement of photodynamic activity of aluminium sulphophthalocyanine due to biotinylation

NASA Astrophysics Data System (ADS)

Meerovich, Irina G.; Jerdeva, Victoria V.; Derkacheva, Valentina M.; Meerovich, Gennadii A.; Lukyanets, Eugeny A.; Kogan, Eugenia A.; Savitsky, Alexander P.

2003-09-01

The photodynamic activity of dibiotinylated aluminium sulphophthalocyanine in vitro and in vivo were studied. It was obtained that in vitro dibiotinylated aluminium sulphophthalocyanine provides the effective damage of small cell lung carcinoma OAT-75. In vivo dibiotinylated aluminium sulphophthalocyanine causes destruction of tumor (Erlich carcinoma), results in total necrosis of tumor tissue and expresses vascular damage (trombosis and destruction of vascular walls) even in concentration 0.25 mg/kg of a body weight.

Structural and functional changes of carotid wall properties in patients with acromegaly are not restored after 1 year of GH/IGF1 normalization.

PubMed

Găloiu, S; Jurcuţ, R; Vlădaia, A; Florian, A; Purice, M; Popescu, B A; Ginghină, C; Coculescu, M

2012-04-01

Vascular changes are common in acromegaly (ACM). Current therapies can normalise the levels of both growth hormone (GH) and insulin-like growth factor (IGF1). To establish whether the ACM vascular changes in patients with effectively managed disease are different from those in patients with an active condition. 64 ACM patients were tested for serum GH (random and during an oral glucose tolerance test) and IGF1. Ultrasonography of the right common carotid (RCC) explored structural (the carotid diameter and intima-media thickness index (IMT)) and functional (the augmentation index (AIx), elastic modulus (Ep), and local pulse wave velocity (PWV)) arterial parameters in the ACM patients (groups A and B) and an age- and sex-matched control group of 21 patients without acromegaly (group C). The ACM patients were divided into 2 subgroups that had similar cardiovascular risk factor profiles: A (n=10, with controlled ACM), and B (n=54, with active ACM). The AIx was higher in groups A (27.7% [2.2-54.3]) and B (20.0% [ - 38.2-97.1]) than in group C (3.5% [ - 11.3-31.1]), p=0.01 and 0.002, respectively. The group B patients presented with poorer functional carotid wall parameters than the control subjects: Ep-95.5 [33-280] KPa vs. 77.5 [39-146] KPa, p=0.01; and PWV-6 [3.6-10.4] m/s vs. 5.4 [3.9-7.2] m/s, p=0.03.The ACM patients had greater RCC diameters (6.4 ± 0.6 mm vs. 5.7 ± 0.6 mm, p<0.001) and IMT values (0.72 ± 0.13 mm vs. 0.58 ± 0.08 mm, p<0.001) than the subjects in group C. Both the controlled and active ACM patients showed structural arterial changes. After 1 year of disease control, the patients with controlled ACM showed improvements in the functional, but not the structural, arterial parameters compared with the patients with an active condition. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Duinen, S.G.; Castano, E.M.; Prelli, F.

1987-08-01

Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related ..beta..-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from themore » leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approx. 4000 and its partial amino acid sequence to position 21 showed homology to the ..beta..-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of ..beta..-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.« less

TGF-β1 in Vascular Wall Pathology: Unraveling Chronic Venous Insufficiency Pathophysiology.

PubMed

Serralheiro, Pedro; Soares, Andreia; Costa Almeida, Carlos M; Verde, Ignacio

2017-11-26

Chronic venous insufficiency and varicose veins occur commonly in affluent countries and are a socioeconomic burden. However, there remains a relative lack of knowledge about venous pathophysiology. Various theories have been suggested, yet the molecular sequence of events is poorly understood. Transforming growth factor-beta one (TGF-β1) is a highly complex polypeptide with multifunctional properties that has an active role during embryonic development, in adult organ physiology and in the pathophysiology of major diseases, including cancer and various autoimmune, fibrotic and cardiovascular diseases. Therefore, an emphasis on understanding its signaling pathways (and possible disruptions) will be an essential requirement for a better comprehension and management of specific diseases. This review aims at shedding more light on venous pathophysiology by describing the TGF-β1 structure, function, activation and signaling, and providing an overview of how this growth factor and disturbances in its signaling pathway may contribute to specific pathological processes concerning the vessel wall which, in turn, may have a role in chronic venous insufficiency.

Left coronary aneurysmal dilation and subaortic stenosis in a dog.

PubMed

Hernandez, Juan L; Bélanger, Marie-Claude; Benoit-Biancamano, Marie-Odile; Girard, Christiane; Pibarot, Philippe

2008-06-01

A 6-month-old German shepherd dog was referred for evaluation of a cardiac murmur. Upon physical examination, the auscultated heart rate was 120 beats/min, and a grade IV/VI systolic heart murmur with a point of maximal intensity over the left heart base radiating up the neck was heard. The standard echocardiographic examination showed subaortic stenosis and an anechoic tubular structure extending from the sinus of Valsalva to the left ventricular posterior wall. Aneurysmal left coronary artery (CA) was confirmed by angiography. The dog was euthanized and post-mortem examination showed severe dilatation of the proximal left CA and confirmed the subaortic stenosis. Histopathology did not demonstrate abnormalities in the walls of the CA, aorta or pulmonary artery. The exact cause of the CA aneurysmal dilation remains unknown. Subaortic stenosis, elevated coronary vascular resistance or a congenital anomaly may have contributed to the dilation. To our knowledge, coronary aneurysmal dilation has never been described in dogs. Standard echocardiography provides reliable information on coronary anatomy.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.

PubMed

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-10-24

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

PubMed Central

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-01-01

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic. PMID:27783043

Brittle stalk 2 encodes a putative glycosylphosphatidylinositol-anchored protein that affects mechanical strength of maize tissues by altering the composition and structure of secondary cell walls.

PubMed

Ching, Ada; Dhugga, Kanwarpal S; Appenzeller, Laura; Meeley, Robert; Bourett, Timothy M; Howard, Richard J; Rafalski, Antoni

2006-10-01

A spontaneous maize mutant, brittle stalk-2 (bk2-ref), exhibits dramatically reduced tissue mechanical strength. Reduction in mechanical strength in the stalk tissue was highly correlated with a reduction in the amount of cellulose and an uneven deposition of secondary cell wall material in the subepidermal and perivascular sclerenchyma fibers. Cell wall accounted for two-thirds of the observed reduction in dry matter content per unit length of the mutant stalk in comparison to the wildtype stalk. Although the cell wall composition was significantly altered in the mutant in comparison to the wildtype stalks, no compensation by lignin and cell wall matrix for reduced cellulose amount was observed. We demonstrate that Bk2 encodes a Cobra-like protein that is homologous to the rice Bc1 protein. In the bk2-ref gene, a 1 kb transposon-like element is inserted in the beginning of the second exon, disrupting the open reading frame. The Bk2 gene was expressed in the stalk, husk, root, and leaf tissues, but not in the embryo, endosperm, pollen, silk, or other tissues with comparatively few or no secondary cell wall containing cells. The highest expression was in the isolated vascular bundles. In agreement with its role in secondary wall formation, the expression pattern of the Bk2 gene was very similar to that of the ZmCesA10, ZmCesA11, and ZmCesA12 genes, which are known to be involved in secondary wall formation. We have isolated an independent Mutator-tagged allele of bk2, referred to as bk2-Mu7, the phenotype of which is similar to that of the spontaneous mutant. Our results demonstrate that mutations in the Bk2 gene affect stalk strength in maize by interfering with the deposition of cellulose in the secondary cell wall in fiber cells.

Experimental research on preventing mechanical phlebitis arising from indwelling needles in intravenous therapy by external application of mirabilite

PubMed Central

Lu, Yanyan; Hao, Chunyan; He, Wubin; Tang, Can; Shao, Zhenya

2018-01-01

Various types of complications arising from intravenous indwelling needles have become a challenge in clinical care. It is urgent to seek a simple and cost-effective method for prevention and treatment of phlebitis. We investigated the roles of mirabilite in preventing and treating phlebitis caused by intravenous indwelling needles and provide guidance for prevention and treatment of mechanical phlebitis caused by intravenous indwelling needles. A total of 57 healthy congeneric big-eared New Zealand rabbits were randomly divided into 3 groups: blank control, indwelling needle, and group with external application of mirabilite. The ear vein of each rabbit was punctured with an intravenous indwelling needle. The ear vein specimens were taken at 3, 5, and 7 days after indwelling. The hematoxylin and eosin stained pathological tissue sections of the ear veins of the rabbits in each group were observed. The expression levels of IL-1 and IL-6, and tumour necrosis factor-α (TNF-α) in the vascular tissue of the ear veins of the rabbits in each group were detected with the immunofluorescence method. In the blank control group, there was no inflammatory cellular infiltration and no proliferation of fibrous tissue around the vascular wall. With the increase of the indwelling time, proliferation of fibrous tissue in vascular wall, increased inflammatory cellular infiltration and organized thrombus in the vascular tissue occurred in the ear veins of the rabbits in the indwelling needle group and group with external application of mirabilite. Compared with the indwelling needle group, the group with external application of mirabilite had significantly decreased fibrous tissue in the vascular wall and significantly decreased inflammatory cellular infiltration. At the same point in indwelling time, the expression levels of IL-1, IL-6, and TNF-α in the indwelling needle and group with external application of mirabilite were significantly higher than that in the blank control group (P<0.05). The expression levels of IL-1, IL-6, and TNF-α in the group with external application of mirabilite were lower than that in the indwelling needle group (P<0.05). The expression levels of IL-1, IL-6, and TNF-α are positively correlated with the indwelling time within the same group at different points in time. In conclusion, external application of mirabilite can significantly decrease infiltration of venous inflammatory cells of the rabbit ear margin, proliferation of fibrous tissue and thrombosis in the vascular wall, significant decrease the expression levels of IL-1, IL-6, and TNF-α in the mechanical phlebitis caused by intravenous indwelling needles, and decrease the inflammatory responses of the ear veins of rabbits. PMID:29250150

Experimental research on preventing mechanical phlebitis arising from indwelling needles in intravenous therapy by external application of mirabilite.

PubMed

Lu, Yanyan; Hao, Chunyan; He, Wubin; Tang, Can; Shao, Zhenya

2018-01-01

Various types of complications arising from intravenous indwelling needles have become a challenge in clinical care. It is urgent to seek a simple and cost-effective method for prevention and treatment of phlebitis. We investigated the roles of mirabilite in preventing and treating phlebitis caused by intravenous indwelling needles and provide guidance for prevention and treatment of mechanical phlebitis caused by intravenous indwelling needles. A total of 57 healthy congeneric big-eared New Zealand rabbits were randomly divided into 3 groups: blank control, indwelling needle, and group with external application of mirabilite. The ear vein of each rabbit was punctured with an intravenous indwelling needle. The ear vein specimens were taken at 3, 5, and 7 days after indwelling. The hematoxylin and eosin stained pathological tissue sections of the ear veins of the rabbits in each group were observed. The expression levels of IL-1 and IL-6, and tumour necrosis factor-α (TNF-α) in the vascular tissue of the ear veins of the rabbits in each group were detected with the immunofluorescence method. In the blank control group, there was no inflammatory cellular infiltration and no proliferation of fibrous tissue around the vascular wall. With the increase of the indwelling time, proliferation of fibrous tissue in vascular wall, increased inflammatory cellular infiltration and organized thrombus in the vascular tissue occurred in the ear veins of the rabbits in the indwelling needle group and group with external application of mirabilite. Compared with the indwelling needle group, the group with external application of mirabilite had significantly decreased fibrous tissue in the vascular wall and significantly decreased inflammatory cellular infiltration. At the same point in indwelling time, the expression levels of IL-1, IL-6, and TNF-α in the indwelling needle and group with external application of mirabilite were significantly higher than that in the blank control group (P<0.05). The expression levels of IL-1, IL-6, and TNF-α in the group with external application of mirabilite were lower than that in the indwelling needle group (P<0.05). The expression levels of IL-1, IL-6, and TNF-α are positively correlated with the indwelling time within the same group at different points in time. In conclusion, external application of mirabilite can significantly decrease infiltration of venous inflammatory cells of the rabbit ear margin, proliferation of fibrous tissue and thrombosis in the vascular wall, significant decrease the expression levels of IL-1, IL-6, and TNF-α in the mechanical phlebitis caused by intravenous indwelling needles, and decrease the inflammatory responses of the ear veins of rabbits.

Vascular mechanics of the coronary artery

NASA Technical Reports Server (NTRS)

Veress, A. I.; Vince, D. G.; Anderson, P. M.; Cornhill, J. F.; Herderick, E. E.; Klingensmith, J. D.; Kuban, B. D.; Greenberg, N. L.; Thomas, J. D.

2000-01-01

This paper describes our research into the vascular mechanics of the coronary artery and plaque. The three sections describe the determination of arterial mechanical properties using intravascular ultrasound (IVUS), a constitutive relation for the arterial wall, and finite element method (FEM) models of the arterial wall and atheroma. METHODS: Inflation testing of porcine left anterior descending coronary arteries was conducted. The changes in the vessel geometry were monitored using IVUS, and intracoronary pressure was recorded using a pressure transducer. The creep and quasistatic stress/strain responses were determined. A Standard Linear Solid (SLS) was modified to reproduce the non-linear elastic behavior of the arterial wall. This Standard Non-linear Solid (SNS) was implemented into an axisymetric thick-walled cylinder numerical model. Finite element analysis models were created for five age groups and four levels of stenosis using the Pathobiological Determinants of Atherosclerosis Youth (PDAY) database. RESULTS: The arteries exhibited non-linear elastic behavior. The total tissue creep strain was epsilon creep = 0.082 +/- 0.018 mm/mm. The numerical model could reproduce both the non-linearity of the porcine data and time dependent behavior of the arterial wall found in the literature with a correlation coefficient of 0.985. Increasing age had a strong positive correlation with the shoulder stress level, (r = 0.95). The 30% stenosis had the highest shoulder stress due to the combination of a fully formed lipid pool and a thin cap. CONCLUSIONS: Studying the solid mechanics of the arterial wall and the atheroma provide important insights into the mechanisms involved in plaque rupture.

The vascular endothelium in diabetes--a therapeutic target?

PubMed

Mather, Kieren J

2013-03-01

Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function. We review the available literature presenting studies in humans, evaluating the effects of metabolically targeted and vascular targeted therapies on insulin action and systemic metabolism. Therapies that improve systemic insulin resistance exert strong concurrent effects to improve vascular function and vascular insulin action. RAS-acting agents and statins have widely recognized beneficial effects on vascular function but have not uniformly produced the hoped-for metabolic benefits. These observations support the notion that systemic metabolic benefits can arise from therapies targeted at the endothelium, but improving vascular insulin action does not result from all treatments that improve endothelium-dependent vasodilation. A better understanding of the mechanisms of insulin's actions in the vascular wall will advance our understanding of the specificity of these responses, and allow us to better target the vasculature for metabolic benefits.

Sulfated Polysaccharides in the Freshwater Green Macroalga Cladophora surera Not Linked to Salinity Adaptation

PubMed Central

Arata, Paula X.; Alberghina, Josefina; Confalonieri, Viviana; Errea, María I.; Estevez, José M.; Ciancia, Marina

2017-01-01

The presence of sulfated polysaccharides in cell walls of seaweeds is considered to be a consequence of the physiological adaptation to the high salinity of the marine environment. Recently, it was found that sulfated polysaccharides were present in certain freshwater Cladophora species and some vascular plants. Cladophora (Ulvophyceae, Chlorophyta) is one of the largest genera of green algae that are able to grow in both, seas and freshwater courses. Previous studies carried out on the water-soluble polysaccharides of the marine species C. falklandica established the presence of sulfated xylogalactoarabinans constituted by a backbone of 4-linked β-L-arabinopyranose units partially sulfated mainly on C3 and also on C2 with partial glycosylation, mostly on C2, with terminal β-D-xylopyranose or β-D-galactofuranose units. Besides, minor amounts of 3-, 6- and/or 3,6-linked β-D-galactan structures, with galactose in the pyranosic form were detected. In this work, the main water soluble cell wall polysaccharides from the freshwater alga Cladophora surera were characterized. It was found that this green alga biosynthesizes sulfated polysaccharides, with a structure similar to those found in marine species of this genus. Calibration of molecular clock with fossil data suggests that colonization of freshwater environments occurred during the Miocene by its ancestor. Therefore, the presence of sulfated polysaccharides in the freshwater green macroalga C. surera could be, in this case, an adaptation to transient desiccation and changes in ionic strength. Retention of sulfated polysaccharides at the cell walls may represent a snapshot of an evolutionary event, and, thus constitutes an excellent model for further studies on the mechanisms of sulfation on cell wall polysaccharides and environmental stress co-evolution. PMID:29181012

Sulfated Polysaccharides in the Freshwater Green Macroalga Cladophora surera Not Linked to Salinity Adaptation.

PubMed

Arata, Paula X; Alberghina, Josefina; Confalonieri, Viviana; Errea, María I; Estevez, José M; Ciancia, Marina

2017-01-01

The presence of sulfated polysaccharides in cell walls of seaweeds is considered to be a consequence of the physiological adaptation to the high salinity of the marine environment. Recently, it was found that sulfated polysaccharides were present in certain freshwater Cladophora species and some vascular plants. Cladophora (Ulvophyceae, Chlorophyta) is one of the largest genera of green algae that are able to grow in both, seas and freshwater courses. Previous studies carried out on the water-soluble polysaccharides of the marine species C. falklandica established the presence of sulfated xylogalactoarabinans constituted by a backbone of 4-linked β-L-arabinopyranose units partially sulfated mainly on C3 and also on C2 with partial glycosylation, mostly on C2, with terminal β-D-xylopyranose or β-D-galactofuranose units. Besides, minor amounts of 3-, 6- and/or 3,6-linked β-D-galactan structures, with galactose in the pyranosic form were detected. In this work, the main water soluble cell wall polysaccharides from the freshwater alga Cladophora surera were characterized. It was found that this green alga biosynthesizes sulfated polysaccharides, with a structure similar to those found in marine species of this genus. Calibration of molecular clock with fossil data suggests that colonization of freshwater environments occurred during the Miocene by its ancestor. Therefore, the presence of sulfated polysaccharides in the freshwater green macroalga C. surera could be, in this case, an adaptation to transient desiccation and changes in ionic strength. Retention of sulfated polysaccharides at the cell walls may represent a snapshot of an evolutionary event, and, thus constitutes an excellent model for further studies on the mechanisms of sulfation on cell wall polysaccharides and environmental stress co-evolution.

The umbilical and paraumbilical veins of man.

PubMed

Martin, B F; Tudor, R G

1980-03-01

During its transit through the umbilicus structural changes occur in the thick wall of the extra-abdominal segment of the umbilical vein whereby the components of the intra-abdominal segment acquire an essentially longitudinal direction and become arranged in fibro-elastic and fibro-muscular zones. The vein lumen becomes largely obliterated by asymmetrical proliferation of loose subendothelial conective tissue. The latter forms a new inner zone within which a small segment of the lumen persists in an eccentric position. This residual lumen transmits blood to the portal system from paraumbilical and systemic sources, and is retained in the upper part of the vein, even in old age. A similar process of lumen closure is observed in the ductus venosus. In early childhood the lower third of the vein undergoes breakdown, with fatty infiltration, resulting in its complete division into vascular fibro-elastic strands, and in old age some breakdown occurs in the outermost part of the wall of the upper two thirds. The paraumbilical veins are thick-walled and of similar structure to the umbilical vein. Together they constitute an accessory portal system which is confined between the layers of the falciform ligament and is in communication with the veins of the ventral abdominal wall. The constituents form an ascending series, namely, Burow's veins, the umbilical vein, and Sappey's inferior and superior veins. The main channel of Sappey's inferior veins may be the remnant of the right umbilical vein since it communicates with the right rectus sheath and often communicates directly with the portal system within the right lobe of the liver. The results are of significance in relation to clinical usage of the umbilical vein.

Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

PubMed Central

Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

2013-01-01

Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

Basic Components of Vascular Connective Tissue and Extracellular Matrix.

PubMed

Halper, Jaroslava

2018-01-01

Though the composition of the three layers constituting the blood vessel wall varies among the different types of blood vessels, and some layers may even be missing in capillaries, certain basic components, and properties are shared by all blood vessels, though each histologically distinct layer contains a unique complement of extracellular components, growth factors and cytokines, and cell types as well. The structure and composition of vessel layers informs and is informed by the function of the particular blood vessel. The adaptation of the composition and the resulting function of the extracellular matrix (ECM) to changes in circulation/blood flow and a variety of other extravascular stimuli can be characterized as remodeling spearheaded by vascular cells. There is a surprising amount of cell traffic among the three layers. It starts with endothelial cell mediated transmigration of inflammatory cells from the bloodstream into the subendothelium, and then into tissue adjoining the blood vessel. Smooth muscle cells and a variety of adventitial cells reside in tunica media and tunica externa, respectively. The latter cells are a mixture of progenitor/stem cells, fibroblasts, myofibroblasts, pericytes, macrophages, and dendritic cells and respond to endothelial injury by transdifferentiation as they travel into the two inner layers, intima and media for corrective mission in the ECM composition. This chapter addresses the role of various vascular cell types and ECM components synthesized by them in maintenance of normal structure and in their contribution to major pathological processes, such as atherosclerosis, organ fibrosis, and diabetic retinopathy. © 2018 Elsevier Inc. All rights reserved.

SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging.

PubMed

Zarzuelo, María José; López-Sepúlveda, Rocío; Sánchez, Manuel; Romero, Miguel; Gómez-Guzmán, Manuel; Ungvary, Zoltan; Pérez-Vizcaíno, Francisco; Jiménez, Rosario; Duarte, Juan

2013-05-01

Vascular aging is characterized by up-regulation of NADPH oxidase, oxidative stress and endothelial dysfunction. Previous studies demonstrate that the activity of the evolutionarily conserved NAD(+)-dependent deacetylase SIRT1 declines with age and that pharmacological activators of SIRT1 confer significant anti-aging cardiovascular effects. To determine whether dysregulation of SIRT1 promotes NADPH oxidase-dependent production of reactive oxygen species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of SIRT1 (nicotinamide, sirtinol, EX527) in aorta segments isolated from young Wistar rats. Inhibition of SIRT1 induced endothelial dysfunction, as shown by the significantly reduced relaxation to the endothelium-dependent vasodilators acetylcholine and the calcium ionophore A23187. Endothelial dysfunction induced by SIRT1 inhibition was prevented by treatment of the vessels with the NADPH oxidase inhibitor apocynin or superoxide dismutase. Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by resveratrol. Peroxisome proliferator-activated receptor-α (PPARα) activation mimicked the effects of resveratrol while PPARα inhibition prevented the effects of this SIRT1 activator. SIRT1 co-precipitated with PPARα and nicotinamide increased the acetylation of the PPARα coactivator PGC-1α, which was suppressed by resveratrol. In conclusion, impaired activity of SIRT1 induces endothelial dysfunction and up-regulates NADPH oxidase-derived ROS production in the vascular wall, mimicking the vascular aging phenotype. Moreover, a new mechanism for controlling endothelial function after SIRT1 activation involves a decreased PGC-1α acetylation and the subsequent PPARα activation, resulting in both decreased NADPH oxidase-driven ROS production and NO inactivation. Copyright © 2013 Elsevier Inc. All rights reserved.

Physics of vascular brachytherapy.

PubMed

Jani, S K

1999-08-01

Basic physics plays an important role in understanding the clinical utility of radioisotopes in brachytherapy. Vascular brachytherapy is a very unique application of localized radiation in that dose levels very close to the source are employed to treat tissues within the arterial wall. This article covers basic physics of radioactivity and differentiates between beta and gamma radiations. Physical parameters such as activity, half-life, exposure and absorbed dose have been explained. Finally, the dose distribution around a point source and a linear source is described. The principles of basic physics are likely to play an important role in shaping the emerging technology and its application in vascular brachytherapy.

Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link.

PubMed

Hernández, Domingo; Triñanes, Javier; Armas, Ana María; Ruiz-Esteban, Pedro; Alonso-Titos, Juana; Duarte, Ana; González-Molina, Miguel; Palma, Eulalia; Salido, Eduardo; Torres, Armando

2017-07-01

Kidney transplant (KT) is the treatment of choice for most patients with chronic kidney disease, but this has a high cardiovascular mortality due to traditional and nontraditional risk factors, including vascular calcification. Inflammation could precede the appearance of artery wall lesions, leading to arteriosclerosis and clinical and subclinical atherosclerosis in these patients. Additionally, mineral metabolism disorders and activation of the renin-angiotensin system could contribute to this vascular damage. Thus, understanding the vascular lesions that occur in KT recipients and the pathogenic mechanisms involved in their development could be crucial to optimize the therapeutic management and outcomes in survival of this population. This review focuses on the following issues: (1) epidemiological data framing the problem; (2) atheromatosis in KT patients: subclinical and clinical atheromatosis, involving ischemic heart disease, congestive heart failure, stroke and peripheral vascular disease; (3) arteriosclerosis and vascular calcifications; and (4) potential pathogenic mechanisms and their therapeutic targets. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Volumetric three-dimensional intravascular ultrasound visualization using shape-based nonlinear interpolation

PubMed Central

2013-01-01

Background Intravascular ultrasound (IVUS) is a standard imaging modality for identification of plaque formation in the coronary and peripheral arteries. Volumetric three-dimensional (3D) IVUS visualization provides a powerful tool to overcome the limited comprehensive information of 2D IVUS in terms of complex spatial distribution of arterial morphology and acoustic backscatter information. Conventional 3D IVUS techniques provide sub-optimal visualization of arterial morphology or lack acoustic information concerning arterial structure due in part to low quality of image data and the use of pixel-based IVUS image reconstruction algorithms. In the present study, we describe a novel volumetric 3D IVUS reconstruction algorithm to utilize IVUS signal data and a shape-based nonlinear interpolation. Methods We developed an algorithm to convert a series of IVUS signal data into a fully volumetric 3D visualization. Intermediary slices between original 2D IVUS slices were generated utilizing the natural cubic spline interpolation to consider the nonlinearity of both vascular structure geometry and acoustic backscatter in the arterial wall. We evaluated differences in image quality between the conventional pixel-based interpolation and the shape-based nonlinear interpolation methods using both virtual vascular phantom data and in vivo IVUS data of a porcine femoral artery. Volumetric 3D IVUS images of the arterial segment reconstructed using the two interpolation methods were compared. Results In vitro validation and in vivo comparative studies with the conventional pixel-based interpolation method demonstrated more robustness of the shape-based nonlinear interpolation algorithm in determining intermediary 2D IVUS slices. Our shape-based nonlinear interpolation demonstrated improved volumetric 3D visualization of the in vivo arterial structure and more realistic acoustic backscatter distribution compared to the conventional pixel-based interpolation method. Conclusions This novel 3D IVUS visualization strategy has the potential to improve ultrasound imaging of vascular structure information, particularly atheroma determination. Improved volumetric 3D visualization with accurate acoustic backscatter information can help with ultrasound molecular imaging of atheroma component distribution. PMID:23651569

Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser1177/Thr497 of endothelial nitric oxide synthase in diabetic mice

PubMed Central

2014-01-01

Background Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), has a higher affinity for and slower dissociation from AT1 receptors and shows stronger inverse agonism compared to other ARBs. Possible benefits of azilsartan in diabetic vascular dysfunction have not been established. Methods We measured vascular reactivity of aortic rings in male KKAy diabetic mice treated with vehicle, 0.005% azilsartan, or 0.005% candesartan cilexetil for 3 weeks. Expression of markers of inflammation and oxidative stress was measured using semiquantitative RT-PCR in the vascular wall, perivascular fat, and skeletal muscle. Phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 and Thr495 was measured using Western blotting, and the ratio of phosphorylation at Ser1177 to phosphorylation at Thr495 was used as a putative indicator of vascular eNOS activity. Results (1) Vascular endothelium–dependent relaxation with acetylcholine in KKAy mice was improved by azilsartan treatment compared to candesartan cilexetil; (2) the ratio of Ser1177/Thr495 phosphorylation of eNOS was impaired in KKAy and was effectively restored by azilsartan; (3) anomalies in the expression levels of monocyte chemotactic protein 1 (MCP1), F4/80, NAD(P)H oxidase (Nox) 2, and Nox4 of the aortic wall and in the expression of TNFα in the perivascular fat were strongly attenuated by azilsartan compared to candesartan cilexetil. Conclusions These results provide evidence that azilsartan prevents endothelial dysfunction in diabetic mice, more potently than does candesartan cilexetil. Azilsartan’s higher affinity for and slower dissociation from AT1 receptors may underlie its efficacy in diabetic vascular dysfunction via a dual effect on uncoupled eNOS and on Nox. PMID:24485356

The role of heat shock proteins in protection and pathophysiology of the arterial wall.

PubMed

Xu, Q; Wick, G

1996-09-01

The arterial wall is an integrated functional component of the circulatory system that is continually remodelling in response to various stressors, including localized injury, toxins, smoking and hypercholesterolaemia. These stimuli directly or indirectly cause changes in blood pressure and damage to the vessel wall, and eventually induce arterial stiffness and obstruction. To maintain the homeostasis of the vessel wall, the vascular cells produce a high level of stress proteins, also known as heat shock proteins, which protect against damage during haemodynamic stress. However, an immune reaction to heat shock proteins might contribute to the development of atherosclerosis. We hypothesize that the induction of heat shock proteins is beneficial in the arterial wall's response to stress but is harmful in certain other circumstances.

Platelet chemokines in vascular disease

PubMed Central

Gleissner, Christian A.; von Hundelshausen, Philipp; Ley, Klaus

2009-01-01

Platelets are a rich source of different chemokines and express chemokine receptors. CXCL4 is highly abundant in platelets and involved in promoting monocyte arrest from rolling and monocyte differentiation to macrophages. CXCL4 can also associate with CCL5 and amplify its effect on monocytes. The megakaryocyte CXCL7 gene product is proteolytically cleaved into the strong neutrophil chemoattractant, NAP-2, which has also been implicated in repair cell homing to vascular lesions. Platelet adhesion can induce release of CCL2 and CXCL8 from endothelial cells. Conversely, the chemokines CCL17, CCL22 and CXCL12 made by other cells amplify platelet activation. Platelet chemokines enhance recruitment of various hematopoietic cells to the vascular wall, fostering processes such as neointima formation, atherosclerosis, and thrombosis but also vessel repair and regeneration after vascular injury. PMID:18723831

Physiological regulation of extracellular matrix collagen and elastin in the arterial wall of rats by noradrenergic tone and angiotensin II.

PubMed

Dab, Houcine; Kacem, Kamel; Hachani, Rafik; Dhaouadi, Nadra; Hodroj, Wassim; Sakly, Mohsen; Randon, Jacques; Bricca, Giampiero

2012-03-01

The interactions between the effects of the sympathetic nervous system (SNS) and angiotensin II (ANG II) on vascular extracellular matrix (ECM) synthesis were determined in rats. The mRNA and protein content of collagen I, collagen III and elastin in the abdominal aorta (AA) and femoral artery (FA) was investigated in Wistar-Kyoto rats treated for 5 weeks with guanethidine, a sympathoplegic, losartan, an ANG II AT1 receptor (AT1R) blocker, or both. The effects of noradrenaline (NE) and ANG II on collagen III and elastin mRNA, and the receptor involved, were tested in cultured vascular smooth muscle cells (VSMCs) in vitro. Guanethidine increased collagen types I and III and decreased elastin, while losartan had an opposite effect, although without effect on collagen III. The combination of treatments abrogated changes induced by simple treatment with collagen I and elastin, but increased collagen III mRNA in AA and not in FA. NE stimulated collagen III mRNA via β receptors and elastin via α1 and α2 receptors. ANG II stimulated collagen III but inhibited elastin mRNA via AT1R. Overall, SNS and ANG II exert opposite and antagonistic effects on major components of ECM in the vascular wall. This may be of relevance for the choice of a therapeutic strategy in vascular diseases.

Association of vascular fluoride uptake with vascular calcification and coronary artery disease.

PubMed

Li, Yuxin; Berenji, Gholam R; Shaba, Wisam F; Tafti, Bashir; Yevdayev, Ella; Dadparvar, Simin

2012-01-01

The feasibility of a fluoride positron emission tomography/computed tomography (PET/CT) scan for imaging atherosclerosis has not been well documented. The purpose of this study was to assess fluoride uptake of vascular calcification in various major arteries, including coronary arteries. We retrospectively reviewed the imaging data and cardiovascular history of 61 patients who received whole-body sodium [¹⁸F]fluoride PET/CT studies at our institution from 2009 to 2010. Fluoride uptake and calcification in major arteries, including coronary arteries, were analyzed by both visual assessment and standardized uptake value measurement. Fluoride uptake in vascular walls was demonstrated in 361 sites of 54 (96%) patients, whereas calcification was observed in 317 sites of 49 (88%) patients. Significant correlation between fluoride uptake and calcification was observed in most of the arterial walls, except in those of the abdominal aorta. Fluoride uptake in coronary arteries was demonstrated in 28 (46%) patients and coronary calcifications were observed in 34 (56%) patients. There was significant correlation between history of cardiovascular events and presence of fluoride uptake in coronary arteries. The coronary fluoride uptake value in patients with cardiovascular events was significantly higher than in patients without cardiovascular events. sodium [¹⁸F]fluoride PET/CT might be useful in the evaluation of the atherosclerotic process in major arteries, including coronary arteries. An increased fluoride uptake in coronary arteries may be associated with an increased cardiovascular risk.

Vascularization, high-volume solution flow, and localized roles for enzymes of sucrose metabolism during tumorigenesis by Agrobacterium tumefaciens.

PubMed

Wächter, Rebecca; Langhans, Markus; Aloni, Roni; Götz, Simone; Weilmünster, Anke; Koops, Ariane; Temguia, Leopoldine; Mistrik, Igor; Pavlovkin, Jan; Rascher, Uwe; Schwalm, Katja; Koch, Karen E; Ullrich, Cornelia I

2003-11-01

Vascular differentiation and epidermal disruption are associated with establishment of tumors induced by Agrobacterium tumefaciens. Here, we address the relationship of these processes to the redirection of nutrient-bearing water flow and carbohydrate delivery for tumor growth within the castor bean (Ricinus communis) host. Treatment with aminoethoxyvinyl-glycine showed that vascular differentiation and epidermal disruption were central to ethylene-dependent tumor establishment. CO2 release paralleled tumor growth, but water flow increased dramatically during the first 3 weeks. However, tumor water loss contributed little to water flow to host shoots. Tumor water loss was followed by accumulation of the osmoprotectants, sucrose (Suc) and proline, in the tumor periphery, shifting hexose-to-Suc balance in favor of sugar signals for maturation and desiccation tolerance. Concurrent activities and sites of action for enzymes of Suc metabolism changed: Vacuolar invertase predominated during initial import of Suc into the symplastic continuum, corresponding to hexose concentrations in expanding tumors. Later, Suc synthase (SuSy) and cell wall invertase rose in the tumor periphery to modulate both Suc accumulation and descending turgor for import by metabolization. Sites of abscisic acid immunolocalization correlated with both central vacuolar invertase and peripheral cell wall invertase. Vascular roles were indicated by SuSy immunolocalization in xylem parenchyma for inorganic nutrient uptake and in phloem, where resolution allowed SuSy identification in sieve elements and companion cells, which has widespread implications for SuSy function in transport. Together, data indicate key roles for ethylene-dependent vascularization and cuticular disruption in the redirection of water flow and carbohydrate transport for successful tumor establishment.

CNS pericytes: concepts, misconceptions, and a way out.

PubMed

Krueger, Martin; Bechmann, Ingo

2010-01-01

Rouget, in 1873, was the first to describe a population of cells surrounding capillaries, which he regarded as contractile elements. Fifty years later, Zimmermann termed these cells "pericytes" and distinguished three subtypes along the vascular tree. Since then, the discussion concerning the contractile ability of pericytes has never ceased. Current concepts of pericyte biology rather suggest critical roles in the maintenance of homeostasis, blood-brain barrier (BBB) integrity, angiogenesis, and neovascularization. In addition, data from models of brain pathology suggest that novel pericytes are recruited from the bone marrow, but their respective precursor remains enigmatic. Recent data also suggest an important role in the regulation of cerebral blood flow, thus confirming Rouget's original idea. However, comparison of data from different studies is often constrained by the fact that pericytes were questionably identified. Although a clear-cut definition exists, defining pericytes as part of the vascular wall being enclosed in its basement membrane, pericytes are often mixed up with adjacent cell types of the vascular wall, the perivascular space, and the juxtavascular parenchyma. In fact, their identification is difficult-if not impossible-in standard histological sections. An unambiguous distinction, however, is possible at the ultrastructural level and in semi-thin sections, where their location within the vascular basement membrane can be displayed. Using these techniques in combination with immunological staining methods allows demarking their unique morphology and location. Here, we review original papers describing pericytes, briefly outline their topography within the vascular compartments, describe methods for their identification, and summarize current concepts of their function. (c) 2009 Wiley-Liss, Inc.

Feasibility study on retinal vascular bypass surgery in isolated arterially perfused caprine eye model

PubMed Central

Chen, Y; Wu, W; Zhang, X; Fan, W; Shen, L

2011-01-01

Purpose To investigate the feasibility of bypassing occluded segments of retinal venous main vessels in isolated, arterially perfused caprine eyes via the closed-sky vitrectomy approach using keratoprosthesis. Methods Isolated caprine eyes were used in this study. For each eye, the retinal vessel was perfused by Krebs solution via ophthalmic artery, and pars plana vitrectomy was performed using temporary keratoprosthesis. All retinal micro-vascular maneuvers were performed in a closed-sky eyeball. The main retinal vein was blocked by endodiathermy at the site of the vessel's first branching. Two openings, several millimeters apart, were created by vascular punctures in both the main vein and its branch vein wall straddling the induced occluded segment. Catheterization was achieved using a flexible polyimide tube, with each end inserted into the vessel wall opening. A sealed connection between the vessel and the tube was obtained by endodiathermy. Bypass of the occluded retinal vein segment was thus achieved, and the patency of this vascular bypass was confirmed by intravascular staining. Results Puncturing, catheterization, and endodiathermy were viable by closed-sky approach using keratoprosthesis. Bypassing of the occluded retinal main vein segment was accomplished with the combination of these maneuvers. Good results were obtained in 23 of 38 (60%) caprine eyes. Conclusions This study demonstrated that bypassing the occluded segment of retinal main vein can be successfully performed in a closed-sky eyeball model of isolated, arterially perfused caprine eye. This early work indicated that the more advanced retinal vascular bypass surgery in in vivo eye may be feasible in the future. PMID:21921946

Optimizing 18F-FDG PET/CT Imaging of Vessel Wall Inflammation –The Impact of 18F-FDG Circulation Time, Injected Dose, Uptake Parameters, and Fasting Blood Glucose Levels

PubMed Central

Bucerius, Jan; Mani, Venkatesh; Moncrieff, Colin; Machac, Josef; Fuster, Valentin; Farkouh, Michael E.; Tawakol, Ahmed; Rudd, James H. F.; Fayad, Zahi A.

2014-01-01

Purpose 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used for imaging of vessel wall inflammation. However, limited data is available regarding the impact of methodological variables, i. e. patient’s pre-scan fasting glucose, the FDG circulation time, the injected FDG dose, and of different FDG uptake parameters, in vascular FDG-PET imaging. Methods 195 patients underwent vascular FDG-PET/CT of the aorta and the carotids. Arterial standard uptake values (meanSUVmax) as well as target-to-background-ratios (meanTBRmax) and the FDG blood pool activity in the superior vein cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake classified according to tertiles of patient’s pre-scan fasting glucose levels, the FDG circulation time, and the injected FDG dose was compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood pool FDG uptake. Results Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l showing favorable relations between the arterial and blood pool FDG uptake. FDG circulation times showed negative associations with the aortic meanSUVmax values as well as SVC- and JV FDG blood pool activity but a positive correlation with the aortic- and carotid meanTBRmax values. Pre-scan glucose was negatively associated with aortic- and carotid meanTBRmax and carotid meanSUVmax values, but correlated positively with the SVC blood pool uptake. Injected FDG dose failed to show any significant association with the vascular FDG uptake. Conclusion FDG circulation times and pre-scan blood glucose levels significantly impact FDG uptake within the aortic and carotid wall and may bias the results of image interpretation in patients undergoing vascular FDG-PET/CT. FDG dose injected was less critical. Therefore, circulation times of about 2.5 h and pre-scan glucose levels less than 7.0 mmol/l should be preferred in this setting. PMID:24271038

Beyond Frangi: an improved multiscale vesselness filter

NASA Astrophysics Data System (ADS)

Jerman, Tim; Pernuš, Franjo; Likar, Boštjan; Špiclin, Žiga

2015-03-01

Vascular diseases are among the top three causes of death in the developed countries. Effective diagnosis of vascular pathologies from angiographic images is therefore very important and usually relies on segmentation and visualization of vascular structures. To enhance the vascular structures prior to their segmentation and visualization, and to suppress non-vascular structures and image noise, the filters enhancing vascular structures are used extensively. Even though several enhancement filters are widely used, the responses of these filters are typically not uniform between vessels of different radii and, compared to the response in the central part of vessels, their response is lower at vessels' edges and bifurcations, and vascular pathologies like aneurysm. In this paper, we propose a novel enhancement filter based on ratio of multiscale Hessian eigenvalues, which yields a close-to-uniform response in all vascular structures and accurately enhances the border between the vascular structures and the background. The proposed and four state-of-the-art enhancement filters were evaluated and compared on a 3D synthetic image containing tubular structures and a clinical dataset of 15 cerebral 3D digitally subtracted angiograms with manual expert segmentations. The evaluation was based on quantitative metrics of segmentation performance, computed as area under the precision-recall curve, signal-to-noise ratio of the vessel enhancement and the response uniformity within vascular structures. The proposed filter achieved the best scores in all three metrics and thus has a high potential to further improve the performance of existing or encourage the development of more advanced methods for segmentation and visualization of vascular structures.

An ex vivo investigation into the transurothelial permeability and bladder wall distribution of the nonsteroidal anti-inflammatory ketorolac.

PubMed

Williams, Nicholas A; Bowen, Jenna L; Al-Jayyoussi, Ghaith; Gumbleton, Mark; Allender, Chris J; Li, Jamie; Harrah, Tim; Raja, Aditya; Joshi, Hrishi B

2014-03-03

Transurothelial drug delivery continues to be an attractive treatment option for a range of urological conditions; however, dosing regimens remain largely empirical. Recently, intravesical delivery of the nonsteroidal anti-inflammatory ketorolac has been shown to significantly reduce ureteral stent-related pain. While this latest development provides an opportunity for advancing the management of stent-related pain, clinical translation will undoubtedly require an understanding of the rate and extent of delivery of ketorolac into the bladder wall. Using an ex vivo porcine model, we evaluate the urothelial permeability and bladder wall distribution of ketorolac. The subsequent application of a pharmacokinetic (PK) model enables prediction of concentrations achieved in vivo. Ketorolac was applied to the urothelium and a transurothelial permeability coefficient (Kp) calculated. Relative drug distribution into the bladder wall after 90 min was determined. Ketorolac was able to permeate the urothelium (Kp = 2.63 × 10(-6) cm s(-1)), and after 90 min average concentrations of 400, 141 and 21 μg g(-1) were achieved in the urothelium, lamina propria and detrusor respectively. An average concentration of 87 μg g(-1) was achieved across the whole bladder wall. PK simulations (STELLA) were then carried out, using ex vivo values for Kp and muscle/saline partition coefficient (providing an estimation of vascular clearance), to predict 90 min in vivo ketorolac tissue concentrations. When dilution of the drug solution with urine and vascular clearance were taken into account, a reduced ketorolac concentration of 37 μg g(-1) across the whole bladder wall was predicted. These studies reveal crucial information about the urothelium's permeability to agents such as ketorolac and the concentrations achievable in the bladder wall. It would appear that levels of ketorolac delivered to the bladder wall intravesically would be sufficient to provide an anti-inflammatory effect. The combination of such ex vivo data and PK modeling provides an insight into the likelihood of achieving clinically relevant concentrations of drug following intravesical administration.

Cerebrovascular Manifestations of Neurosarcoidosis: An Underrecognized Aspect of the Imaging Spectrum.

PubMed

Bathla, G; Watal, P; Gupta, S; Nagpal, P; Mohan, S; Moritani, T

2017-12-28

Involvement of the central nervous system by sarcoidosis, also referred to as neurosarcoidosis, is seen clinically in about 5% of patients with systemic disease. CNS involvement most frequently affects the leptomeninges and cranial nerves, though the ventricular system, brain parenchyma, and pachymeninges may also be involved. Even though the involvement of the intracranial vascular structures is well-known on postmortem studies, there is scant literature on imaging manifestations secondary to the vessel wall involvement, being confined mostly to isolated case reports and small series. The authors present a review of various cerebrovascular manifestations of neurosarcoidosis, along with a brief synopsis of the existing literature. © 2018 by American Journal of Neuroradiology.

Breaking symmetry in non-planar bifurcations: distribution of flow and wall shear stress.

PubMed

Lu, Yiling; Lu, Xiyun; Zhuang, Lixian; Wang, Wen

2002-01-01

Non-planarity in blood vessels is known to influence arterial flows and wall shear stress. To gain insight, computational fluid dynamics (CFD) has been used to investigate effects of curvature and out-of-plane geometry on the distribution of fluid flows and wall shear stresses in a hypothetical non-planar bifurcation. Three-dimensional Navier-Stokes equations for a steady state Newtonian fluid were solved numerically using a finite element method. Non-planarity in one of the two daughter vessels is found to deflect flow from the inner wall of the vessel to the outer wall and to cause changes in the distribution of wall shear stresses. Results from this study agree to experimental observations and CFD simulations in the literature, and support the view that non-planarity in blood vessels is a factor with important haemodynamic significance and may play a key role in vascular biology and pathophysiology.

An improved method based on wavelet coefficient correlation to filter noise in Doppler ultrasound blood flow signals

NASA Astrophysics Data System (ADS)

Wan, Renzhi; Zu, Yunxiao; Shao, Lin

2018-04-01

The blood echo signal maintained through Medical ultrasound Doppler devices would always include vascular wall pulsation signal .The traditional method to de-noise wall signal is using high-pass filter, which will also remove the lowfrequency part of the blood flow signal. Some scholars put forward a method based on region selective reduction, which at first estimates of the wall pulsation signals and then removes the wall signal from the mixed signal. Apparently, this method uses the correlation between wavelet coefficients to distinguish blood signal from wall signal, but in fact it is a kind of wavelet threshold de-noising method, whose effect is not so much ideal. In order to maintain a better effect, this paper proposes an improved method based on wavelet coefficient correlation to separate blood signal and wall signal, and simulates the algorithm by computer to verify its validity.

Systemic acquired resistance in moss: further evidence for conserved defense mechanisms in plants.

PubMed

Winter, Peter S; Bowman, Collin E; Villani, Philip J; Dolan, Thomas E; Hauck, Nathanael R

2014-01-01

Vascular plants possess multiple mechanisms for defending themselves against pathogens. One well-characterized defense mechanism is systemic acquired resistance (SAR). In SAR, a plant detects the presence of a pathogen and transmits a signal throughout the plant, inducing changes in the expression of various pathogenesis-related (PR) genes. Once SAR is established, the plant is capable of mounting rapid responses to subsequent pathogen attacks. SAR has been characterized in numerous angiosperm and gymnosperm species; however, despite several pieces of evidence suggesting SAR may also exist in non-vascular plants6-8, its presence in non-vascular plants has not been conclusively demonstrated, in part due to the lack of an appropriate culture system. Here, we describe and use a novel culture system to demonstrate that the moss species Amblystegium serpens does initiate a SAR-like reaction upon inoculation with Pythium irregulare, a common soil-borne oomycete. Infection of A. serpens gametophores by P. irregulare is characterized by localized cytoplasmic shrinkage within 34 h and chlorosis and necrosis within 7 d of inoculation. Within 24 h of a primary inoculation (induction), moss gametophores grown in culture became highly resistant to infection following subsequent inoculation (challenge) by the same pathogen. This increased resistance was a response to the pathogen itself and not to physical wounding. Treatment with β-1,3 glucan, a structural component of oomycete cell walls, was equally effective at triggering SAR. Our results demonstrate, for the first time, that this important defense mechanism exists in a non-vascular plant, and, together with previous studies, suggest that SAR arose prior to the divergence of vascular and non-vascular plants. In addition, this novel moss - pathogen culture system will be valuable for future characterization of the mechanism of SAR in moss, which is necessary for a better understanding of the evolutionary history of SAR in plants.

Dual effects of fructose on ChREBP and FoxO1/3α are responsible for AldoB up-regulation and vascular remodelling.

PubMed

Cao, Wei; Chang, Tuanjie; Li, Xiao-Qiang; Wang, Rui; Wu, Lingyun

2017-02-01

Increased production of methylglyoxal (MG) in vascular tissues is one of the causative factors for vascular remodelling in different subtypes of metabolic syndrome, including hypertension and insulin resistance. Fructose-induced up-regulation of aldolase B (AldoB) contributes to increased vascular MG production but the underlying mechanisms are unclear. Serum levels of MG and fructose were determined in diabetic patients with hypertension. MG level had significant positive correlations with blood pressure and fructose level respectively. C57BL/6 mice were fed with control or fructose-enriched diet for 3 months and ultrasonographic and histologic analyses were performed to evaluate arterial structural changes. Fructose-fed mice exhibited hypertension and high levels of serum MG with normal glucose level. Fructose intake increased blood vessel wall thickness and vascular smooth muscle cell (VSMC) proliferation. Western blotting and real-time PCR analysis revealed that AldoB level was significantly increased in both the aorta of fructose-fed mice and the fructose-treated VSMCs, whereas aldolase A (AldoA) expression was not changed. The knockdown of AldoB expression prevented fructose-induced MG overproduction and VSMC proliferation. Moreover, fructose significantly increased carbohydrate-responsive element-binding protein (ChREBP), phosphorylated FoxO1/3α and Akt1 levels. Fructose induced translocation of ChREBP from the cytosol to nucleus and activated AldoB gene expression, which was inhibited by the knockdown of ChREBP. Meanwhile, fructose caused FoxO1/3α shuttling from the nucleus to cytosol and inhibited its binding to AldoB promoter region. Fructose-induced AldoB up-regulation was suppressed by Akt1 inhibitor but enhanced by FoxO1/3α siRNA. Collectively, fructose activates ChREBP and inactivates FoxO1/3α pathways to up-regulate AldoB expression and MG production, leading to vascular remodelling. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Numerical Models of Human Circulatory System under Altered Gravity: Brain Circulation

NASA Technical Reports Server (NTRS)

Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan; David, Tim

2003-01-01

A computational fluid dynamics (CFD) approach is presented to model the blood flow through the human circulatory system under altered gravity conditions. Models required for CFD simulation relevant to major hemodynamic issues are introduced such as non-Newtonian flow models governed by red blood cells, a model for arterial wall motion due to fluid-wall interactions, a vascular bed model for outflow boundary conditions, and a model for auto-regulation mechanism. The three-dimensional unsteady incompressible Navier-Stokes equations coupled with these models are solved iteratively using the pseudocompressibility method and dual time stepping. Moving wall boundary conditions from the first-order fluid-wall interaction model are used to study the influence of arterial wall distensibility on flow patterns and wall shear stresses during the heart pulse. A vascular bed modeling utilizing the analogy with electric circuits is coupled with an auto-regulation algorithm for multiple outflow boundaries. For the treatment of complex geometry, a chimera overset grid technique is adopted to obtain connectivity between arterial branches. For code validation, computed results are compared with experimental data for steady and unsteady non-Newtonian flows. Good agreement is obtained for both cases. In sin-type Gravity Benchmark Problems, gravity source terms are added to the Navier-Stokes equations to study the effect of gravitational variation on the human circulatory system. This computational approach is then applied to localized blood flows through a realistic carotid bifurcation and two Circle of Willis models, one using an idealized geometry and the other model using an anatomical data set. A three- dimensional anatomical Circle of Willis configuration is reconstructed from human-specific magnetic resonance images using an image segmentation method. The blood flow through these Circle of Willis models is simulated to provide means for studying gravitational effects on the brain circulation under auto-regulation.

Split Tolerance in a Murine Model of Heterotopic En Bloc Chest Wall Transplantation

PubMed Central

Oh, Byoungchol; Furtmüller, Georg J.; Malek, Veronika; Fryer, Madeline L.; Brayton, Cory; Walczak, Piotr; Janowski, Miroslaw

2017-01-01

Background: Congenital and acquired chest wall deformities represent a significant challenge to functional reconstruction and may impact feasibility of heart transplantation for patients with end-stage organ failure. In the recent past, the concept of replacing like-with-like tissue by using vascularized composite allografts (VCA) has been enthusiastically employed for reconstruction of complex tissue defects. Methods: In this study, we introduce a novel murine model for en bloc chest wall, heart, and thymus transplantation and thereby the use of complex tissue allografts for reconstruction of both chest wall defects and also end-stage organ failure. Additionally, this model allows us to study the features of combined vascularized bone marrow (VBM), thymus, and heart transplantation on allograft survival and function. Heterotopic chest wall, thymus, and heart transplants were performed in untreated syngeneic and allogeneic combinations and in allogeneic combinations treated with costimulation blockade (CTLA4-Ig and MR-1). Results: Indefinite (ie, 150 d, N = 3) graft survival was observed in syngeneic controls. In untreated recipients of allogeneic grafts, the skin component was rejected after 10 (±1) days, whereas rejection of the heart occurred after 13 (± 1) days (N = 3). Costimulation blockade treatment prolonged survival of the heart and chest wall component (130 d, N = 3) as well as the VBM niche as evidenced by donor-specific chimerism (average: 2.35 ± 1.44%), whereas interestingly, the skin component was rejected after 13 (±1) days. Conclusion: Thus, this novel microsurgical model of VCA combined with solid organ transplantation is technically feasible and results in split tolerance when treated with costimulatory blockade. PMID:29632774

Arterial Wall Imaging in Pediatric Stroke.

PubMed

Dlamini, Nomazulu; Yau, Ivanna; Muthusami, Prakash; Mikulis, David J; Elbers, Jorina; Slim, Mahmoud; Askalan, Rand; MacGregor, Daune; deVeber, Gabrielle; Shroff, Manohar; Moharir, Mahendranath

2018-04-01

Arteriopathy is common in childhood arterial ischemic stroke (AIS) and predicts stroke recurrence. Currently available vascular imaging techniques mainly image the arterial lumen rather than the vessel wall and have a limited ability to differentiate among common arteriopathies. We aimed to investigate the value of a magnetic resonance imaging-based technique, namely noninvasive arterial wall imaging (AWI), for distinguishing among arteriopathy subtypes in a consecutive cohort of children presenting with AIS. Children with confirmed AIS and magnetic resonance angiography underwent 3-Tesla AWI including T1-weighted 2-dimensional fluid-attenuated inversion recovery fast spin echo sequences pre- and post-gadolinium contrast. AWI characteristics, including wall enhancement, wall thickening, and luminal stenosis, were documented for all. Twenty-six children with AIS had AWI. Of these, 9 (35%) had AWI enhancement. AWI enhancement was associated with anterior circulation magnetic resonance angiography abnormality and cortical infarction in 8 of 9 (89%) children and normal magnetic resonance angiography with posterior circulation subcortical infarction in 1 (1 of 9; 11%) child. AWI enhancement was not seen in 17 (65%), 10 (59%) of whom had an abnormal magnetic resonance angiography. Distinct patterns of pre- and postcontrast signal abnormality were demonstrated in the vessel wall in the region of interest in children with transient cerebral arteriopathy, arterial dissection, primary central nervous system angiitis, dissecting aneurysm, and cardioembolic stroke. AWI is a noninvasive, high-resolution magnetic resonance AWI technique, which can be successfully used in children presenting with AIS. Patterns of AWI enhancement are recognizable and associated with specific AIS pathogeneses. Further studies are required to assess the additional diagnostic utility of AWI over routine vascular imaging techniques, in childhood AIS. © 2018 American Heart Association, Inc.

Laceration of the Common Femoral Artery Following Deployment of the StarClose{sup TM} Vascular Closure System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonsalves, Michael, E-mail: drmag1975@gmail.com; Walkden, Miles, E-mail: rwalkden@nhs.net; Belli, Anna Maria, E-mail: Anna.Belli@stgeorges.nhs.u

2008-07-15

StarClose is a novel arterial closure device which achieves hemostasis, following arteriotomy, via a nitinol clip deployed on the outer arterial wall. Since its introduction to the market, several studies have shown StarClose to be both safe and effective, with few major complications encountered. We report a case of common femoral artery laceration following deployment of the StarClose vascular closure system. We conclude that the injury occurred secondary to intravascular misplacement of the nitinol clip.

Participation of blood vessel cells in human adaptive immune responses.

PubMed

Pober, Jordan S; Tellides, George

2012-01-01

Circulating T cells contact blood vessels either when they extravasate across the walls of microvessels into inflamed tissues or when they enter into the walls of larger vessels in inflammatory diseases such as atherosclerosis. The blood vessel wall is largely composed of three cell types: endothelial cells lining the entire vascular tree; pericytes supporting the endothelium of microvessels; and smooth muscle cells forming the bulk of large vessel walls. Each of these cell types interacts with and alters the behavior of infiltrating T cells in different ways, making these cells active participants in the processes of immune-mediated inflammation. In this review, we compare and contrast what is known about the nature of these interactions in humans. Copyright © 2011 Elsevier Ltd. All rights reserved.

Open scapulothoracic dissociation.

PubMed

Fischer, P J; Kent, R B

2001-04-01

Scapulothoracic dissociation refers to the traumatic separation of the shoulder from the chest wall. This most commonly occurs as a closed injury. We present a case of open scapulothoracic dissociation and emphasize clinical features unique to this injury. In both closed and open scapulothoracic dissociation, the force necessary to shear the scapula from its thoracic attachments results in vascular disruption and neurologic injury to the upper extremity. As a consequence, patients have a pulseless, flail upper extremity with a significant chest wall hematoma (closed) or active bleeding (open). The first priority is to resuscitate and address life-threatening injuries. If the patient has active bleeding, immediate vascular control to prevent exsanguination is essential. Patients with ischemia and an incomplete injury or unreliable neurologic examination need revascularization. Outcome is based on the extent of brachial plexus or cervical nerve root avulsion. Patients with loss of neurologic function ultimately benefit from amputation at the appropriate level.

Ansys Fluent versus Sim Vascular for 4-D patient-specific computational hemodynamics in renal arteries

NASA Astrophysics Data System (ADS)

Mumbaraddi, Avinash; Yu, Huidan (Whitney); Sawchuk, Alan; Dalsing, Michael

2015-11-01

The objective of this clinical-need driven research is to investigate the effect of renal artery stenosis (RAS) on the blood flow and wall shear stress in renal arteries through 4-D patient-specific computational hemodynamics (PSCH) and search for possible critical RASs that significantly alter the pressure gradient across the stenosis by manually varying the size of RAS from 50% to 95%. The identification of the critical RAS is important to understand the contribution of RAS to the overall renal resistance thus appropriate clinical therapy can be determined in order to reduce the hypertension. Clinical CT angiographic data together with Doppler Ultra sound images of an anonymous patient are used serving as the required inputs of the PSCH. To validate the PSCH, we use both Ansys Fluent and Sim Vascular and compare velocity, pressure, and wall-shear stress under identical conditions. Renal Imaging Technology Development Program (RITDP) Grant.

The Vascular Wall: a Plastic Hub of Activity in Cardiovascular Homeostasis and Disease.

PubMed

Awgulewitsch, Cassandra P; Trinh, Linh T; Hatzopoulos, Antonis K

2017-06-01

This review aims to summarize recent findings regarding the plasticity and fate switching among somatic and progenitor cells residing in the vascular wall of blood vessels in health and disease. Cell lineage tracing methods have identified multiple origins of stem cells, macrophages, and matrix-producing cells that become mobilized after acute or chronic injury of cardiovascular tissues. These studies also revealed that in the disease environment, resident somatic cells become plastic, thereby changing their stereotypical identities to adopt proinflammatory and profibrotic phenotypes. Currently, the functional significance of this heterogeneity among reparative cells is unknown. Furthermore, mechanisms that control cellular plasticity and fate decisions in the disease environment are poorly understood. Cardiovascular diseases are responsible for the majority of deaths worldwide. From a therapeutic perspective, these novel discoveries may identify new targets to improve the repair and regeneration of the cardiovascular system.

Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model.

PubMed

Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

2017-07-01

: L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel-Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis.

Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model

PubMed Central

Dai, Bingyang; Li, Lan; Li, Qiangqiang; Song, Xiaoxiao; Chen, Dongyang; Dai, Jin; Yao, Yao; Yan, Wenjin; Teng, Huajian; Yang, Fang; Xu, Zhihong; Jiang, Qing

2017-01-01

L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel–Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model. Thrombosis of the inferior vena cava was induced by applying a piece of filter paper (5 mm × 10 mm) saturated with 10% FeCl3 solution for 5 min. Targeted microspheres with L-arg, targeted microspheres with water, and saline were injected into the tail veins of the rats after 30 min of applying the filter paper saturated with 10% FeCl3 solution. The dry weight and length of the thrombus isolated from the inferior vena cava were significantly decreased in the group with L-arg in microsphere after 24 h. No significant differences in prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen among the groups were indicated. Images revealed that apoptosis in the vascular wall was less in the group injected with targeted microspheres with L-arg than in the other two groups at 1 and 8 d postsurgery. Meanwhile, cell proliferation was considerably excessive in the group injected with L-arg wrapped in targeted microspheres. Therefore, these novel microspheres could decrease the formation of thrombus in the early stages and in the subsequent periods of thrombosis. The microspheres can also enhance the vitality of impaired endothelial cells and reduce cell apoptosis. PMID:28306627

[Hepatic artery of the rat in experimental cirrhosis of the liver].

PubMed

Baĭbekov, I M; Vorozheĭkin, V M; Khoroshaev, V A; Khamidov, P M

1984-04-01

In 30 male rats of Wistar strain (20 more rats served as controls) thickness of the internal elastic membrane, that of the media, cross section area of the media and that of the lumen were define 3, 4, 5 and 6 months after the experiment was started. The initial changes in the hepatic artery structure are noted on the 4th month, however, differences in the parameters are not yet statistically significant. On the 5th month certain signs of hypertrophy in the smooth muscle cells of the media are clearly seen, as well as an increasing thickness of the internal elastic membrane and that of the tunica media. Simultaneously, the index of labelling the myocyte nuclei reaches its maximum. The increasing thickness of the arterial wall causes certain decrease in the lumen cross section area. The changes of all the parameters are statistically significant. In 6 months after the beginning of the experiment, a pronounced hyperelastosis develops in the wall of the hepatic artery; a part of the smooth muscle cells in the tunica media undergoes atrophy. The area of the vascular lumen decreases by 16%, comparing to the age control. The experimental data confirm certain clinical observations and reveal some features in the mechanism of pathological changes occurring in the hepatic artery wall at cirrhosis.

Measurement of retinal wall-to-lumen ratio by adaptive optics retinal camera: a clinical research.

PubMed

Meixner, Eva; Michelson, Georg

2015-11-01

To measure the wall-to-lumen ratio (WLR) and the cross-sectional area of the vascular wall (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera. Forty-seven human subjects were examined and their medical history was explored. WLR and WCSA were measured on the basis of retinal arteriolar wall thickness (VW), lumen diameter (LD) and vessel diameter (VD) assessed by rtx1 Adaptive Optics retinal camera. WLR was calculated by the formula [Formula: see text]. Arterio-venous ratio (AVR) and microvascular abnormalities were attained by quantitative and qualitative assessment of fundus photographs. Influence of age, arterial hypertension, body mass index (BMI) and retinal microvascular abnormalities on the WLR was examined. An age-adjusted WLR was created to test influences on WLR independently of age. Considering WLR and WCSA, a distinction between eutrophic and hypertrophic retinal remodeling processes was possible. The intra-observer variability (IOV) was 6 % ± 0.9 for arteriolar wall thickness and 2 % ± 0.2 for arteriolar wall thickness plus vessel lumen. WLR depended significantly on the wall thickness (r = 0.715; p < 0.01) of retinal arterioles, but was independent of the total vessel diameter (r = 0.052; p = 0.728). WLR correlated significantly with age (r = 0.769; p < 0.01). Arterial hypertension and a higher BMI were significantly associated with an increased age-adjusted WLR. WLR correlated significantly with the stage of microvascular abnormalities. 55 % of the hypertensive subjects and 11 % of the normotensive subjects showed eutrophic remodeling, while hypertrophic remodeling was not detectable. WLR correlated inversely with AVR. AVR was independent of the arteriolar wall thickness, age and arterial hypertension. The technique of AO retinal imaging allows a direct measurement of the retinal vessel wall and lumen diameter with good intra-observer variability. Age, arterial hypertension and an elevated BMI level are significantly associated with an increased WLR. The wall-to-lumen ratio measured by AO can be used to detect structural retinal microvascular alterations in an early stage of remodeling processes.

Vessel wall characterization using quantitative MRI: what's in a number?

PubMed

Coolen, Bram F; Calcagno, Claudia; van Ooij, Pim; Fayad, Zahi A; Strijkers, Gustav J; Nederveen, Aart J

2018-02-01

The past decade has witnessed the rapid development of new MRI technology for vessel wall imaging. Today, with advances in MRI hardware and pulse sequences, quantitative MRI of the vessel wall represents a real alternative to conventional qualitative imaging, which is hindered by significant intra- and inter-observer variability. Quantitative MRI can measure several important morphological and functional characteristics of the vessel wall. This review provides a detailed introduction to novel quantitative MRI methods for measuring vessel wall dimensions, plaque composition and permeability, endothelial shear stress and wall stiffness. Together, these methods show the versatility of non-invasive quantitative MRI for probing vascular disease at several stages. These quantitative MRI biomarkers can play an important role in the context of both treatment response monitoring and risk prediction. Given the rapid developments in scan acceleration techniques and novel image reconstruction, we foresee the possibility of integrating the acquisition of multiple quantitative vessel wall parameters within a single scan session.

Myocytes of chorionic vessels from placentas with meconium-associated vascular necrosis exhibit apoptotic markers.

PubMed

King, Erin L; Redline, Raymond W; Smith, Steven D; Kraus, Frederick T; Sadovsky, Yoel; Nelson, D Michael

2004-04-01

Meconium-associated vascular necrosis (MAVN) is a histological abnormality of human placental chorionic vessels that is associated with poor neonatal outcome. We tested the hypothesis that MAVN shows apoptosis in the walls of chorionic vessels. Archival placental specimens with MAVN (n = 5) were compared with specimens from uncomplicated pregnancies at term (n = 5) and from placentas with intense chorionic vasculitis associated with acute chorioamnionitis with (n = 5) or without (n = 5) a clinical history of meconium in the amniotic fluid. Sections from all placentas were processed by the TUNEL method, and 2 observers who were blinded to specimen diagnosis quantified the immunofluorescent TUNEL staining in both the amnion-facing and villous-facing walls of the larger chorionic vessels in each specimen. Compared with the other 3 groups, only the amnion-facing wall of chorionic vessels in MAVN showed a significantly greater number of apoptotic cells. This was verified by morphological criteria and caspase 3 staining. There were limited or no detectable TUNEL-stained cells in either the villous-facing walls of vessels in the MAVN specimens or in any of the vessels of the placentas from uncomplicated pregnancies. There was a negligible level of apoptosis in chorionic vessels of placentas with intense chorionic vasculitis, with or without meconium, despite the inflammatory response or presence of meconium. We conclude that apoptosis contributes to the pathophysiology of MAVN.

Gender Differences in Bed Rest: Preliminary Analysis of Vascular Function

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Stenger, Michael B.; Martin, David S.; Freeman-Perez, Sondra A.; Phillips, Tiffany; Ribeiro, L. Christine

2008-01-01

Orthostatic intolerance is a recognized consequence of spaceflight. Numerous studies have shown that women are more susceptible to orthostatic intolerance following spaceflight as well as bed rest, the most commonly used ground-based analog for spaceflight. One of the possible mechanisms proposed to account for this is a difference in vascular responsiveness between genders. We hypothesized that women and men would have differing vascular responses to 90 days of 6-degree head down tilt bed rest. Additionally, we hypothesized that vessels in the upper and lower body would respond differently, as has been shown in the animal literature. Thirteen subjects were placed in bedrest for 90 days (8 men, 5 women) at the Flight Analogs Unit, UTMB. Direct arterial and venous measurements were made with ultrasound to evaluate changes in vascular structure and function. Arterial function was assessed, in the arm and leg, during a reactive hyperemia protocol and during sublingual nitroglycerin administration to gauge the contributions of endothelial dependent and independent dilator function respectively. Venous function was assessed in dorsal hand and foot veins during the administration of pharmaceuticals to assess constrictor and dilator function. Both gender and day effects are seen in arterial dilator function to reactive hyperemia, but none are seen with nitroglycerin. There are also differences in the wall thickness in the arm vs the leg during bed rest, which return toward pre-bed rest levels by day 90. More subjects are required, especially females as there is not sufficient power to properly analyze venous function. Day 90 data are most underpowered.

Hypoxia induced VEGF synthesis in visceral adipose depots of obese diabetic patients.

PubMed

Fusaru, Ana Marina; Pisoschi, Cătălina Gabriela; Bold, Adriana; Taisescu, C; Stănescu, R; Hîncu, Mihaela; Crăiţoiu, Stefania; Baniţă, Ileana Monica

2012-01-01

VEGF is one the pro-inflammatory adipokines synthesized by the "adipose secretoma" of obese subjects as a response to hypoxic conditions; but the main function of VEGF is angiogenesis, being recognized as the most important factor increasing blood capillaries in the adipose tissue by stimulating endothelial cell growth. In this paper, we propose a comparative study of the vascular response to VEGF synthesis in the subcutaneous and central-peritoneal adipose depots in lean, obese and obese diabetic patients. We used CD31 to label the endothelial cells in order to evaluate the response of the vascular network to VEGF synthesis. Our results showed an increase of VEGF protein synthesis in obese and obese-diabetic patients compared to lean subjects where the protein was absent. The positivity for VEGF in obese diabetic samples was observed in numerous structures from the adipose depots, both in the stromal vascular fraction--blood vessels and stromal cells--as well as in the cytoplasm of adipocytes. Positivity in the vascular wall was observed more frequently in areas of perivascular and intralobular fibrosis. Obese and diabetic patients showed similar incidence of CD31 immunoreactivity with lean subjects in both subcutaneous and peritoneal depots. In conclusion, human adipose depots show a different incidence of VEGF positive cells in relation with their disposal and the metabolic status. VEGF synthesis in visceral adipose tissue is inefficient being not followed by angiogenesis to counterbalance tissue hypoxia. We suggest that may be a pathogenic link between the degrees of intralobular fibrosis in adipose depots and VEGF expression.

Cerebrovasculoprotective effects of azilsartan medoxomil in diabetes.

PubMed

Abdelsaid, Mohammed; Coucha, Maha; Ergul, Adviye

2014-11-01

We have shown that Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes, develop significant cerebrovascular remodeling by the age of 18 weeks, which is characterized by increased media thickness and matrix deposition. Although early glycemic control prevents diabetes-mediated remodeling of the cerebrovasculature, whether the remodeling can be reversed is unknown. Given that angiotensin II type 1 receptor blockers reverse pathologic vascular remodeling and function independent of changes in blood pressure in other vascular beds, we hypothesized that azilsartan medoxomil, a new angiotensin II type 1 receptor blocker, is vasculoprotective by preventing and reversing cerebrovascular remodeling in diabetes. Control Wistar and diabetic GK rats (n = 6-8 per group) were treated with vehicle (water) or azilsartan medoxomil (3 mg/kg/d) from the age of 14 to 18 or 18 to 22 weeks before or after vascular remodeling is established, respectively. Blood glucose and blood pressure were monitored and middle cerebral artery structure and function were evaluated using pressurized arteriography. Blood glucose was higher in GK rats compared with Wistar rats. Azilsartan treatment lowered blood glucose in diabetic animals with no effect on blood pressure. Diabetic animals exhibited lower myogenic tone, increased wall thickness, and cross-sectional area compared with control group animals, which were corrected by azilsartan treatment when started at the onset of diabetes or later after vascular remodeling is established. Azilsartan medoxomil offers preventive and therapeutic vasculoprotection in diabetes-induced cerebrovascular remodeling and myogenic dysfunction and this is independent of blood pressure. Published by Elsevier Inc.

Influence of strut cross-section of stents on local hemodynamics in stented arteries

NASA Astrophysics Data System (ADS)

Jiang, Yongfei; Zhang, Jun; Zhao, Wanhua

2016-05-01

Stenting is a very effective treatment for stenotic vascular diseases, but vascular geometries altered by stent implantation may lead to flow disturbances which play an important role in the initiation and progression of restenosis, especially in the near wall in stented arterial regions. So stent designs have become one of the indispensable factors needed to be considered for reducing the flow disturbances. In this paper, the structural designs of strut cross-section are considered as an aspect of stent designs to be studied in details. Six virtual stents with different strut cross-section are designed for deployments in the same ideal arterial model. Computational fluid dynamics (CFD) methods are performed to study how the shape and the aspect ratio (AR) of strut cross-section modified the local hemodynamics in the stented segments. The results indicate that stents with different strut cross-sections have different influence on the hemodynamics. Stents with streamlined cross-sectional struts for circular arc or elliptical arc can significantly enhance wall shear stress (WSS) in the stented segments, and reduce the flow disturbances around stent struts. The performances of stents with streamlined cross-sectional struts are better than that of stents with non-streamlined cross-sectional struts for rectangle. The results also show that stents with a larger AR cross-section are more conductive to improve the blood flow. The present study provides an understanding of the flow physics in the vicinity of stent struts and indicates that the shape and AR of strut cross-section ought to be considered as important factors to minimize flow disturbance in stent designs.

Leaf traits in parental and hybrid species of Sorbus (Rosaceae).

PubMed

Durkovic, Jaroslav; Kardosová, Monika; Canová, Ingrid; Lagana, Rastislav; Priwitzer, Tibor; Chorvát, Dusan; Cicák, Alojz; Pichler, Viliam

2012-09-01

Knowledge of functional leaf traits can provide important insights into the processes structuring plant communities. In the genus Sorbus, the generation of taxonomic novelty through reticulate evolution that gives rise to new microspecies is believed to be driven primarily by a series of interspecific hybridizations among closely related taxa. We tested hypotheses for dispersion of intermediacy across the leaf traits in Sorbus hybrids and for trait linkages with leaf area and specific leaf area. Here, we measured and compared the whole complex of growth, vascular, and ecophysiological leaf traits among parental (Sorbus aria, Sorbus aucuparia, Sorbus chamaemespilus) and natural hybrid (Sorbus montisalpae, Sorbus zuzanae) species growing under field conditions. A recently developed atomic force microscopy technique, PeakForce quantitative nanomechanical mapping, was used to characterize the topography of cell wall surfaces of tracheary elements and to map the reduced Young's modulus of elasticity. Intermediacy was associated predominantly with leaf growth traits, whereas vascular and ecophysiological traits were mainly parental-like and transgressive phenotypes. Larger-leaf species tended to have lower modulus of elasticity values for midrib tracheary element cell walls. Leaves with a biomass investment related to a higher specific leaf area had a lower density. Leaf area- and length-normalized theoretical hydraulic conductivity was related to leaf thickness. For the whole complex of examined leaf traits, hybrid microspecies were mosaics of parental-like, intermediate, and transgressive phenotypes. The high proportion of transgressive character expressions found in Sorbus hybrids implies that generation of extreme traits through transgressive segregation played a key role in the speciation process.

Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature

NASA Astrophysics Data System (ADS)

Dai, Guohao; Kaazempur-Mofrad, Mohammad R.; Natarajan, Sripriya; Zhang, Yuzhi; Vaughn, Saran; Blackman, Brett R.; Kamm, Roger D.; García-Cardeña, Guillermo; Gimbrone, Michael A., Jr.

2004-10-01

Atherosclerotic lesion localization to regions of disturbed flow within certain arterial geometries, in humans and experimental animals, suggests an important role for local hemodynamic forces in atherogenesis. To explore how endothelial cells (EC) acquire functional/dysfunctional phenotypes in response to vascular region-specific flow patterns, we have used an in vitro dynamic flow system to accurately reproduce arterial shear stress waveforms on cultured human EC and have examined the effects on EC gene expression by using a high-throughput transcriptional profiling approach. The flow patterns in the carotid artery bifurcations of several normal human subjects were characterized by using 3D flow analysis based on actual vascular geometries and blood flow profiles. Two prototypic arterial waveforms, "athero-prone" and "athero-protective," were defined as representative of the wall shear stresses in two distinct regions of the carotid artery (carotid sinus and distal internal carotid artery) that are typically "susceptible" or "resistant," respectively, to atherosclerotic lesion development. These two waveforms were applied to cultured EC, and cDNA microarrays were used to analyze the differential patterns of EC gene expression. In addition, the differential effects of athero-prone vs. athero-protective waveforms were further characterized on several parameters of EC structure and function, including actin cytoskeletal organization, expression and localization of junctional proteins, activation of the NF-B transcriptional pathway, and expression of proinflammatory cytokines and adhesion molecules. These global gene expression patterns and functional data reveal a distinct phenotypic modulation in response to the wall shear stresses present in atherosclerosis-susceptible vs. atherosclerosis-resistant human arterial geometries.

Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

PubMed Central

Parastatidis, Ioannis; Weiss, Daiana; Joseph, Giji; Taylor, W Robert

2013-01-01

Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity. PMID:23950141

Circulating inhibitor of ouabain-insensitive cation transport in malignantrenal hypertension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simon, G.

1986-03-01

The role of circulating humoral agents in the pathogenesis of vascular wall Na depletion in malignant hypertension (MHT) was investigated. Plasma was collected from 33 male F344 rats with malignant one-kidney, one clip HT and 22 normotensive control rats. MHT developed spontaneously and was characterized by inactivity, weight loss, edema, anemia or hemoconcentration, hyperkalemia, and renal insufficiency. For bioassay, monolayers of quiescent vascular smooth muscle cells from F344 rats were incubated in deproteinized or whole plasma for measurement of /sup 86/Rb uptake with or without 2 mM ouabain or 1 mM furosemide. Compared to controls, ouabain-insensitive /sup 86/Rb uptake wasmore » reduced from 8.2 +- 2.0 nmol/mg protein min/sup -1/ (mean +- SD) to 5.2 +- 1.4 in deproteinized plasma (p < 0.01, N = 12) and from 6.6 +- 1.9 to 4.0 +- 0.3 in whole plasma (p < 0.05, N=5) of rats with MHT, due in part to a reduction in furosemide-sensitive uptake (p < 0.01, N = 6). There were no differences in ouabain-sensitive /sup 86/Rb uptake of cells between groups. In rats with MHT the increased Na content of the aorta that characterizes benign one-kidney, one clip HT was reversed, and bladder wall Na content was reduced (p < 0.001, N = 9). In MHT, a furosemide-like, ouabain-insensitive cation transport inhibitor in blood and urine may be the cause of vascular wall Na loss and of natriuresis that triggers the syndrome.« less

[Oxidative stress and vascular function].

PubMed

Urbański, Karol; Nowak, Michal; Guzik, Tomasz J

2013-01-01

The maintenance of blood vessel homeostasis is closely associated with Reactive Oxygen and Nitrogen Species (ROS and RNS) production in the blood vessel wall. The main molecules taking part in this process are nitric oxide (NO), superoxide anion (O2*-), hydrogen peroxide (H2O2) and their derivatives. The production of these factors occurs in health and disease, however the increased ROS release is often referred to as oxidative stress. While initially oxidative stress was considered systemically, recent data indicate that it occurs locally in subcellular spaces and may be a result of dysfunction of individual enzyme systems. Oxidative stress induces inflammation, proliferation and migration of vascular smooth muscle cells, may regulate apoptosis and the function of the cells of vascular wall, finally leading to dysfunction of endothelium, media and adventitia, leading to cardiovascular diseases such as atherosclerosis, hypertension or heart failure. It is believed that a family of NADPH oxidases is the main source of ROS in the vessel wall, but also in other organs and tissues. It consists of seven known and quite precisely characterized homologues (NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) which often have very distinct activity and cellular localization and function. Besides harmful actions, we are beginning to understand the protective effects of ROS and RNS. They have many functions regulating redox-sensitive gene expression and influencing a proper function of cells and vessels. NOX4 has been particularly well characterized in this respect. Thus, the maintenance of the right homeostasis depends not only on ROS removing capabilities, but especially on preserving the adequate level of ROS production.

In vivo high-resolution structural imaging of large arteries in small rodents using two-photon laser scanning microscopy

NASA Astrophysics Data System (ADS)

Megens, Remco T. A.; Reitsma, Sietze; Prinzen, Lenneke; Oude Egbrink, Mirjam G. A.; Engels, Wim; Leenders, Peter J. A.; Brunenberg, Ellen J. L.; Reesink, Koen D.; Janssen, Ben J. A.; Ter Haar Romeny, Bart M.; Slaaf, Dick W.; van Zandvoort, Marc A. M. J.

2010-01-01

In vivo (molecular) imaging of the vessel wall of large arteries at subcellular resolution is crucial for unraveling vascular pathophysiology. We previously showed the applicability of two-photon laser scanning microscopy (TPLSM) in mounted arteries ex vivo. However, in vivo TPLSM has thus far suffered from in-frame and between-frame motion artifacts due to arterial movement with cardiac and respiratory activity. Now, motion artifacts are suppressed by accelerated image acquisition triggered on cardiac and respiratory activity. In vivo TPLSM is performed on rat renal and mouse carotid arteries, both surgically exposed and labeled fluorescently (cell nuclei, elastin, and collagen). The use of short acquisition times consistently limit in-frame motion artifacts. Additionally, triggered imaging reduces between-frame artifacts. Indeed, structures in the vessel wall (cell nuclei, elastic laminae) can be imaged at subcellular resolution. In mechanically damaged carotid arteries, even the subendothelial collagen sheet (~1 μm) is visualized using collagen-targeted quantum dots. We demonstrate stable in vivo imaging of large arteries at subcellular resolution using TPLSM triggered on cardiac and respiratory cycles. This creates great opportunities for studying (diseased) arteries in vivo or immediate validation of in vivo molecular imaging techniques such as magnetic resonance imaging (MRI), ultrasound, and positron emission tomography (PET).

A simplified in vivo approach for evaluating the bioabsorbable behavior of candidate stent materials.

PubMed

Pierson, Daniel; Edick, Jacob; Tauscher, Aaron; Pokorney, Ellen; Bowen, Patrick; Gelbaugh, Jesse; Stinson, Jon; Getty, Heather; Lee, Chee Huei; Drelich, Jaroslaw; Goldman, Jeremy

2012-01-01

Metal stents are commonly used to revascularize occluded arteries. A bioabsorbable metal stent that harmlessly erodes away over time may minimize the normal chronic risks associated with permanent implants. However, there is no simple, low-cost method of introducing candidate materials into the arterial environment. Here, we developed a novel experimental model where a biomaterial wire is implanted into a rat artery lumen (simulating bioabsorbable stent blood contact) or artery wall (simulating bioabsorbable stent matrix contact). We use this model to clarify the corrosion mechanism of iron (≥99.5 wt %), which is a candidate bioabsorbable stent material due to its biocompatibility and mechanical strength. We found that iron wire encapsulation within the arterial wall extracellular matrix resulted in substantial biocorrosion by 22 days, with a voluminous corrosion product retained within the vessel wall at 9 months. In contrast, the blood-contacting luminal implant experienced minimal biocorrosion at 9 months. The importance of arterial blood versus arterial wall contact for regulating biocorrosion was confirmed with magnesium wires. We found that magnesium was highly corroded when placed in the arterial wall but was not corroded when exposed to blood in the arterial lumen for 3 weeks. The results demonstrate the capability of the vascular implantation model to conduct rapid in vivo assessments of vascular biomaterial corrosion behavior and to predict long-term biocorrosion behavior from material analyses. The results also highlight the critical role of the arterial environment (blood vs. matrix contact) in directing the corrosion behavior of biodegradable metals. Copyright © 2011 Wiley Periodicals, Inc.

Sulfated Hexasaccharides Attenuate Metastasis by Inhibition of P-selectin and Heparanase1

PubMed Central

Borsig, Lubor; Vlodavsky, Israel; Ishai-Michaeli, Rivka; Torri, Giangiacomo; Vismara, Elena

2011-01-01

Development of compounds that target both heparanase and selectins is emerging as a promising approach for cancer therapy. Selectins are vascular cell adhesion molecules that mediate tumor cell interactions with platelets, leukocytes, and the vascular endothelium. Heparanase is an endoglycosidase that degrades heparan sulfate in the tumor microenvironment, cell surfaces, and vessel wall. Acting together, these molecules facilitate tumor cell arrest, extravasation, and metastasis. Here, we report the preparation of novel semisynthetic sulfated tri mannose C-C-linked dimers (STMCs) endowed with heparanase and selectin inhibitory activity. The P-selectin specificity of the STMC was defined by the anomeric linkage of the C-C bond. This STMC hexasaccharide is an effective inhibitor of P-selectin in vivo. We show that selective inhibition of heparanase attenuates metastasis in B16-BL6 melanoma cells, expressing high levels of this endoglycosidase, but has no effect on the metastasis of MC-38 carcinoma cells that express little or no heparanase activity. P-selectin-specific STMC attenuated metastasis in both animal models, indicating that inhibition of tumor cell interaction with the vascular endothelium is critical for cancer dissemination. Thus, the small size, the stability of the C-C bond, and the chemically defined structure of the newly generated STMCs make them superior to heparin derivatives and signify STMCs as valuable candidates for further evaluation. PMID:21532885

Vascularization, High-Volume Solution Flow, and Localized Roles for Enzymes of Sucrose Metabolism during Tumorigenesis by Agrobacterium tumefaciens1

PubMed Central

Wächter, Rebecca; Langhans, Markus; Aloni, Roni; Götz, Simone; Weilmünster, Anke; Koops, Ariane; Temguia, Leopoldine; Mistrik, Igor; Pavlovkin, Jan; Rascher, Uwe; Schwalm, Katja; Koch, Karen E.; Ullrich, Cornelia I.

2003-01-01

Vascular differentiation and epidermal disruption are associated with establishment of tumors induced by Agrobacterium tumefaciens. Here, we address the relationship of these processes to the redirection of nutrient-bearing water flow and carbohydrate delivery for tumor growth within the castor bean (Ricinus communis) host. Treatment with aminoethoxyvinyl-glycine showed that vascular differentiation and epidermal disruption were central to ethylene-dependent tumor establishment. CO2 release paralleled tumor growth, but water flow increased dramatically during the first 3 weeks. However, tumor water loss contributed little to water flow to host shoots. Tumor water loss was followed by accumulation of the osmoprotectants, sucrose (Suc) and proline, in the tumor periphery, shifting hexose-to-Suc balance in favor of sugar signals for maturation and desiccation tolerance. Concurrent activities and sites of action for enzymes of Suc metabolism changed: Vacuolar invertase predominated during initial import of Suc into the symplastic continuum, corresponding to hexose concentrations in expanding tumors. Later, Suc synthase (SuSy) and cell wall invertase rose in the tumor periphery to modulate both Suc accumulation and descending turgor for import by metabolization. Sites of abscisic acid immunolocalization correlated with both central vacuolar invertase and peripheral cell wall invertase. Vascular roles were indicated by SuSy immunolocalization in xylem parenchyma for inorganic nutrient uptake and in phloem, where resolution allowed SuSy identification in sieve elements and companion cells, which has widespread implications for SuSy function in transport. Together, data indicate key roles for ethylene-dependent vascularization and cuticular disruption in the redirection of water flow and carbohydrate transport for successful tumor establishment. PMID:14526106

Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

PubMed

Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

2018-02-21

Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

PubMed

Welter, Michael; Rieger, Heiko

2013-01-01

Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various strategies to increase drug exposure time of tumor cells.

Role of the nicotinic acetylcholine receptor α3 subtype in vascular inflammation.

PubMed

Yang, Cui; Li, Zhengtao; Yan, Saimei; He, Yonghui; Dai, Rong; Leung, George Pek-Heng; Pan, Shitian; Yang, Jinyan; Yan, Rong; Du, Guanhua

2016-11-01

Vascular inflammation is a major factor contributing to the development of vascular diseases. The aim of this study was to investigate the role of the nicotinic acetylcholine receptor α3 subtype (α3-nAChR) in vascular inflammation. Vascular inflammation was studied in apolipoprotein E knockout (ApoE -/- ) mice fed a high-fat diet. Inflammatory markers were measured in mouse aortic endothelial cells (MAECs) and macrophages after α3-nAChRs were antagonized pharmacologically, or after the gene of α3-nAChRs was silenced. Treatment with α-conotoxin MII (MII; an α3-nAChR antagonist) increased the number of inflammatory cells infiltrating the aortic walls and further impaired the endothelium-dependent vasodilatations in the aorta of ApoE -/- mice. MII also increased the plasma levels of inflammatory cytokines. Furthermore, the infiltration of classical activated macrophages into the arterial wall of ApoE -/- mice was markedly elevated by MII but that of alternative activated macrophages was reduced. In MAECs, the lipopolysaccharide-stimulated secretion of adhesion molecules and inflammatory cytokines was enhanced by MII, or by silencing the gene of α3-nAChRs. This effect was reversed by inhibitors of the PI3K-Akt-IκKα/β-IκBα-NFκB pathways. In macrophages, the classical activation was enhanced, but the alternative activation was reduced when the gene of α3-nACh receptors was silenced. These effects were prevented by inhibitors of the IκKα/β-IκBα-NFκB and JAK2-STAT6-PPARγ pathways respectively. α3-nAChRs play a pivotal role in regulating the inflammatory responses in endothelial cells and macrophages. The mechanisms involve the modulations of multiple cell signalling pathways. © 2016 The British Pharmacological Society.

Role of Resident Stem Cells in Vessel Formation and Arteriosclerosis.

PubMed

Zhang, Li; Issa Bhaloo, Shirin; Chen, Ting; Zhou, Bin; Xu, Qingbo

2018-05-25

Vascular, resident stem cells are present in all 3 layers of the vessel wall; they play a role in vascular formation under physiological conditions and in remodeling in pathological situations. Throughout development and adult early life, resident stem cells participate in vessel formation through vasculogenesis and angiogenesis. In adults, the vascular stem cells are mostly quiescent in their niches but can be activated in response to injury and participate in endothelial repair and smooth muscle cell accumulation to form neointima. However, delineation of the characteristics and of the migration and differentiation behaviors of these stem cells is an area of ongoing investigation. A set of genetic mouse models for cell lineage tracing has been developed to specifically address the nature of these cells and both migration and differentiation processes during physiological angiogenesis and in vascular diseases. This review summarizes the current knowledge on resident stem cells, which has become more defined and refined in vascular biology research, thus contributing to the development of new potential therapeutic strategies to promote endothelial regeneration and ameliorate vascular disease development. © 2018 The Authors.

mTOR and vascular remodeling in lung diseases: current challenges and therapeutic prospects.

PubMed

Goncharova, Elena A

2013-05-01

Mammalian target of rapamycin (mTOR) is a major regulator of cellular metabolism, proliferation, and survival that is implicated in various proliferative and metabolic diseases, including obesity, type 2 diabetes, hamartoma syndromes, and cancer. Emerging evidence suggests a potential critical role of mTOR signaling in pulmonary vascular remodeling. Remodeling of small pulmonary arteries due to increased proliferation, resistance to apoptosis, and altered metabolism of cells forming the pulmonary vascular wall is a key currently irreversible pathological feature of pulmonary hypertension, a progressive pulmonary vascular disorder with high morbidity and mortality. In addition to rare familial and idiopathic forms, pulmonary hypertension is also a life-threatening complication of several lung diseases associated with hypoxia. This review aims to summarize our current knowledge and recent advances in understanding the role of the mTOR pathway in pulmonary vascular remodeling, with a specific focus on the hypoxia component, a confirmed shared trigger of pulmonary hypertension in lung diseases. We also discuss the emerging role of mTOR as a promising therapeutic target and mTOR inhibitors as potential pharmacological approaches to treat pulmonary vascular remodeling in pulmonary hypertension.

Beyond the G-spot: clitourethrovaginal complex anatomy in female orgasm.

PubMed

Jannini, Emmanuele A; Buisson, Odile; Rubio-Casillas, Alberto

2014-09-01

The search for the legendary, highly erogenous vaginal region, the Gräfenberg spot (G-spot), has produced important data, substantially improving understanding of the complex anatomy and physiology of sexual responses in women. Modern imaging techniques have enabled visualization of dynamic interactions of female genitals during self-sexual stimulation or coitus. Although no single structure consistent with a distinct G-spot has been identified, the vagina is not a passive organ but a highly dynamic structure with an active role in sexual arousal and intercourse. The anatomical relationships and dynamic interactions between the clitoris, urethra, and anterior vaginal wall have led to the concept of a clitourethrovaginal (CUV) complex, defining a variable, multifaceted morphofunctional area that, when properly stimulated during penetration, could induce orgasmic responses. Knowledge of the anatomy and physiology of the CUV complex might help to avoid damage to its neural, muscular, and vascular components during urological and gynaecological surgical procedures.

[Bone metabolism and cardiovascular function Update. Vascular calcification as a manifestation of bone-vascular axis].

PubMed

Kurabayashi, Masahiko

2014-07-01

Vascular calcification is the major cause of cardiovascular morbidity and mortality in the patients with type 2 diabetes, chronic kidney disease and in aging patients. Regardless of the morphology and location, most evidence indicates that vascular calcification involves an organized process recapitulating many cellular and molecular events that govern skeletal bone formation. While the large body of evidence that osteoblastic and osteochondrocytic cells contribute to vascular calcification, it remains unclear how osteoclasts are differentiated from their precursors and how osteoclasts play a role in calcium reabsorption in calcifying arteries. It is reassuring that calcium paradox is not merely due to the calcium shift from bone to artery wall, but is likely due to the differential response of both osteoblasts and osteoclasts to oxidative stress between bone and artery. To date, many studies have highlighted the important role for RANK/RANKL/OPG axis as unifying theme for the apparently opposite regulation of calcification between two tissues.

Vascular calcification: When should we interfere in chronic kidney disease patients and how?

PubMed Central

Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

2016-01-01

Chronic kidney disease (CKD) patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifications affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho deficiency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, promotes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic inflammation and vascular calcification is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular calcification and the different medications and medical procedures that can help to prolong the survival of CKD patients. PMID:27648404

Vascular-targeted nanocarriers: design considerations and strategies for successful treatment of atherosclerosis and other vascular diseases.

PubMed

Kelley, William J; Safari, Hanieh; Lopez-Cazares, Genesis; Eniola-Adefeso, Omolola

2016-11-01

Vascular-targeted nanocarriers are an attractive option for the treatment of a number of cardiovascular diseases, as they allow for more specific delivery and increased efficacy of many small molecule drugs. However, immune clearance, limited cellular uptake, and particle-cell dynamics in blood flow can hinder nanocarrier efficacy in many applications. This review aims to investigate successful strategies for the use of vascular-targeted nanocarriers in the treatment of cardiovascular diseases such as atherosclerosis. In particular, the review will highlight strategies employed for actively targeting the components of the atherosclerotic plaque, including endothelial cells, macrophages, and platelets and passive targeting via endothelial permeability, as well as design specifications (such as size, shape, and density) aimed at enhancing the ability of nanocarriers to reach the vascular wall. WIREs Nanomed Nanobiotechnol 2016, 8:909-926. doi: 10.1002/wnan.1414 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall

PubMed Central

Liu, Xiaoping; El-Mahdy, Mohamed A.; Boslett, James; Varadharaj, Saradhadevi; Hemann, Craig; Abdelghany, Tamer M.; Ismail, Raed S.; Little, Sean C.; Zhou, Danlei; Thuy, Le Thi Thanh; Kawada, Norifumi; Zweier, Jay L.

2017-01-01

The identity of the specific nitric oxide dioxygenase (NOD) that serves as the main in vivo regulator of O2-dependent NO degradation in smooth muscle remains elusive. Cytoglobin (Cygb) is a recently discovered globin expressed in fibroblasts and smooth muscle cells with unknown function. Cygb, coupled with a cellular reducing system, efficiently regulates the rate of NO consumption by metabolizing NO in an O2-dependent manner with decreased NO consumption in physiological hypoxia. Here we show that Cygb is a major regulator of NO degradation and cardiovascular tone. Knockout of Cygb greatly prolongs NO decay, increases vascular relaxation, and lowers blood pressure and systemic vascular resistance. We further demonstrate that downregulation of Cygb prevents angiotensin-mediated hypertension. Thus, Cygb has a critical role in the regulation of vascular tone and disease. We suggest that modulation of the expression and NOD activity of Cygb represents a strategy for the treatment of cardiovascular disease. PMID:28393874

Open Problems in Computational Vascular Biomechanics: Hemodynamics and Arterial Wall Mechanics

PubMed Central

Taylor, C.A.; Humphrey, J.D.

2009-01-01

The vasculature consists of a complex network of vessels ranging from large arteries to arterioles, capillaries, venules, and veins. This network is vital for the supply of oxygen and nutrients to tissues and the removal of carbon dioxide and waste products from tissues. Because of its primary role as a pressure-driven chemomechanical transport system, it should not be surprising that mechanics plays a vital role in the development and maintenance of the normal vasculature as well as in the progression and treatment of vascular disease. This review highlights some past successes of vascular biomechanics, but emphasizes the need for research that synthesizes complementary advances in molecular biology, biomechanics, medical imaging, computational methods, and computing power for purposes of increasing our understanding of vascular physiology and pathophysiology as well as improving the design of medical devices and clinical interventions, including surgical procedures. That is, computational mechanics has great promise to contribute to the continued improvement of vascular health. PMID:20161129

Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall

NASA Astrophysics Data System (ADS)

Liu, Xiaoping; El-Mahdy, Mohamed A.; Boslett, James; Varadharaj, Saradhadevi; Hemann, Craig; Abdelghany, Tamer M.; Ismail, Raed S.; Little, Sean C.; Zhou, Danlei; Thuy, Le Thi Thanh; Kawada, Norifumi; Zweier, Jay L.

2017-04-01

The identity of the specific nitric oxide dioxygenase (NOD) that serves as the main in vivo regulator of O2-dependent NO degradation in smooth muscle remains elusive. Cytoglobin (Cygb) is a recently discovered globin expressed in fibroblasts and smooth muscle cells with unknown function. Cygb, coupled with a cellular reducing system, efficiently regulates the rate of NO consumption by metabolizing NO in an O2-dependent manner with decreased NO consumption in physiological hypoxia. Here we show that Cygb is a major regulator of NO degradation and cardiovascular tone. Knockout of Cygb greatly prolongs NO decay, increases vascular relaxation, and lowers blood pressure and systemic vascular resistance. We further demonstrate that downregulation of Cygb prevents angiotensin-mediated hypertension. Thus, Cygb has a critical role in the regulation of vascular tone and disease. We suggest that modulation of the expression and NOD activity of Cygb represents a strategy for the treatment of cardiovascular disease.

Arterial wall histology in chronic pulsatile-flow and continuous-flow device circulatory support.

PubMed

Potapov, Evgenij V; Dranishnikov, Nikolay; Morawietz, Lars; Stepanenko, Alexander; Rezai, Sajjad; Blechschmidt, Cristiane; Lehmkuhl, Hans B; Weng, Yuguo; Pasic, Miralem; Hübler, Michael; Hetzer, Roland; Krabatsch, Thomas

2012-11-01

Continuous-flow (CF) ventricular assist devices (VAD) are an established option for treatment of end-stage heart failure. However, the effect of long-term CF with lack of peripheral arterial wall motions on blood pressure regulation and end-organ arterial wall sclerosis, especially in the case of long-term support (> 3 years), remains unclear. Tissue samples obtained at autopsy from liver, kidney, coronary arteries, and brain from 27 VAD recipients supported for > 180 days between 2000 and 2010 were histologically examined to assess vascular alterations, including perivascular infiltrate, intravascular infiltrate, wall thickness, thrombosis, endothelial cell swelling, vessel wall necrosis, and peri-vascular fibrosis. Pulsatile-flow (PF) devices had been inserted in 9 patients and CF devices had been inserted in 16. The pathologist was blinded to the group distribution. Demographic, pharmacologic, and clinical data were retrospectively analyzed before surgery and during the follow-up period of up to 24 months. Median duration of support was 467 days (range, 235-1,588 days) in the PF group and 263 days (range, 182-942 days) in the CF group. Demographic and clinical data before and after surgery were similar. Amiodarone was more often used during follow-up in CF group than in the PF group (61% vs 10%, p = 0.009). Throughout the follow-up period, mean arterial pressure did not differ between recipients of the 2 pump types, nor did systolic and diastolic pressure, except at 2 weeks after VAD implantation, when systolic blood pressure was higher (p = 0.05) and diastolic lower (p = 0.03) in the PF group. Histologic studies did not identify any relevant differences in arterial wall characteristics between the 2 groups. Long-term mechanical circulatory support with CF devices does not adversely influence arterial wall properties of the end-organ vasculature. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Endoplasmic reticulum stress inhibition reduces hypertension through the preservation of resistance blood vessel structure and function.

PubMed

Carlisle, Rachel E; Werner, Kaitlyn E; Yum, Victoria; Lu, Chao; Tat, Victor; Memon, Muzammil; No, Yejin; Ask, Kjetil; Dickhout, Jeffrey G

2016-08-01

Our purpose was to determine if endoplasmic reticulum stress inhibition lowers blood pressure (BP) in hypertension by correcting vascular dysfunction. The spontaneously hypertensive rat (SHR) was used as a model of human essential hypertension with its normotensive control, the Wistar Kyoto rat. Animals were subjected to endoplasmic reticulum stress inhibition with 4-phenylbutyric acid (4-PBA; 1 g/kg per day, orally) for 5 weeks from 12 weeks of age. BP was measured weekly noninvasively and at endpoint with carotid arterial cannulation. Small mesenteric arteries were removed for vascular studies. Function was assessed with a Mulvany-Halpern style myograph, and structure was assessed by measurement of medial-to-lumen ratio in perfusion fixed vessels as well as three-dimensional confocal reconstruction of vessel wall components. Endoplasmic reticulum stress was assessed by quantitative real time-PCR and western blotting; oxidative stress was assessed by 3-nitrotyrosine and dihydroethidium staining. 4-PBA significantly lowered BP in SHR (vehicle 206.1 ± 4.3 vs. 4-PBA 178.9 ± 3.1, systolic) but not Wistar Kyoto. 4-PBA diminished contractility and augmented endothelial-dependent vasodilation in SHR small mesenteric arteries, as well as reducing media-to-lumen ratio. 4-PBA significantly reduced endoplasmic reticulum stress in SHR resistance vessels. Normotensive resistance vessels, treated with the endoplasmic reticulum stress-inducing agent, tunicamycin, show decreased endothelial-dependent vasodilation; this was improved with 4-PBA treatment. 3-Nitrotyrosine and dihydroethidium staining indicated that endoplasmic reticulum stress leads to reactive oxygen species generation resolvable by 4-PBA treatment. Endoplasmic reticulum stress caused endothelial-mediated vascular dysfunction contributing to elevated BP in the SHR model of human essential hypertension.

Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

PubMed Central

Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

2016-01-01

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth muscle cells, assayed by measuring intracellular collagen content. We observed increased intracellular levels of ascorbate under supplementation with elevated doses of ascorbic acid, as well as its lipid soluble derivative ascorbyl palmitate. Nifedipine reduced ascorbic acid intracellular influx in cultured aortic smooth muscle cells with nifedipine (50 µM) compared to control. Adverse effects of nifedipine were neutralized either by an increased level of cell supplementation with ascorbic acid or by substituting it with ascorbyl palmitate. These studies suggest that adverse effects of channel blockers could be caused by their weakening the arterial wall integrity by interfering with proper extracellular matrix formation. In conclusion, these studies confirm the adverse effects of channel blockers on collagen type l and lV deposition, the key ECM components essential for maintaining optimal structural integrity of the arterial walls. Ascorbate supplementation reversed channel blocker inhibition of these collagen types synthesis and deposition. The results of this study imply the benefits of ascorbate and ascorbate palmitate supplementation in medical management of cardiovascular disease in order to compensate for adverse effects of channel blockers. PMID:27335688

Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

PubMed

Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

2016-01-01

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth muscle cells, assayed by measuring intracellular collagen content. We observed increased intracellular levels of ascorbate under supplementation with elevated doses of ascorbic acid, as well as its lipid soluble derivative ascorbyl palmitate. Nifedipine reduced ascorbic acid intracellular influx in cultured aortic smooth muscle cells with nifedipine (50 µM) compared to control. Adverse effects of nifedipine were neutralized either by an increased level of cell supplementation with ascorbic acid or by substituting it with ascorbyl palmitate. These studies suggest that adverse effects of channel blockers could be caused by their weakening the arterial wall integrity by interfering with proper extracellular matrix formation. In conclusion, these studies confirm the adverse effects of channel blockers on collagen type l and lV deposition, the key ECM components essential for maintaining optimal structural integrity of the arterial walls. Ascorbate supplementation reversed channel blocker inhibition of these collagen types synthesis and deposition. The results of this study imply the benefits of ascorbate and ascorbate palmitate supplementation in medical management of cardiovascular disease in order to compensate for adverse effects of channel blockers.

Endoscopic digital holography for measuring flows in opaque vessels

NASA Astrophysics Data System (ADS)

Arévalo, Laura; Palero, Virginia; Lobera, Julia; Arroyo, M. Pilar

2012-10-01

In this work a new application of digital holography for the study of cardio vascular diseases is proposed. The simultaneous measurement of the blood flow velocity and the vein wall deformation can be obtained by combining digital holography and endoscopy. Endoscopes are used for the illumination and recording of digital holograms inside a vein model. Two different endoscopes have been used in different vein models in order to test the technique performance. Preliminary results of flow velocity and wall deformation are presented.

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

PubMed

Kurabayashi, Masahiko

2015-05-01

Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

Protein glycation, diabetes, and aging.

PubMed

Ulrich, P; Cerami, A

2001-01-01

Biological amines react with reducing sugars to form a complex family of rearranged and dehydrated covalent adducts that are often yellow-brown and/or fluorescent and include many cross-linked structures. Food chemists have long studied this process as a source of flavor, color, and texture changes in cooked, processed, and stored foods. During the 1970s and 1980s, it was realized that this process, called the Maillard reaction or advanced glycation, also occurs slowly in vivo. Advanced glycation endproducts (AGEs) that form are implicated, causing the complications of diabetes and aging, primarily via adventitious and crosslinking of proteins. Long-lived proteins such as structural collagen and lens crystallins particularly are implicated as pathogenic targets of AGE processes. AGE formation in vascular wall collagen appears to be an especially deleterious event, causing crosslinking of collagen molecules to each other and to circulating proteins. This leads to plaque formation, basement membrane thickening, and loss of vascular elasticity. The chemistry of these later-stage, glycation-derived crosslinks is still incompletely understood but, based on the hypothesis that AGE formation involves reactive carbonyl groups, the authors introduced the carbonyl reagent aminoguanidine hydrochloride as an inhibitor of AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers have shown the effectiveness of aminoguanidine in slowing or preventing a wide range of complications of diabetes and aging in animals and, recently, in humans. Since, the authors have developed a new class of agents, exemplified by 4,5-dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already-formed AGE protein-protein crosslinks. These agents are based on a new theory of AGE crosslinking that postulates that alpha-dicarbonyl structures are present in AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown to be capable of reverting indices of vascular compliance to levels seen in younger animals. Human clinical trials are underway.

Scanning electron microscopy observation of vascularization around hydroxyapatite using vascular corrosion casts.

PubMed

Chang, C S; Su, C Y; Lin, T C

1999-01-01

An intimate relationship exists between the regenerative response of the vascular and osseous elements following hydroxyapatite (HA) implantation. In order to fully comprehend the 3-dimensional vascular architecture around HA, dense HA particles were implanted into the tibiae of dogs. Following healing periods of 2 weeks, 1 month, and 3 months, the tibiae were prepared by the corrosion cast technique. Under scanning electron microscopy (SEM) observation, the characteristic vascular morphology of the HA-implanted cavity was successfully demonstrated. The initial vascularization began in the form of loose sinusoidal capillaries. Many sinusoids formed a complex network by anastomosing with each other. The newly formed vessels extended centripetally from the peripheral cavity wall and from the periosteal surface. Under greater magnification, the tapered vascular sprouting was shown to project into the space that was previously occupied by an HA particle. The presence of vascular sprouting is clearly an important indicator of angiogenesis. Increasing vascularization was demonstrated with time. The presence of vessels in the Haversian's canal indicated the more established vascularization. Almost full vascularization of the HA-implanted cavity was seen 3 months after implantation. The vascular organizational layout of the cavity was also clearly shown in the fractured transverse-sectioned sample. In the control without HA implantation, the central region of the cavity showed a hollow pattern in the initial stage. The vascularization looked like it was collapsing and not fully filling the cavity. However, remarkable differences of the final vascular pattern could not be found between the study and control group after 3-month implantation. The study provides the time-lapsed 3-dimensional vascular changes of the HA-implanted cavity, as well as the value of the corrosion cast technique in examining the bony circulation. Copyright 1999 John Wiley & Sons, Inc.

Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers

PubMed Central

Zhou, Qiu-Lan; Chen, Zhi-Yi; Yang, Feng

2014-01-01

With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers. PMID:25202710

Bioactive nanocomposite for chest-wall replacement: Cellular response in a murine model.

PubMed

Jungraithmayr, Wolfgang; Laube, Isabelle; Hild, Nora; Stark, Wendelin J; Mihic-Probst, Daniela; Weder, Walter; Buschmann, Johanna

2014-07-01

Chest-wall invading malignancies usually necessitate the resection of the respective part of the thoracic wall. Gore-Tex® is the material of choice that is traditionally used to repair thoracic defects. This material is well accepted by the recipient; however, though not rejected, it is an inert material and behaves like a 'foreign body' within the thoracic wall. By contrast, there are materials that have the potential to physiologically integrate into the host, and these materials are currently under in vitro and also in vivo investigation. These materials offer a gradual but complete biodegradation over time, and severe adverse inflammatory responses can be avoided. Here, we present a novel material that is a biodegradable nanocomposite based on poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles in comparison to the traditionally employed Gore-Tex® being the standard for chest-wall replacement. On a mouse model of thoracic wall resection, that resembles the technique and localization applied in humans, poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles and Gore-Tex® were implanted subcutaneously and additionally tested in a separate series as a chest-wall graft. After 1, 2, 4 and 8 weeks cell infiltration into the respective materials, inflammatory reactions as well as neo-vascularization (endothelial cells) were determined in six different zones. While Gore-Tex® allowed for cell infiltration only at the outer surface, electrospun poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles were completely penetrated by infiltrating cells. These cells were composed mainly by macrophages, with only 4% of giant cells and lymphocytes. Total macrophage count increased by time while the number of IL1-β-expressing macrophages decreased, indicating a protective state towards the graft. As such, poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles seem to develop ideal characteristics as a material for chest-wall replacement by (a) having the advantage of full biodegradation, (b) displaying stable chest-wall structures and (c) adapting a physiological and integrating graft compared to Gore-Tex®. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Diabetic cardiomyopathy: Where are we 40 years later?

PubMed Central

Sharma, Vijay; McNeill, John H

2006-01-01

Diabetic cardiomyopathy is a cardiac disease that arises as a result of the diabetic state, independent of vascular or valvular pathology. It manifests initially as asymptomatic diastolic dysfunction, which progresses to symptomatic heart failure. The compliance of the heart wall is decreased and contractile function is impaired. The pathophysiology is incompletely understood, but appears to be initiated both by hyperglycemia and changes in cardiac metabolism. These changes induce oxidative stress and activate a number of secondary messenger pathways, leading to cardiac hypertrophy, fibrosis and cell death. Alterations in contractile proteins and intracellular ions impair excitation-contraction coupling, while decreased autonomic responsiveness and autonomic neuropathy impair its regulation. Extensive structural abnormalities also occur, which have deleterious mechanical and functional consequences. PMID:16568154

Hydroxycinnamic acid-derived polymers constitute the polyaromatic domain of suberin

NASA Technical Reports Server (NTRS)

Bernards, M. A.; Lopez, M. L.; Zajicek, J.; Lewis, N. G.

1995-01-01

Suberin is an abundant, complex, intractable, plant cell wall polymeric network that forms both protective and wound-healing layers. Its function is, therefore, critical to the survival of all vascular plants. Its chemical structure and biosynthesis are poorly defined, although it is known to consist of both aromatic and aliphatic domains. While the composition of the aliphatic component has been fairly well characterized, that of the phenolic component has not. Using a combination of specific carbon-13 labeling techniques, and in situ solid state 13C NMR spectroscopic analysis, we now provide the first direct evidence for the nature of the phenolic domain of suberin and report here that it is almost exclusively comprised of a covalently linked, hydroxycinnamic acid-derived polymeric matrix.

Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

PubMed

Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

2017-08-17

Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

Nitrogen fertilizer application affects lodging resistance by altering secondary cell wall synthesis in japonica rice (Oryza sativa).

PubMed

Zhang, Wujun; Wu, Longmei; Ding, Yanfeng; Yao, Xiong; Wu, Xiaoran; Weng, Fei; Li, Ganghua; Liu, Zhenghui; Tang, She; Ding, Chengqiang; Wang, Shaohua

2017-09-01

Stem mechanical strength is an important agricultural quantitative trait that is closely related to lodging resistance in rice, which is known to be reduced by fertilizer with higher levels of nitrogen. To understand the mechanism that regulates stem mechanical strength in response to nitrogen, we analysed stem morphology, anatomy, mechanical properties, cell wall components, and expression of cell wall-related genes, in two varieties of japonica rice, namely, Wuyunjing23 (lodging-resistant variety) and W3668 (lodging-susceptible variety). The results showed that higher nitrogen fertilizer increased the lodging index in both varieties due to a reduction in breaking strength and bending stress, and these changes were larger in W3668. Cellulose content decreased slightly under higher nitrogen fertilizer, whereas lignin content reduced remarkably. Histochemical staining revealed that high nitrogen application decreased lignin deposition in the secondary cell wall of the sclerenchyma cells and vascular bundle cells compared with the low nitrogen treatments, while it did not alter the pattern of cellulose deposition in these cells in both Wuyunjing23 and W3668. In addition, the expression of the genes involved in lignin biosynthesis, OsPAL, OsCoMT, Os4CL3, OsCCR, OsCAD2, OsCAD7, OsCesA4, and OsCesA7, were also down-regulated under higher nitrogen conditions at the early stage of culm growth. These results suggest that the genes involved in lignin biosynthesis are down-regulated by higher nitrogen fertilizer, which causes lignin deficiency in the secondary cell walls and the weakening of mechanical tissue structure. Subsequently, this results in these internodes with reduced mechanical strength and poor lodging resistance.

Heterogeneous mechanics of the mouse pulmonary arterial network.

PubMed

Lee, Pilhwa; Carlson, Brian E; Chesler, Naomi; Olufsen, Mette S; Qureshi, M Umar; Smith, Nicolas P; Sochi, Taha; Beard, Daniel A

2016-10-01

Individualized modeling and simulation of blood flow mechanics find applications in both animal research and patient care. Individual animal or patient models for blood vessel mechanics are based on combining measured vascular geometry with a fluid structure model coupling formulations describing dynamics of the fluid and mechanics of the wall. For example, one-dimensional fluid flow modeling requires a constitutive law relating vessel cross-sectional deformation to pressure in the lumen. To investigate means of identifying appropriate constitutive relationships, an automated segmentation algorithm was applied to micro-computerized tomography images from a mouse lung obtained at four different static pressures to identify the static pressure-radius relationship for four generations of vessels in the pulmonary arterial network. A shape-fitting function was parameterized for each vessel in the network to characterize the nonlinear and heterogeneous nature of vessel distensibility in the pulmonary arteries. These data on morphometric and mechanical properties were used to simulate pressure and flow velocity propagation in the network using one-dimensional representations of fluid and vessel wall mechanics. Moreover, wave intensity analysis was used to study effects of wall mechanics on generation and propagation of pressure wave reflections. Simulations were conducted to investigate the role of linear versus nonlinear formulations of wall elasticity and homogeneous versus heterogeneous treatments of vessel wall properties. Accounting for heterogeneity, by parameterizing the pressure/distention equation of state individually for each vessel segment, was found to have little effect on the predicted pressure profiles and wave propagation compared to a homogeneous parameterization based on average behavior. However, substantially different results were obtained using a linear elastic thin-shell model than were obtained using a nonlinear model that has a more physiologically realistic pressure versus radius relationship.

Very low protein diets supplemented with keto-analogues in ESRD predialysis patients and its effect on vascular stiffness and AVF Maturation.

PubMed

David, Cristiana; Peride, Ileana; Niculae, Andrei; Constantin, Alexandra Maria; Checherita, Ionel Alexandru

2016-09-20

Native arteriovenous fistula (AVF) is the most appropriate type of vascular access for chronic dialysis. Its patency rates depend on vascular wall characteristics. Ketoacid analogues of essential amino acids (KA/EAA) are prescribed in end-stage renal disease (ESRD) pre-dialysis patients to lower toxic metabolic products generation and improve nutritional status. We hypothesized that very-low protein diet (VLPD) supplemented with KA/EAA may influence arterial wall stiffness and affect AVF maturation rates and duration in pre-dialysis ESRD patients. In a prospective, cohort, 3 years study we enrolled 67 consecutive non-diabetic early referral ESRD patients that underwent AVF creation in our hospital. Patients were divided in two groups based on their regimen 12 months prior to surgery: a VLPD supplemented with KA/EAA study group versus a low protein diet non-KA/EAA-supplemented control group. For each patient we performed serum analysis for the parameters of bone mineral disease, inflammation and nutritional status, one pulse wave velocity (PWV) measurement and one Doppler ultrasound (US) determination prior the surgery, followed by consequent Doppler US assessments at 4, 6, 8 and 12 weeks after it. Rates and duration of mature AVF achievement were noted. We used logistic regression to analyze the association between AVF maturation and KA/EAA administration, by comparing rates and durations between groups, unadjusted and adjusted for systolic blood pressure, C-reactive protein, PWV, phosphorus values. All parameters in the logistic model were transformed in binary variables. A p-value < α = 0.05 was considered significant; data were processed using SPSS 16 software and Excel. In the study group (n = 28, aged 57 ± 12.35, 13 females) we registered better serum phosphate (p = 0.022) and C-reactive protein control (p = 0.021), lower PWV (p = 0.007) and a higher percent of AVF creation success (33.3 % versus 17.8 %, p < 0.05). AVF maturation duration was lower in study group (5.91 versus 7.15 weeks, p < 0.001). VLPD supplemented with KA/EAA appear to improve the native AVF primary outcome, decreasing the initial vascular stiffness, possible by preserving vascular wall quality in CKD patients through a better serum phosphate levels control and the limitation of inflammatory response.

High-resolution confocal imaging of wall ingrowth deposition in plant transfer cells: Semi-quantitative analysis of phloem parenchyma transfer cell development in leaf minor veins of Arabidopsis.

PubMed

Nguyen, Suong T T; McCurdy, David W

2015-04-23

Transfer cells (TCs) are trans-differentiated versions of existing cell types designed to facilitate enhanced membrane transport of nutrients at symplasmic/apoplasmic interfaces. This transport capacity is conferred by intricate wall ingrowths deposited secondarily on the inner face of the primary cell wall, hence promoting the potential trans-membrane flux of solutes and consequently assigning TCs as having key roles in plant growth and productivity. However, TCs are typically positioned deep within tissues and have been studied mostly by electron microscopy. Recent advances in fluorophore labelling of plant cell walls using a modified pseudo-Schiff-propidium iodide (mPS-PI) staining procedure in combination with high-resolution confocal microscopy have allowed visualization of cellular details of individual tissue layers in whole mounts, hence enabling study of tissue and cellular architecture without the need for tissue sectioning. Here we apply a simplified version of the mPS-PI procedure for confocal imaging of cellulose-enriched wall ingrowths in vascular TCs at the whole tissue level. The simplified mPS-PI staining procedure produced high-resolution three-dimensional images of individual cell types in vascular bundles and, importantly, wall ingrowths in phloem parenchyma (PP) TCs in minor veins of Arabidopsis leaves and companion cell TCs in pea. More efficient staining of tissues was obtained by replacing complex clearing procedures with a simple post-fixation bleaching step. We used this modified procedure to survey the presence of PP TCs in other tissues of Arabidopsis including cotyledons, cauline leaves and sepals. This high-resolution imaging enabled us to classify different stages of wall ingrowth development in Arabidopsis leaves, hence enabling semi-quantitative assessment of the extent of wall ingrowth deposition in PP TCs at the whole leaf level. Finally, we conducted a defoliation experiment as an example of using this approach to statistically analyze responses of PP TC development to leaf ablation. Use of a modified mPS-PI staining technique resulted in high-resolution confocal imaging of polarized wall ingrowth deposition in TCs. This technique can be used in place of conventional electron microscopy and opens new possibilities to study mechanisms determining polarized deposition of wall ingrowths and use reverse genetics to identify regulatory genes controlling TC trans-differentiation.

Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo.

PubMed

Massberg, Steffen; Konrad, Ildiko; Bültmann, Andreas; Schulz, Christian; Münch, Götz; Peluso, Mario; Lorenz, Michael; Schneider, Simon; Besta, Felicitas; Müller, Iris; Hu, Bin; Langer, Harald; Kremmer, Elisabeth; Rudelius, Martina; Heinzmann, Ulrich; Ungerer, Martin; Gawaz, Meinrad

2004-02-01

Platelet-collagen interactions play a fundamental role in the process of arterial thrombosis. The major platelet collagen receptor is the glycoprotein VI (GPVI). Here, we determined the effects of a soluble dimeric form of GPVI on platelet adhesion in vitro and in vivo. We fused the extracellular domain of GPVI with the human immunoglobulin Fc domain. The soluble dimeric form of GPVI (GPVI-Fc) specifically bound to immobilized collagen. Binding of GPVI-Fc to collagen was inhibited competitively by soluble GPVI-Fc, but not control Fc lacking the external GPVI domain. GPVI-Fc inhibited the adhesion of CHO cells that stably express human GPVI and of platelets on collagen and attenuated thrombus formation under shear conditions in vitro. To test the effects of GPVI-Fc in vivo, arterial thrombosis was induced in the mouse carotid artery, and platelet-vessel wall interactions were visualized by intravital fluorescence microscopy. Infusion of GPVI-Fc but not of control Fc virtually abolished stable arrest and aggregation of platelets following vascular injury. Importantly, GPVI-Fc but not control Fc, was detected at areas of vascular injury. These findings further substantiate the critical role of the collagen receptor GPVI in the initiation of thrombus formation at sites of vascular injury and identify soluble GPVI as a promising antithrombotic strategy.

A study of hearing function and histopathologic changes in the cochlea of the type 2 diabetes model Tsumura Suzuki obese diabetes mouse.

PubMed

Tsuda, Junko; Sugahara, Kazuma; Hori, Takeshi; Kanagawa, Eiju; Takaki, Eiichi; Fujimoto, Mitsuaki; Nakai, Akira; Yamashita, Hiroshi

2016-11-01

This study used Tsumura Suzuki Obese Diabetes (TSOD) mice as a spontaneous type 2 diabetes model and Tsumura Suzuki Non-obesity (TSNO) mice as controls to investigate factors involved in the onset of hearing impairment. Body weight, blood glucose levels, and auditory brainstem responses (ABRs) were measured. The cochleae were excised and evaluated histopathologically. The TSOD mice showed significant hyperglycemia at 2-7 months and severe obesity at 5-10 months; significantly elevated ABR thresholds at 8-10 months; and the capillary lumens in the cochlea stria vascularis were narrower in the TSOD mice than in the TSNO mice. At 17 months, India ink vascular staining of the TSOD mice's cochleae revealed decreased capillary density in the stria vascularis. The vascular area of capillaries in the stria vascularis and the vascular area were significantly smaller in TSOD mice. Histopathological analysis showed vessel wall thickening in the modiolus and narrowed capillaries in the stria vascularis, suggesting reduced blood flow to the inner ear. The diabetes mice model used in our study showed early age-associated hearing loss, and histopathology showed findings of vessel wall thickening in the modiolus, narrowing of capillaries in the stria vascularis, and chronically reduced blood flow in the cochlea.

Hematopoiesis Primer Modeling Combined Injury

DTIC Science & Technology

2012-05-01

wall (Nachman and Rafii 2008). With thrombocytopenia, vascular permeability increases allowing local movement of erythrocytes into the tissue which...Gottingen minipigs, humans, and other large animal models. PLoS One. 2011; 6(9):e25210. Epub 2011 Sep 28. Nachman R.L., S. Rafii . Platelets, petechiae

Shading Contributes to the Reduction of Stem Mechanical Strength by Decreasing Cell Wall Synthesis in Japonica Rice (Oryza sativa L.).

PubMed

Wu, Longmei; Zhang, Wujun; Ding, Yanfeng; Zhang, Jianwei; Cambula, Elidio D; Weng, Fei; Liu, Zhenghui; Ding, Chengqiang; Tang, She; Chen, Lin; Wang, Shaohua; Li, Ganghua

2017-01-01

Low solar radiation caused by industrial development and solar dimming has become a limitation in crop production in China. It is widely accepted that low solar radiation influences many aspects of plant development, including slender, weak stems and susceptibility to lodging. However, the underlying mechanisms are not well understood. To clarify how low solar radiation affects stem mechanical strength formation and lodging resistance, the japonica rice cultivars Wuyunjing23 (lodging-resistant) and W3668 (lodging-susceptible) were grown under field conditions with normal light (Control) and shading (the incident light was reduced by 60%) with a black nylon net. The yield and yield components, plant morphological characteristics, the stem mechanical strength, cell wall components, culm microstructure, gene expression correlated with cellulose and lignin biosynthesis were measured. The results showed that shading significantly reduced grain yield attributed to reduction of spikelets per panicles and grain weight. The stem-breaking strength decreased significantly under shading treatment; consequently, resulting in higher lodging index in rice plant in both varieties, as revealed by decreased by culm diameter, culm wall thickness and increased plant height, gravity center height. Compared with control, cell wall components including non-structural carbohydrate, sucrose, cellulose, and lignin reduced quite higher. With histochemical straining, shading largely reduced lignin deposition in the sclerenchyma cells and vascular bundle cells compared with control, and decreased cellulose deposition in the parenchyma cells of culm tissue in both Wuyunjing23 and W3668. And under shading condition, gene expression involved in secondary cell wall synthesis, OsPAL, OsCOMT, OsCCoAOMT, OsCCR , and OsCAD2 , and primary cell wall synthesis, OsCesA1, OsCesA3 , and OsCesA8 were decreased significantly. These results suggest that gene expression involved in the reduction of lignin and cellulose in both sclerenchyma and parenchyma cells, which attribute to lignin and cellulose in culm tissue and weak mechanical tissue, consequently, result in poor stem strength and higher lodging risks. Highlights : (1) Shading decreases the stem mechanical strength of japonica rice by decreasing non-structural carbohydrate, sucrose, lignin, and cellulose accumulation in culms. (2) The decrease of carbon source under shading condition is the cause for the lower lignin and cellulose accumulation in culm. (3) The expression of genes involved in lignin and primarily cell wall cellulose biosynthesis ( OsCesA1, OsCesA3 , and OsCesA8 ) at the stem formation stage are down-regulated under shading condition, inducing defective cell wall development and poor lodging resistance.

Lifelong Cyclic Mechanical Strain Promotes Large Elastic Artery Stiffening: Increased Pulse Pressure and Old Age-Related Organ Failure.

PubMed

Thorin-Trescases, Nathalie; Thorin, Eric

2016-05-01

The arterial wall is under a huge mechanical constraint imposed by the cardiac cycle that is bound to generate damage with time. Each heartbeat indeed imposes a pulsatile pressure that generates a vascular stretch. Lifetime accumulation of pulsatile stretches will eventually induce fatigue of the elastic large arterial walls, such as aortic and carotid artery walls, promoting their stiffening that will gradually perturb the normal blood flow and local pressure within the organs, and lead to organ failure. The augmented pulse pressure induced by arterial stiffening favours left ventricular hypertrophy because of the repeated extra work against stiff high-pressure arteries, and tissue damage as a result of excessive pulsatile pressure transmitted into the microcirculation, especially in low resistance/high-flow organs such as the brain and kidneys. Vascular aging is therefore characterized by the stiffening of large elastic arteries leading to a gradual increase in pulse pressure with age. In this review we focus on the effect of age-related stiffening of large elastic arteries. We report the clinical evidence linking arterial stiffness and organ failure and discuss the molecular pathways that are activated by the increase of mechanical stress in the wall. We also discuss the possible interventions that could limit arterial stiffening with age, such as regular aerobic exercise training, and some pharmacological approaches. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease.

PubMed

Nörenberg, Dominik; Ebersberger, Hans U; Diederichs, Gerd; Hamm, Bernd; Botnar, René M; Makowski, Marcus R

2016-03-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Wall-to-lumen ratio of intracranial arteries measured by indocyanine green angiography

PubMed Central

Nakagawa, Daichi; Shojima, Masaaki; Yoshino, Masanori; Kin, Taichi; Imai, Hideaki; Nomura, Seiji; Saito, Toki; Nakatomi, Hirofumi; Oyama, Hiroshi; Saito, Nobuhito

2016-01-01

Background: The wall-to-lumen ratio (WLR) is an important parameter in vascular medicine because it indicates the character of vascular wall as well as the degree of stenosis. Despite the advances in medical imaging technologies, it is still difficult to measure the thin-walled normal intracranial arteries, and the reports on the WLR of normal intracranial artery are limited. It might be possible to calculate the WLR using the indocyanine green (ICG) angiography, which is used to observe intracranial vessels during microsurgery. Purpose: To evaluate the WLR of normal intracranial arteries using ICG angiography. Materials and Methods: From the three cases in which ICG angiography was recorded with a ruler during microsurgery, 20 measurement points were chosen for the analysis. The ICG was injected intravenously with a dose of 0.2 mg/kg, and the vessels were inspected at high magnification using an operating microscope equipped with near-infrared illumination system. The vessel outer diameter and the luminal diameter were measured using the images before and after the ICG arrival based on the pixel ratio method using a ruler as reference, respectively. The WLR was calculated as 0.5 × (vessel outer diameter − vessel luminal diameter). Results: The WLR (mean ± standard deviation) of normal intracranial arteries was 0.086 ± 0.022. The WLR tended to be high in small arteries. Conclusion: The WLR of normal intracranial arteries calculated using ICG angiography was consistent with the WLR reported in the previous reports based on human autopsy. PMID:27695538

Accelerated whole brain intracranial vessel wall imaging using black blood fast spin echo with compressed sensing (CS-SPACE).

PubMed

Zhu, Chengcheng; Tian, Bing; Chen, Luguang; Eisenmenger, Laura; Raithel, Esther; Forman, Christoph; Ahn, Sinyeob; Laub, Gerhard; Liu, Qi; Lu, Jianping; Liu, Jing; Hess, Christopher; Saloner, David

2018-06-01

Develop and optimize an accelerated, high-resolution (0.5 mm isotropic) 3D black blood MRI technique to reduce scan time for whole-brain intracranial vessel wall imaging. A 3D accelerated T 1 -weighted fast-spin-echo prototype sequence using compressed sensing (CS-SPACE) was developed at 3T. Both the acquisition [echo train length (ETL), under-sampling factor] and reconstruction parameters (regularization parameter, number of iterations) were first optimized in 5 healthy volunteers. Ten patients with a variety of intracranial vascular disease presentations (aneurysm, atherosclerosis, dissection, vasculitis) were imaged with SPACE and optimized CS-SPACE, pre and post Gd contrast. Lumen/wall area, wall-to-lumen contrast ratio (CR), enhancement ratio (ER), sharpness, and qualitative scores (1-4) by two radiologists were recorded. The optimized CS-SPACE protocol has ETL 60, 20% k-space under-sampling, 0.002 regularization factor with 20 iterations. In patient studies, CS-SPACE and conventional SPACE had comparable image scores both pre- (3.35 ± 0.85 vs. 3.54 ± 0.65, p = 0.13) and post-contrast (3.72 ± 0.58 vs. 3.53 ± 0.57, p = 0.15), but the CS-SPACE acquisition was 37% faster (6:48 vs. 10:50). CS-SPACE agreed with SPACE for lumen/wall area, ER measurements and sharpness, but marginally reduced the CR. In the evaluation of intracranial vascular disease, CS-SPACE provides a substantial reduction in scan time compared to conventional T 1 -weighted SPACE while maintaining good image quality.

Extraglandular and intraglandular vascularization of canine prostate.

PubMed

Stefanov, Miroslav

2004-03-01

The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism. Copyright 2004 Wiley-Liss, Inc.

Sucrose-Metabolizing Enzymes in Transport Tissues and Adjacent Sink Structures in Developing Citrus Fruit 1

PubMed Central

Lowell, Cadance A.; Tomlinson, Patricia T.; Koch, Karen E.

1989-01-01

Juice tissues of citrus lack phloem; therefore, photosynthates enroute to juice sacs exit the vascular system on the surface of each segment. Areas of extensive phloem unloading and transport (vascular bundles + segment epidermis) can thus be separated from those of assimilate storage (juice sacs) and adjacent tissues where both processes occur (peel). Sugar composition, dry weight accumulation, and activities of four sucrose-metabolizing enzymes (soluble and cell-wall-bound acid invertase, alkaline invertase, sucrose synthase, and sucrose phosphate synthase) were measured in these transport and sink tissues of grapefruit (Citrus paradisi Macf.) to determine more clearly whether a given enzyme appeared to be more directly associated with assimilate transport versus deposition or utilization. Results were compared at three developmental stages. Activity of sucrose (per gram fresh weight and per milligram protein) extracted from zones of extensive phloem unloading and transport was significantly greater than from adjacent sink tissues during the stages (II and III) when juice sacs grow most rapidly. In stage II fruit, activity of sucrose synthase also significantly surpassed that of all other sucrose-metabolizing enzymes in extracts from the transport tissues (vascular bundles + segment epidermis). In contrast, sucrose phosphate synthase and alkaline invertase at this stage of growth were the most active enzymes from adjacent, rapidly growing, phloem-free sink tissues (juice sacs). Activity of these two enzymes in extracts from juice sacs was significantly greater than that form the transport tissues (vascular bundles + segment epidermis). Soluble acid invertase was the most active enzyme in extracts from all tissues of very young fruit (stage I), including nonvascular regions, but nearly disappeared prior to the onset of juice sac sugar accumulation. The physiological function of high sucrose synthase activity in the transport tissues during rapid sucrose import remains to be determined. PMID:16666942

Computer-aided design of microvasculature systems for use in vascular scaffold production.

PubMed

Mondy, William Lafayette; Cameron, Don; Timmermans, Jean-Pierre; De Clerck, Nora; Sasov, Alexander; Casteleyn, Christophe; Piegl, Les A

2009-09-01

In vitro biomedical engineering of intact, functional vascular networks, which include capillary structures, is a prerequisite for adequate vascular scaffold production. Capillary structures are necessary since they provide the elements and compounds for the growth, function and maintenance of 3D tissue structures. Computer-aided modeling of stereolithographic (STL) micro-computer tomographic (micro-CT) 3D models is a technique that enables us to mimic the design of vascular tree systems containing capillary beds, found in tissues. In our first paper (Mondy et al 2009 Tissue Eng. at press), using micro-CT, we studied the possibility of using vascular tissues to produce data capable of aiding the design of vascular tree scaffolding, which would help in the reverse engineering of a complete vascular tree system including capillary bed structures. In this paper, we used STL models of large datasets of computer-aided design (CAD) data of vascular structures which contained capillary structures that mimic those in the dermal layers of rabbit skin. Using CAD software we created from 3D STL models a bio-CAD design for the development of capillary-containing vascular tree scaffolding for skin. This method is designed to enhance a variety of therapeutic protocols including, but not limited to, organ and tissue repair, systemic disease mediation and cell/tissue transplantation therapy. Our successful approach to in vitro vasculogenesis will allow the bioengineering of various other types of 3D tissue structures, and as such greatly expands the potential applications of biomedical engineering technology into the fields of biomedical research and medicine.

Physical activity measured by accelerometry and its associations with cardiac structure and vascular function in young and middle-aged adults.

PubMed

Andersson, Charlotte; Lyass, Asya; Larson, Martin G; Spartano, Nicole L; Vita, Joseph A; Benjamin, Emelia J; Murabito, Joanne M; Esliger, Dale W; Blease, Susan J; Hamburg, Naomi M; Mitchell, Gary F; Vasan, Ramachandran S

2015-03-19

Physical activity is associated with several health benefits, including lower cardiovascular disease risk. The independent influence of physical activity on cardiac and vascular function in the community, however, has been sparsely investigated. We related objective measures of moderate- to vigorous-intensity physical activity (MVPA, assessed by accelerometry) to cardiac and vascular indices in 2376 participants of the Framingham Heart Study third generation cohort (54% women, mean age 47 years). Using multivariable regression models, we related MVPA to the following echocardiographic and vascular measures: left ventricular mass, left atrial and aortic root sizes, carotid-femoral pulse wave velocity, augmentation index, and forward pressure wave. Men and women engaged in MVPA 29.9±21.4 and 25.5±19.4 min/day, respectively. Higher values of MVPA (per 10-minute increment) were associated with lower carotid-femoral pulse wave velocity (estimate -0.53 ms/m; P=0.006) and lower forward pressure wave (estimate -0.23 mm Hg; P=0.03) but were not associated with augmentation index (estimate 0.13%; P=0.25). MVPA was associated positively with log(e) left ventricular mass (estimate 0.006 log(e) [g/m(2)]; P=0.0003), left ventricular wall thickness (estimate 0.07 mm; P=0.0001), and left atrial dimension (estimate 0.10 mm; P=0.01). MVPA also tended to be positively associated with aortic root dimension (estimate 0.05 mm; P=0.052). Associations of MVPA with cardiovascular measures were similar, in general, for bouts lasting <10 versus ≥10 minutes. In our community-based sample, greater physical activity was associated with lower vascular stiffness but with higher echocardiographic left ventricular mass and left atrial size. These findings suggest complex relations of usual levels of physical activity and cardiovascular remodeling. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Ferulic acid combined with astragaloside IV protects against vascular endothelial dysfunction in diabetic rats.

PubMed

Yin, Yonghui; Qi, Fanghua; Song, Zhenhua; Zhang, Bo; Teng, Jialin

2014-08-01

Dysfunction of the endothelium is regarded as an important factor in the pathogenesis of vascular disease in diabetes mellitus (DM). Unfortunately, prevention of the progression of vascular complications of DM remains pessimistic. Ferulic acid and astragaloside IV, isolated from traditional Chinese medicine Angelica sinensis and Radix astragali respectively, exhibit potential cardio-protective and anti-hyperglycemic properties. In the present study, we investigated the protective effects and underlying mechanism of ferulic acid and astragaloside IV against vascular endothelial dysfunction in diabetic rats. After the diabetic rat model was established using streptozotocin, sixty rats were divided into 6 groups (control, model, ferulic acid, astragaloside IV, ferulic acid + astragaloside IV, and metformin) and treated for 10 weeks. Blood samples were collected to measure levels of hemoglobin A1c (HbAlc), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), low density lipoproteins (Ox-LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine (Cr), nitric oxide (NO) and endothelial nitric oxide synthase (eNOS), and abdominal aorta tissue samples were collected for observing histological morphology changes of endothelium and detecting gene and protein expression of nuclear factor-κB (NF-κB) P65, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α). We found that ferulic acid combined with astragaloside IV was capable of improving the structure of the aortic endothelium wall, attenuating the increase of HbAlc, TG, TC, LDL-C and Ox-LDL, promoting the release of NO and eNOS, and inhibiting over-activation of MCP-1, TNF-α, and NF-κB P65, without damage to liver and kidney function. In conclusion, ferulic acid combined with astragaloside IV exhibited significant protective effects against vascular endothelial dysfunction in diabetic rats through the NF-κB pathway involving decrease of Ox-LDL, increase of NO and eNOS, and activation of NF-κB P65, MCP-1 and TNF-α.

Single-Walled Carbon Nanotubes Induce Pulmonary and Vascular Response Following Intratracheal Instillation

EPA Science Inventory

Carbon-based nanotubes have been shown to induce varying degrees of pulmonary response in rodents influenced by the dose, the extent of agglomeration, the chemistry of the suspension solution, and the functional properties. We hypothesized that low concentrations of non-modified ...

45 CFR 675.3 - Medical clearance criteria.

Code of Federal Regulations, 2012 CFR

2012-10-01

... following major organ systems: (1) Lungs and chest wall. (2) Heart and vascular system. (3) Abdominal organs and gastrointestinal system. (4) Endocrine or metabolic system. (5) Genitalia and urinary system. (6) Musculoskeletal. (7) Skin and cellular tissues. (8) Neurological Disorders. (9) Psychiatric or psychological. (10...

Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes congenital heart disease.

PubMed

Rhee, Siyeon; Chung, Jae I; King, Devin A; D'amato, Gaetano; Paik, David T; Duan, Anna; Chang, Andrew; Nagelberg, Danielle; Sharma, Bikram; Jeong, Youngtae; Diehn, Maximilian; Wu, Joseph C; Morrison, Ashby J; Red-Horse, Kristy

2018-01-25

During development, the formation of a mature, well-functioning heart requires transformation of the ventricular wall from a loose trabecular network into a dense compact myocardium at mid-gestation. Failure to compact is associated in humans with congenital diseases such as left ventricular non-compaction (LVNC). The mechanisms regulating myocardial compaction are however still poorly understood. Here, we show that deletion of the Ino80 chromatin remodeler in vascular endothelial cells prevents ventricular compaction in the developing mouse heart. This correlates with defective coronary vascularization, and specific deletion of Ino80 in the two major coronary progenitor tissues-sinus venosus and endocardium-causes intermediate phenotypes. In vitro, endothelial cells promote myocardial expansion independently of blood flow in an Ino80-dependent manner. Ino80 deletion increases the expression of E2F-activated genes and endothelial cell S-phase occupancy. Thus, Ino80 is essential for coronary angiogenesis and allows coronary vessels to support proper compaction of the heart wall.

Direct visualization of the arterial wall water permeability barrier using CARS microscopy

PubMed Central

Lucotte, Bertrand M.; Powell, Chloe; Knutson, Jay R.; Combs, Christian A.; Malide, Daniela; Yu, Zu-Xi; Knepper, Mark; Patel, Keval D.; Pielach, Anna; Johnson, Errin; Borysova, Lyudmyla; Balaban, Robert S.

2017-01-01

The artery wall is equipped with a water permeation barrier that allows blood to flow at high pressure without significant water leak. The precise location of this barrier is unknown despite its importance in vascular function and its contribution to many vascular complications when it is compromised. Herein we map the water permeability in intact arteries, using coherent anti-Stokes Raman scattering (CARS) microscopy and isotopic perfusion experiments. Generation of the CARS signal is optimized for water imaging with broadband excitation. We identify the water permeation barrier as the endothelial basolateral membrane and show that the apical membrane is highly permeable. This is confirmed by the distribution of the AQP1 water channel within endothelial membranes. These results indicate that arterial pressure equilibrates within the endothelium and is transmitted to the supporting basement membrane and internal elastic lamina macromolecules with minimal deformation of the sensitive endothelial cell. Disruption of this pressure transmission could contribute to endothelial cell dysfunction in various pathologies. PMID:28373558

Expression of very low density lipoprotein receptor mRNA in circulating human monocytes: its up-regulation by hypoxia.

PubMed

Nakazato, K; Ishibashi, T; Nagata, K; Seino, Y; Wada, Y; Sakamoto, T; Matsuoka, R; Teramoto, T; Sekimata, M; Homma, Y; Maruyama, Y

2001-04-01

Although very low density lipoprotein (VLDL) receptor expression by macrophages has been shown in the vascular wall, it is not clear whether or not circulating monocytes express the VLDL receptor. We investigated the expression of VLDL receptor mRNA in human peripheral blood monocytes and monocyte-derived macrophages by reverse transcriptase polymerase chain reaction (RT-PCR) and nucleotide sequencing after subcloning of PCR product. VLDL receptor mRNA was detected both in peripheral blood monocytes and monocyte-derived macrophages. Expression of VLDL receptor mRNA was upregulated by hypoxia in monocytes, whereas treatment with oxidized LDL, interleukin-1beta or monocyte chemoattractant protein-1 did not affect the levels of VLDL receptor mRNA in monocytes and macrophages. The present study shows a novel response of VLDL receptor mRNA to hypoxia, suggesting a role for VLDL receptor in the metabolism of lipoproteins in the vascular wall and the development of atherosclerosis.

Segmentation of Dilated Hemorrhoidal Veins in Hemorrhoidal Disease.

PubMed

Díaz-Flores, Lucio; Gutiérrez, Ricardo; González-Gómez, Miriam; García, Pino; Sáez, Francisco J; Díaz-Flores, Lucio; Carrasco, José Luis; Madrid, Juan F

2018-06-18

Vein segmentation is a vascular remodeling process mainly studied in experimental conditions and linked to hemodynamic factors, with clinical implications. The aim of this work is to assess the morphologic characteristics, associated findings, and mechanisms that participate in vein segmentation in humans. To this end, we examined 156 surgically obtained cases of hemorrhoidal disease. Segmentation occurred in 65 and was most prominent in 15, which were selected for serial sections, immunohistochemistry, and immunofluorescence procedures. The dilated veins showed differently sized spaces, separated by thin septa. Findings associated with vein segmentation were: (a) vascular channels formed from the vein intima endothelial cells (ECs) and located in the vein wall and/or intraluminal fibrin, (b) vascular loops formed by interconnected vascular channels (venous-venous connections), which encircled vein wall components or fibrin and formed folds/pillars/papillae (FPPs; the encircling ECs formed the FPP cover and the encircled components formed the core), and (c) FPP splitting, remodeling, alignment, and fusion, originating septa. Thrombosis was observed in some nonsegmented veins, while the segmented veins only occasionally contained thrombi. Dense microvasculature was also present in the interstitium and around veins. In conclusion, the findings suggest that hemorrhoidal vein segmentation is an adaptive process in which a piecemeal angiogenic mechanism participates, predominantly by intussusception, giving rise to intravascular FPPs, followed by linear rearrangement, remodeling and fusion of FPPs, and septa formation. Identification of other markers, as well as the molecular bases, hemodynamic relevance, and possible therapeutic implications of vein segmentation in dilated hemorrhoidal veins require further studies. © 2018 S. Karger AG, Basel.

Challenges and limitations of patient-specific vascular phantom fabrication using 3D Polyjet printing.

PubMed

Ionita, Ciprian N; Mokin, Maxim; Varble, Nicole; Bednarek, Daniel R; Xiang, Jianping; Snyder, Kenneth V; Siddiqui, Adnan H; Levy, Elad I; Meng, Hui; Rudin, Stephen

2014-03-13

Additive manufacturing (3D printing) technology offers a great opportunity towards development of patient-specific vascular anatomic models, for medical device testing and physiological condition evaluation. However, the development process is not yet well established and there are various limitations depending on the printing materials, the technology and the printer resolution. Patient-specific neuro-vascular anatomy was acquired from computed tomography angiography and rotational digital subtraction angiography (DSA). The volumes were imported into a Vitrea 3D workstation (Vital Images Inc.) and the vascular lumen of various vessels and pathologies were segmented using a "marching cubes" algorithm. The results were exported as Stereo Lithographic (STL) files and were further processed by smoothing, trimming, and wall extrusion (to add a custom wall to the model). The models were printed using a Polyjet printer, Eden 260V (Objet-Stratasys). To verify the phantom geometry accuracy, the phantom was reimaged using rotational DSA, and the new data was compared with the initial patient data. The most challenging part of the phantom manufacturing was removal of support material. This aspect could be a serious hurdle in building very tortuous phantoms or small vessels. The accuracy of the printed models was very good: distance analysis showed average differences of 120 μm between the patient and the phantom reconstructed volume dimensions. Most errors were due to residual support material left in the lumen of the phantom. Despite the post-printing challenges experienced during the support cleaning, this technology could be a tremendous benefit to medical research such as in device development and testing.

Challenges and limitations of patient-specific vascular phantom fabrication using 3D Polyjet printing

NASA Astrophysics Data System (ADS)

Ionita, Ciprian N.; Mokin, Maxim; Varble, Nicole; Bednarek, Daniel R.; Xiang, Jianping; Snyder, Kenneth V.; Siddiqui, Adnan H.; Levy, Elad I.; Meng, Hui; Rudin, Stephen

2014-03-01

Additive manufacturing (3D printing) technology offers a great opportunity towards development of patient-specific vascular anatomic models, for medical device testing and physiological condition evaluation. However, the development process is not yet well established and there are various limitations depending on the printing materials, the technology and the printer resolution. Patient-specific neuro-vascular anatomy was acquired from computed tomography angiography and rotational digital subtraction angiography (DSA). The volumes were imported into a Vitrea 3D workstation (Vital Images Inc.) and the vascular lumen of various vessels and pathologies were segmented using a "marching cubes" algorithm. The results were exported as Stereo Lithographic (STL) files and were further processed by smoothing, trimming, and wall extrusion (to add a custom wall to the model). The models were printed using a Polyjet printer, Eden 260V (Objet-Stratasys). To verify the phantom geometry accuracy, the phantom was reimaged using rotational DSA, and the new data was compared with the initial patient data. The most challenging part of the phantom manufacturing was removal of support material. This aspect could be a serious hurdle in building very tortuous phantoms or small vessels. The accuracy of the printed models was very good: distance analysis showed average differences of 120 μm between the patient and the phantom reconstructed volume dimensions. Most errors were due to residual support material left in the lumen of the phantom. Despite the post-printing challenges experienced during the support cleaning, this technology could be a tremendous benefit to medical research such as in device development and testing.

Molecular Imaging of Activated Matrix Metalloproteinases in Vascular Remodeling

PubMed Central

Zhang, Jiasheng; Nie, Lei; Razavian, Mahmoud; Ahmed, Masood; Dobrucki, Lawrence W.; Asadi, Abolfazl; Edwards, D. Scott; Azure, Michael; Sinusas, Albert J.; Sadeghi, Mehran M.

2008-01-01

Background Matrix metalloproteinase (MMP) activation plays a key role in vascular remodeling. RP782 is a novel 111In –labeled tracer with specificity for activated MMPs. We hypothesized that RP782 can detect injury-induced vascular remodeling in vivo. Methods and Results Left common carotid artery injury was induced using a guide wire in apolipoprotein E-/- mice. Sham surgery was performed on the contralateral artery, which served as control for imaging experiments. Carotid wire injury led to significant hyperplasia and expansive remodeling over a period of 4 weeks. MMP activity detected by in-situ zymography, increased in response to injury and was maximal by 3-4 weeks after injury. RP782 (11.1 MBq) was injected intravenously to apolipoprotein E-/- mice at 1, 2, 3, and 4 weeks after left carotid injury. MicroSPECT imaging was performed at 2 hours and was followed by CT angiography to localize the carotid arteries. In vivo images revealed focal uptake of RP782 in the injured carotid artery at 2, 3 and 4 weeks. Increased tracer uptake in the injured artery was confirmed by quantitative autoradiography. Pretreatment with 50-fold excess non-labeled tracer significantly reduced RP782 uptake in injured carotids, demonstrating uptake specificity. Weekly changes in the vessel wall area closely paralleled and correlated with RP782 uptake (Spearman r=0.95, p=0.001). Conclusions Injury-induced MMP activation in the vessel wall can be detected by RP782 microSPECT/CT imaging in vivo. RP782 uptake tracks the hyperplastic process in vascular remodeling, and provides an opportunity to track the remodeling process in vivo. PMID:18936327

Different effects of isoflavones on vascular function in premenopausal and postmenopausal smokers and nonsmokers: NYMPH study.

PubMed

Hoshida, Shiro; Miki, Takashi; Nakagawa, Takafumi; Shinoda, Yukinori; Inoshiro, Nobuaki; Terada, Katsuhiko; Adachi, Takayoshi

2011-11-01

Isoflavone intake has been associated with a reduction in the risk of cardiovascular disease in postmenopausal women. The aim of the present study was to determine if the effects of isoflavones on vascular function differ between premenopausal and postmenopausal women and between women who smoke and those who do not. Women smokers and nonsmokers who consumed 50 mg of isoflavone/day as black soybean tea for a period of 2 months (n = 55, mean age 39) were enrolled in the present study. We examined endothelial function, which was assessed by the percent change in flow-mediated dilation (%FMD) and arterial wall stiffness using the cardio-ankle vascular index (CAVI), as well as by biochemical parameters of the blood. Neither premenopausal (p = 0.697) nor postmenopausal (p = 0.389) smokers experienced an increase in %FMD after daily consumption of isoflavones. However, both premenopausal (p = 0.004) and postmenopausal (p = 0.019) nonsmokers exhibited a marked elevation in %FMD. By contrast, isoflavone intake effectively reduced CAVI among both premenopausal smokers (p = 0.027) and nonsmokers (p = 0.013), but had no effect on CAVI among postmenopausal smokers (p = 0.169) or nonsmokers (p = 0.128). The women smokers and nonsmokers did not differ in age or %FMD at the time of enrollment in the study. Thus, isoflavones have different effects on vascular endothelial function and arterial wall stiffness in premenopausal and postmenopausal smokers and nonsmokers.

Heterogeneous histomorphology, yet homogeneous vascular smooth muscle cell dedifferentiation, characterize human aneurysm disease.

PubMed

Busch, Albert; Hartmann, Elena; Grimm, Caroline; Ergün, Süleyman; Kickuth, Ralph; Otto, Christoph; Kellersmann, Richard; Lorenz, Udo

2017-11-01

Abdominal aortic aneurysm (AAA) is a frequent, potentially life-threatening, disease that can only be treated by surgical means such as open surgery or endovascular repair. No alternative treatment is currently available, and despite expanding knowledge about the pathomechanism, clinical trials on medical aneurysm abrogation have led to inconclusive results. The heterogeneity of human AAA based on histologic examination is thereby generally neglected. In this study we aimed to further elucidate the role of these differences in aneurysm disease. Tissue samples from AAA and popliteal artery aneurysm patients were examined by histomorphologic analysis, immunohistochemistry, Western blot, and polymerase chain reaction. The results were correlated with clinical data such as aneurysm diameter and laboratory results. The morphology of human AAA vessel wall probes varies tremendously based on the grade of inflammation. This correlates with increasing intima/media thickness and upregulation of the vascular endothelial growth factor cascade but not with any clinical parameter or the aneurysm diameter. The phenotypic switch of vascular smooth muscle cells occurred regardless of the inflammatory state and expressional changes of the transcription factors Kruppel-like factor-4 and transforming growth factor-β lead to differential protein localization in aneurysmal compared with control arteries. These changes were in similar manner also observed in samples from popliteal artery aneurysms, which, however, showed a more homogenous phenotype. Heterogeneity of AAA vessel walls based on inflammatory morphology does not correlate with AAA diameter yet harbors specific implications for basic research and possible aneurysm detection. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets.

PubMed

Vosen, Sarah; Rieck, Sarah; Heidsieck, Alexandra; Mykhaylyk, Olga; Zimmermann, Katrin; Bloch, Wilhelm; Eberbeck, Dietmar; Plank, Christian; Gleich, Bernhard; Pfeifer, Alexander; Fleischmann, Bernd K; Wenzel, Daniela

2016-01-26

Cardiovascular disease is often caused by endothelial cell (EC) dysfunction and atherosclerotic plaque formation at predilection sites. Also surgical procedures of plaque removal cause irreversible damage to the EC layer, inducing impairment of vascular function and restenosis. In the current study we have examined a potentially curative approach by radially symmetric re-endothelialization of vessels after their mechanical denudation. For this purpose a combination of nanotechnology with gene and cell therapy was applied to site-specifically re-endothelialize and restore vascular function. We have used complexes of lentiviral vectors and magnetic nanoparticles (MNPs) to overexpress the vasoprotective gene endothelial nitric oxide synthase (eNOS) in ECs. The MNP-loaded and eNOS-overexpressing cells were magnetic, and by magnetic fields they could be positioned at the vascular wall in a radially symmetric fashion even under flow conditions. We demonstrate that the treated vessels displayed enhanced eNOS expression and activity. Moreover, isometric force measurements revealed that EC replacement with eNOS-overexpressing cells restored endothelial function after vascular injury in eNOS(-/-) mice ex and in vivo. Thus, the combination of MNP-based gene and cell therapy with custom-made magnetic fields enables circumferential re-endothelialization of vessels and improvement of vascular function.

Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration.

PubMed

Busch, Albert; Hoffjan, Sabine; Bergmann, Frauke; Hartung, Birgit; Jung, Helena; Hanel, Daniela; Tzschach, Andeas; Kadar, Janos; von Kodolitsch, Yskert; Germer, Christoph-Thomas; Trobisch, Heiner; Strasser, Erwin; Wildenauer, René

2016-08-03

The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations. 22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity. The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting.

Regulator of calcineurin 1 mediates pathological vascular wall remodeling

PubMed Central

Esteban, Vanesa; Méndez-Barbero, Nerea; Jesús Jiménez-Borreguero, Luis; Roqué, Mercè; Novensá, Laura; Belén García-Redondo, Ana; Salaices, Mercedes; Vila, Luis; Arbonés, María L.

2011-01-01

Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed >1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1−/− mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression. PMID:21930771

The receptor-like kinase AtVRLK1 regulates secondary cell wall thickening.

PubMed

Huang, Cheng; Zhang, Rui; Gui, Jinshan; Zhong, Yu; Li, Laigeng

2018-04-20

During the growth and development of land plants, some specialized cells, such as tracheary elements, undergo secondary cell wall thickening. Secondary cell walls contain additional lignin, compared with primary cell walls, thus providing mechanical strength and potentially improving defenses against pathogens. However, the molecular mechanisms that initiate wall thickening are unknown. In this study, we identified an Arabidopsis thaliana leucine-rich repeat receptor-like kinase, encoded by AtVRLK1 (Vascular-Related RLK 1), that is specifically expressed in cells undergoing secondary cell wall thickening. Suppression of AtVRLK1expression resulted in a range of phenotypes that included retarded early elongation of the inflorescence stem, shorter fibers, slower root growth, and shorter flower filaments. In contrast, upregulation of AtVRLK1 led to longer fiber cells, reduced secondary cell wall thickening in fiber and vessel cells, and defects in anther dehiscence. Molecular and cellular analyses showed that downregulation of AtVRLK1 promoted secondary cell wall thickening and upregulation of AtVRLK1 enhanced cell elongation and inhibited secondary cell wall thickening. We propose that AtVRLK1 functions as a signaling component in coordinating cell elongation and cell wall thickening during growth and development. {copyright, serif} 2018 American Society of Plant Biologists. All rights reserved.

Characterization of a cinnamoyl-CoA reductase 1 (CCR1) mutant in maize: effects on lignification, fibre development, and global gene expression

PubMed Central

Tamasloukht, Barek; Wong Quai Lam, Mary Sarah-Jane; Martinez, Yves; Tozo, Koffi; Barbier, Odile; Jourda, Cyril; Jauneau, Alain; Borderies, Gisèle; Balzergue, Sandrine; Renou, Jean-Pierre; Huguet, Stéphanie; Martinant, Jean Pierre; Tatout, Christophe; Lapierre, Catherine; Barrière, Yves; Goffner, Deborah; Pichon, Magalie

2011-01-01

Cinnamoyl-CoA reductase (CCR), which catalyses the first committed step of the lignin-specific branch of monolignol biosynthesis, has been extensively characterized in dicot species, but few data are available in monocots. By screening a Mu insertional mutant collection in maize, a mutant in the CCR1 gene was isolated named Zmccr1–. In this mutant, CCR1 gene expression is reduced to 31% of the residual wild-type level. Zmccr1– exhibited enhanced digestibility without compromising plant growth and development. Lignin analysis revealed a slight decrease in lignin content and significant changes in lignin structure. p-Hydroxyphenyl units were strongly decreased and the syringyl/guaiacyl ratio was slightly increased. At the cellular level, alterations in lignin deposition were mainly observed in the walls of the sclerenchymatic fibre cells surrounding the vascular bundles. These cell walls showed little to no staining with phloroglucinol. These histochemical changes were accompanied by an increase in sclerenchyma surface area and an alteration in cell shape. In keeping with this cell type-specific phenotype, transcriptomics performed at an early stage of plant development revealed the down-regulation of genes specifically associated with fibre wall formation. To the present authors’ knowledge, this is the first functional characterization of CCR1 in a grass species. PMID:21493812

Trains of Red Blood Cells in a bi-dimensional microflows

NASA Astrophysics Data System (ADS)

Viallat, Annie; Iss, Cecile; Held, Delphine; Badens, Catherine; Charrier, Anne; Helfer, Emmanuèle; CINaM Team; Dpt de Génétique Médicale Team

2017-11-01

In the vascular microcirculation RBC distribution is uneven in the direction normal to the blood flow, as first evidenced by the existence of a cell-free layer near the vessel wall. In addition, the most rigid cells such as white blood cells and platelets are known to segregate to the walls while flowing in wide channels. We use microfluidic bi-dimensional channels (60 µm wide, 8 µm high, 5 mm long) to explore the flow structure in RBC suspensions at several hematocrits, flow rates and RBC rigidities. We observe the dynamical formation of RBC clusters and their motion along the flow direction. We study healthy RBCs, RBCs stiffened with glutaraldehyde, mixture of healthy and stiffened RBCs and RBC from sickle cell patients. Initially dispersed healthy RBCs organize, while flowing along the channel, into series of parallel trains. The train length depends on RBC hematocrit and flow rate. Stiffened RBCs do not cluster and mainly display tumbling motion like rigid disks. They destabilize existing trains and are preferentially observed close to the walls. We compared our results to that observed in microcapillaries, where trains of RBCs entirely fill in width the microchannel. This work has been carried out thanks to the support of the A*MIDEX project (n° ANR-11-IDEX-0001-02) funding by the ''Investissements d'Avenir'' French Government program, ma,ged by ANR.

Computational replication of the patient-specific stenting procedure for coronary artery bifurcations: From OCT and CT imaging to structural and hemodynamics analyses.

PubMed

Chiastra, Claudio; Wu, Wei; Dickerhoff, Benjamin; Aleiou, Ali; Dubini, Gabriele; Otake, Hiromasa; Migliavacca, Francesco; LaDisa, John F

2016-07-26

The optimal stenting technique for coronary artery bifurcations is still debated. With additional advances computational simulations can soon be used to compare stent designs or strategies based on verified structural and hemodynamics results in order to identify the optimal solution for each individual's anatomy. In this study, patient-specific simulations of stent deployment were performed for 2 cases to replicate the complete procedure conducted by interventional cardiologists. Subsequent computational fluid dynamics (CFD) analyses were conducted to quantify hemodynamic quantities linked to restenosis. Patient-specific pre-operative models of coronary bifurcations were reconstructed from CT angiography and optical coherence tomography (OCT). Plaque location and composition were estimated from OCT and assigned to models, and structural simulations were performed in Abaqus. Artery geometries after virtual stent expansion of Xience Prime or Nobori stents created in SolidWorks were compared to post-operative geometry from OCT and CT before being extracted and used for CFD simulations in SimVascular. Inflow boundary conditions based on body surface area, and downstream vascular resistances and capacitances were applied at branches to mimic physiology. Artery geometries obtained after virtual expansion were in good agreement with those reconstructed from patient images. Quantitative comparison of the distance between reconstructed and post-stent geometries revealed a maximum difference in area of 20.4%. Adverse indices of wall shear stress were more pronounced for thicker Nobori stents in both patients. These findings verify structural analyses of stent expansion, introduce a workflow to combine software packages for solid and fluid mechanics analysis, and underscore important stent design features from prior idealized studies. The proposed approach may ultimately be useful in determining an optimal choice of stent and position for each patient. Copyright © 2015 Elsevier Ltd. All rights reserved.

Illumina microRNA profiles reveal the involvement of miR397a in Citrus adaptation to long-term boron toxicity via modulating secondary cell-wall biosynthesis.

PubMed

Huang, Jing-Hao; Qi, Yi-Ping; Wen, Shou-Xing; Guo, Peng; Chen, Xiao-Min; Chen, Li-Song

2016-03-10

The mechanisms underlying tolerance to B-toxicity in plants are still controversial. Our previous studies indicated that B-toxicity is mainly limited to leaves in Citrus and that alternations of cell-wall structure in vascular bundles are involved in tolerance to B-toxicity. Here, miRNAs and their expression patterns were first identified in B-treated Citrus sinensis (tolerant) and C. grandis (intolerant) leaves via high-throughput sequencing. Candidate miRNAs were then verified with molecular and anatomical approaches. The results showed that 51 miRNAs in C. grandis and 20 miRNAs in C. sinensis were differentially expressed after B-toxic treatment. MiR395a and miR397a were the most significantly up-regulated miRNAs in B-toxic C. grandis leaves, but both were down-regulated in B-toxic C. sinensis leaves. Four auxin response factor genes and two laccase (LAC) genes were confirmed through 5'-RACE to be real targets of miR160a and miR397a, respectively. Up-regulation of LAC4 resulted in secondary deposition of cell-wall polysaccharides in vessel elements of C. sinensis, whereas down-regulation of both LAC17 and LAC4, led to poorly developed vessel elements in C. grandis. Our findings demonstrated that miR397a plays a pivotal role in woody Citrus tolerance to B-toxicity by targeting LAC17 and LAC4, both of which are responsible for secondary cell-wall synthesis.

Chronic Treatment with Minoxidil Induces Elastic Fiber Neosynthesis and Functional Improvement in the Aorta of Aged Mice.

PubMed

Coquand-Gandit, Marion; Jacob, Marie-Paule; Fhayli, Wassim; Romero, Beatriz; Georgieva, Miglena; Bouillot, Stéphanie; Estève, Eric; Andrieu, Jean-Pierre; Brasseur, Sandrine; Bouyon, Sophie; Garcia-Honduvilla, Natalio; Huber, Philippe; Buján, Julia; Atanasova, Milena; Faury, Gilles

2017-06-01

Normal arterial aging processes involve vascular cell dysfunction associated with wall stiffening, the latter being due to progressive elastin and elastic fiber degradation, and elastin and collagen cross-linking by advanced glycation end products (AGEs). These processes progressively lead to cardiovascular dysfunction during aging. Elastin is only synthesized during late gestation and childhood, and further degradation occurring throughout adulthood cannot be physiologically compensated by replacement of altered material. However, the ATP-dependent K + channel opener minoxidil has been shown to stimulate elastin expression in vitro and in vivo in the aorta of young adult rats. Therefore, we have studied the effect of a 10-week chronic oral treatment with minoxidil (120 mg/L in drinking water) on the aortic structure and function in aged 24-month-old mice. Minoxidil treatment increased tropoelastin, fibulin-5, and lysyl-oxidase messenger RNA levels, reinduced a moderate expression of elastin, and lowered the levels of AGE-related molecules. This was accompanied by the formation of newly synthesized elastic fibers, which had diverse orientations in the wall. A decrease in the glycation capacity of aortic elastin was also produced by minoxidil treatment. The ascending aorta also underwent a minoxidil-induced increase in diameter and decrease in wall thickness, which partly reversed the age-associated thickening and returned the wall thickness value and strain-stress relation closer to those of younger adult animals. In conclusion, our results suggest that minoxidil presents an interesting potential for arterial remodeling in an antiaging perspective, even when treating already aged animals.

Transplantation of mesenchymal stem cells cultured on biomatrix support induces repairing of digestive tract defects, in animal model.

PubMed

Sîrbu-Boeţi, Mirela-Patricia; Chivu, Mihaela; Pâslaru, Liliana Livia; Efrimescu, C; Herlea, V; Pecheanu, C; Moldovan, Lucia; Dragomir, Laura; Bleotu, Coralia; Ciucur, Elena; Vidulescu, Cristina; Vasilescu, Mihaela; Boicea, Anişoara; Mănoiu, S; Ionescu, M I; Popescu, I

2009-01-01

Transplanted mesenchymal stem cells (MSCs) appear to play a significant role in adult tissue repair. The aim of this research was to obtain MSCs enriched, three dimensional (3D) patches for transplant, and to test their ability to induce repair of iatrogenic digestive tract defects in rats. MSCs were obtained from human and rat bone marrow, cultured in vitro, and seeded in a collagen-agarose scaffold, where they showed enhanced viability and proliferation. The phenotype of the cultured cells was representative for MSCs (CD105+, CD90+, and CD34-, CD45-, CD3-, CD14-). The 3D patch was obtained by laying the MSCs enriched collagen-agarose scaffold on a human or swine aortic fragment. After excision of small portions of the rat digestive tract, the 3D patches were sutured at the edge of the defect using micro-surgical techniques. The rats were sacrificed at time-points and the regeneration of the digestive wall was investigated by immunofluorescence, light and electron microscopy. The MSCs enriched 3D patches were biocompatible, biodegradable, and prompted the regeneration of the four layers of the stomach and intestine wall in rats. Human cells were identified in the rat regenerated digestive wall as a hallmark of the transplanted MSCs. For the first time we constructed 3D patches made of cultured bone marrow MSCs, embedded into a collagen-rich biomatrix, on vascular bio-material support, and transplanted them in order to repair iatrogenic digestive tract defects. The result was a complete repair with preservation of the four layered structure of the digestive wall.

Illumina microRNA profiles reveal the involvement of miR397a in Citrus adaptation to long-term boron toxicity via modulating secondary cell-wall biosynthesis

PubMed Central

Huang, Jing-Hao; Qi, Yi-Ping; Wen, Shou-Xing; Guo, Peng; Chen, Xiao-Min; Chen, Li-Song

2016-01-01

The mechanisms underlying tolerance to B-toxicity in plants are still controversial. Our previous studies indicated that B-toxicity is mainly limited to leaves in Citrus and that alternations of cell-wall structure in vascular bundles are involved in tolerance to B-toxicity. Here, miRNAs and their expression patterns were first identified in B-treated Citrus sinensis (tolerant) and C. grandis (intolerant) leaves via high-throughput sequencing. Candidate miRNAs were then verified with molecular and anatomical approaches. The results showed that 51 miRNAs in C. grandis and 20 miRNAs in C. sinensis were differentially expressed after B-toxic treatment. MiR395a and miR397a were the most significantly up-regulated miRNAs in B-toxic C. grandis leaves, but both were down-regulated in B-toxic C. sinensis leaves. Four auxin response factor genes and two laccase (LAC) genes were confirmed through 5′-RACE to be real targets of miR160a and miR397a, respectively. Up-regulation of LAC4 resulted in secondary deposition of cell-wall polysaccharides in vessel elements of C. sinensis, whereas down-regulation of both LAC17 and LAC4, led to poorly developed vessel elements in C. grandis. Our findings demonstrated that miR397a plays a pivotal role in woody Citrus tolerance to B-toxicity by targeting LAC17 and LAC4, both of which are responsible for secondary cell-wall synthesis. PMID:26962011

Hair Follicle-Derived Smooth Muscle Cells and Small Intestinal Submucosa for Engineering Mechanically Robust and Vasoreactive Vascular Media

PubMed Central

Peng, Hao-Fan; Liu, Jin Yu

2011-01-01

Our laboratory recently reported a new source of smooth muscle cells (SMCs) derived from hair follicle (HF) mesenchymal stem cells. HF-SMCs demonstrated high proliferation and clonogenic potential as well as contractile function. In this study, we aimed at engineering the vascular media using HF-SMCs and a natural biomaterial, namely small intestinal submucosa (SIS). Engineering functional vascular constructs required application of mechanical force, resulting in actin reorganization and cellular alignment. In turn, cell alignment was necessary for development of receptor- and nonreceptor-mediated contractility as soon as 24 h after cell seeding. Within 2 weeks in culture, the cells migrated into SIS and secreted collagen and elastin, the two major extracellular matrix components of the vessel wall. At 2 weeks, vascular reactivity increased significantly up to three- to fivefold and mechanical properties were similar to those of native ovine arteries. Taken together, our data demonstrate that the combination of HF-SMCs with SIS resulted in mechanically strong, biologically functional vascular media with potential for arterial implantation. PMID:21083418

The Stromal Vascular Fraction From Fat Tissue in the Treatment of Osteochondral Knee Defect: Case Report

PubMed Central

Salikhov, Ramil Z.; Masgutov, Ruslan F.; Chekunov, Mikhail A.; Tazetdinova, Leysan G.; Masgutova, Galina; Teplov, Oleg V.; Galimov, Damir; Plakseichuk, Yuri; Yagudin, Ramil; Pankov, Igor O.; Rizvanov, Albert

2018-01-01

In this study we applied autologous fat tissue stromal vascular fraction (SVF) cells in combination with microfracturing technique in a 36-year-old man with an osteochondral lesion of the medial femoral condyle 8 months after the injury. Cell material was generated by fat tissue liposuction from the anterior abdominal wall with subsequent extraction of the SVF and injected through a mini-arthrotomy portal with subsequent fibrin sealant fixation. The follow-up period was 2 years. Clinical score improved from 23 to 96 according to IKDC and from 10 to 90 according to EQ-VAS at 24 months follow-up. Magnetic resonance imaging (MRI) before the surgery revealed an osteochondral lesion with development of significant trabecular edema that remained unchanged for 6 months despite conservative treatment. MRI 1 and 2 years after the surgery showed the recovery of the damaged cartilage thickness with somewhat uneven structure and a decrease in the trabecular edema of the femoral condyle. The use of SVF cells with fibrin sealant fixation might be a promising approach in the treatment of osteochondral joint lesions. Further studies are required. PMID:29900170

Roles of Perivascular Adipose Tissue in the Pathogenesis of Atherosclerosis

PubMed Central

Tanaka, Kimie; Sata, Masataka

2018-01-01

Traditionally, it is believed that white adipose tissues serve as energy storage, heat insulation, and mechanical cushion, whereas non-shivering thermogenesis occurs in brown adipose tissue. Recent evidence revealed that adipose tissue secretes many types of cytokines, called as adipocytokines, which modulate glucose metabolism, lipid profile, appetite, fibrinolysis, blood pressure, and inflammation. Most of the arteries are surrounded by perivascular adipose tissue (PVAT). PVAT has been thought to be simply a structurally supportive tissue for vasculature. However, recent studies showed that PVAT influences vasodilation and vasocontraction, suggesting that PVAT regulates vascular tone and diameter. Adipocytokines secreted from PVAT appear to have direct access to the adjacent arterial wall by diffusion or via vasa vasorum. In fact, PVAT around atherosclerotic lesions and mechanically-injured arteries displayed inflammatory cytokine profiles, suggesting that PVAT functions to promote vascular lesion formation. Many clinical studies revealed that increased accumulation of epicardial adipose tissue (EAT), which surrounds coronary arteries, is associated with coronary artery disease. In this review article, we will summarize recent findings about potential roles of PVAT in the pathogenesis of atherosclerosis, particularly focusing on a series of basic and clinical studies from our laboratory. PMID:29487532

Morphological changes in the anterior segment of the Abyssinian cat eye with hereditary rod-cone degeneration.

PubMed

May, Chr Albrecht; Lütjen-Drecoll, Elke; Narfström, Kristina

2005-10-01

The purpose of this study was to investigate morphological changes of the anterior segment of the eye in Abyssinian cats with progressive rod-cone degeneration and to correlate them with blood flow data obtained in the same animals. Sections of the left eyes of six normal cats and of eight cats with different stages of hereditary retinal degeneration were prepared for transmission and scanning electron microscopy. Tangential and sagittal sections were also stained with antibodies against substance P, tyrosine hydroxylase, panneuronal marker PGP9.5, nitric oxide synthase, synaptophysin, and smooth muscle alpha-actin. In Abyssinian cats with hereditary rod-cone degeneration, significant changes were observed in the iris consisting of irregularities in the vascular wall of smaller arteries without changes in their innervation pattern. The ciliary processes were shorter than in normal cats, and their structure appeared more compact and retracted. Slight changes were also observed in the anterior part of the ciliary epithelium. The anterior chamber angle region did not appear to be affected. Clear morphological correlations to the physiological blood flow data were observed in the anterior eye segment, pointing not only to functional but also morphological vascular abnormalities in this animal model for retinitis pigmentosa.

Architecture of dermatophyte cell Walls: Electron microscopic and biochemical analysis

NASA Technical Reports Server (NTRS)

Nozawa, Y.; Kitajima, Y.

1984-01-01

A review with 83 references on the cell wall structure of dermatophytes is presented. Topics discussed include separation and preparation of cell walls; microstructure of cell walls by electron microscopy; chemical composition of cell walls; structural model of cell walls; and morphological structure of cell walls.

A semi-automatic framework of measuring pulmonary arterial metrics at anatomic airway locations using CT imaging

NASA Astrophysics Data System (ADS)

Jin, Dakai; Guo, Junfeng; Dougherty, Timothy M.; Iyer, Krishna S.; Hoffman, Eric A.; Saha, Punam K.

2016-03-01

Pulmonary vascular dysfunction has been implicated in smoking-related susceptibility to emphysema. With the growing interest in characterizing arterial morphology for early evaluation of the vascular role in pulmonary diseases, there is an increasing need for the standardization of a framework for arterial morphological assessment at airway segmental levels. In this paper, we present an effective and robust semi-automatic framework to segment pulmonary arteries at different anatomic airway branches and measure their cross-sectional area (CSA). The method starts with user-specified endpoints of a target arterial segment through a custom-built graphical user interface. It then automatically detect the centerline joining the endpoints, determines the local structure orientation and computes the CSA along the centerline after filtering out the adjacent pulmonary structures, such as veins or airway walls. Several new techniques are presented, including collision-impact based cost function for centerline detection, radial sample-line based CSA computation, and outlier analysis of radial distance to subtract adjacent neighboring structures in the CSA measurement. The method was applied to repeat-scan pulmonary multirow detector CT (MDCT) images from ten healthy subjects (age: 21-48 Yrs, mean: 28.5 Yrs; 7 female) at functional residual capacity (FRC). The reproducibility of computed arterial CSA from four airway segmental regions in middle and lower lobes was analyzed. The overall repeat-scan intra-class correlation (ICC) of the computed CSA from all four airway regions in ten subjects was 96% with maximum ICC found at LB10 and RB4 regions.

Physiological, vascular and nanomechanical assessment of hybrid poplar leaf traits in micropropagated plants and plants propagated from root cuttings: A contribution to breeding programs.

PubMed

Ďurkovič, Jaroslav; Husárová, Hana; Javoříková, Lucia; Čaňová, Ingrid; Šuleková, Miriama; Kardošová, Monika; Lukáčik, Ivan; Mamoňová, Miroslava; Lagaňa, Rastislav

2017-09-01

Micropropagated plants experience significant stress from rapid water loss when they are transferred from an in vitro culture to either greenhouse or field conditions. This is caused both by inefficient stomatal control of transpiration and the change to a higher light intensity and lower humidity. Understanding the physiological, vascular and biomechanical processes that allow micropropagated plants to modify their phenotype in response to environmental conditions can help to improve both field performance and plant survival. To identify changes between the hybrid poplar [Populus tremula × (Populus × canescens)] plants propagated from in vitro tissue culture and those from root cuttings, we assessed leaf performance for any differences in leaf growth, photosynthetic and vascular traits, and also nanomechanical properties of the tracheary element cell walls. The micropropagated plants showed significantly higher values for leaf area, leaf length, leaf width and leaf dry mass. The greater leaf area and leaf size dimensions resulted from the higher transpiration rate recorded for this stock type. Also, the micropropagated plants reached higher values for chlorophyll a fluorescence parameters and for the nanomechanical dissipation energy of tracheary element cell walls which may indicate a higher damping capacity within the primary xylem tissue under abiotic stress conditions. The performance of the plants propagated from root cuttings was superior for instantaneous water-use efficiency which signifies a higher acclimation capacity to stressful conditions during a severe drought particularly for this stock type. Similarities were found among the majority of the examined leaf traits for both vegetative plant origins including leaf mass per area, stomatal conductance, net photosynthetic rate, hydraulic axial conductivity, indicators of leaf midrib vascular architecture, as well as for the majority of cell wall nanomechanical traits. This research revealed that there were no drawbacks in the leaf physiological performance which could be attributed to the micropropagated plants of fast growing hybrid poplar. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Transgene silencing of sucrose synthase in alfalfa (Medicago sativa L.) stem vascular tissue suggests a role for invertase in cell wall cellulose synthesis.

PubMed

Samac, Deborah A; Bucciarelli, Bruna; Miller, Susan S; Yang, S Samuel; O'Rourke, Jamie A; Shin, Sanghyun; Vance, Carroll P

2015-12-01

Alfalfa (Medicago sativa L.) is a widely adapted perennial forage crop that has high biomass production potential. Enhanced cellulose content in alfalfa stems would increase the value of the crop as a bioenergy feedstock. We examined if increased expression of sucrose synthase (SUS; EC 2.4.1.13) would increase cellulose in stem cell walls. Alfalfa plants were transformed with a truncated alfalfa phosphoenolpyruvate carboxylase gene promoter (PEPC7-P4) fused to an alfalfa nodule-enhanced SUS cDNA (MsSUS1) or the β-glucuronidase (GUS) gene. Strong GUS expression was detected in xylem and phloem indicating that the PEPC7-P4 promoter was active in stem vascular tissue. In contrast to expectations, MsSUS1 transcript accumulation was reduced 75-90 % in alfalfa plants containing the PEPC7-P4::MsSUS1 transgene compared to controls. Enzyme assays indicated that SUS activity in stems of selected down-regulated transformants was reduced by greater than 95 % compared to the controls. Although SUS activity was detected in xylem and phloem of control plants by in situ enzyme assays, plants with the PEPC7-P4::MsSUS1 transgene lacked detectable SUS activity in post-elongation stem (PES) internodes and had very low SUS activity in elongating stem (ES) internodes. Loss of SUS protein in PES internodes of down-regulated lines was confirmed by immunoblots. Down-regulation of SUS expression and activity in stem tissue resulted in no obvious phenotype or significant change in cell wall sugar composition. However, alkaline/neutral (A/N) invertase activity increased in SUS down-regulated lines and high levels of acid invertase activity were observed. In situ enzyme assays of stem tissue showed localization of neutral invertase in vascular tissues of ES and PES internodes. These results suggest that invertases play a primary role in providing glucose for cellulose biosynthesis or compensate for the loss of SUS1 activity in stem vascular tissue.

IMPACT OF CHRONIC ANTI-CHOLESTEROL THERAPY ON DEVELOPMENT OF MICROVASCULAR RAREFACTION IN THE METABOLIC SYNDROME

PubMed Central

Goodwill, Adam G.; Frisbee, Stephanie J.; Stapleton, Phoebe A.; James, Milinda E.; Frisbee, Jefferson C.

2011-01-01

Object The obese Zucker rat (OZR) model of the metabolic syndrome is partly characterized by moderate hypercholesterolemia in addition to other contributing co-morbidities. Previous results suggest that vascular dysfunction in OZR is associated with chronic reduction in vascular nitric oxide (NO) bioavailability and chronic inflammation, both frequently associated with hypercholesterolemia. As such, we evaluated the impact of chronic cholesterol reducing therapy on the development of impaired skeletal muscle arteriolar reactivity and microvessel density in OZR and its impact on chronic inflammation and NO bioavailability. Materials and Methods Beginning at 7 weeks of age, male OZR were treated with gemfibrozil, probucol, atorvastatin or simvastatin (in chow) for 10 weeks. Subsequently, plasma and vascular samples were collected for biochemical/molecular analyses, while arteriolar reactivity and microvessel network structure were assessed using established methodologies after 3, 6 and 10 weeks of drug therapy Results All interventions were equally effective at reducing total cholesterol, although only the statins also blunted the progressive reductions to vascular NO bioavailability, evidenced by greater maintenance of acetylcholine-induced dilator responses, an attenuation of adrenergic constrictor reactivity, and an improvement in agonist-induced NO production. Comparably, while minimal improvements to arteriolar wall mechanics were identified with any of the interventions, chronic statin treatment reduced the rate of microvessel rarefaction in OZR. Associated with these improvements was a striking statin-induced reduction in inflammation in OZR, such that numerous markers of inflammation were correlated with improved microvascular reactivity and density. However, using multivariate discriminant analyses, plasma RANTES, IL-10, MCP-1 and TNF-α were determined to be the strongest contributors to differences between groups, although their relative importance varied with time. Conclusions While the positive impact of chronic statin treatment on vascular outcomes in the metabolic syndrome are independent of changes to total cholesterol, and are more strongly associated with improvements to vascular NO bioavailability and attenuated inflammation, these results provide both a spatial and temporal framework for targeted investigation into mechanistic determinants of vasculopathy in the metabolic syndrome. PMID:19905967

NaCl - Changes stem morphology, anatomy and phloem structure in Lucerne (Medicago sativa cv. Gabès): Comparison of upper and lower internodes.

PubMed

Nja, Riheb Ben; Merceron, Bruno; Faucher, Mireille; Fleurat-Lessard, Pierrette; Béré, Emile

2018-02-01

In M. sativa cv. Gabès plants treated with 150mM NaCl, the height of the stem is decreased and the internode number, length and diameter are reduced. This depressive effect on growth, but also on photosynthetic activity and water balance, is accompanied by structural changes. In the upper internodes, NaCl treatment increases cambium development, so that the vascular ring is initiated earlier than in controls. In the lower internodes, the number of lignified phloem fibers is increased by NaCl, and their wall thickness is augmented, compared to controls; in the phloem complex, the nacreous layer is enlarged, the number of internal wall ingrowths is increased, but companion cells are damaged. In the treated lower internodes, few vessels occur in the secondary xylem, which is by contrast rich in lignified fibers and in wide vessels grouped in the metaxylem area; protoxylem parenchyma and adjacent pith are also lignified. In addition, in treated lower internodes, starch grains are less abundant than in controls, and this variation might be related to the decrease of photosynthesis. When taken together, qualitative and quantitative results indicate that the saline stress has a marked morpho-anatomical impact on the M. sativa Gabès stem. In particular, variations of secondary derivative distribution, increased wall thickening, lignification of phloem and xylem fibers and damage in the phloem complex are NaCl-induced responses, and are more expressed in the lower than in the upper internodes. The reinforcement of the stem lignified vasculature is thus a positive response to stress, but it has a negative impact on the quality of the forage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Downregulation of a UDP-Arabinomutase Gene in Switchgrass (Panicum virgatum L.) Results in Increased Cell Wall Lignin While Reducing Arabinose-Glycans

DOE PAGES

Willis, Jonathan D.; Smith, James A.; Mazarei, Mitra; ...

2016-10-26

Switchgrass (Panicum virgatum L.) is a C 4 perennial prairie grass and a dedicated feedstock for lignocellulosic biofuels. Saccharification and biofuel yields are inhibited by the plant cell wall's natural recalcitrance against enzymatic degradation. Plant hemicellulose polysaccharides such as arabinoxylans structurally support and cross-link other cell wall polymers. Grasses predominately have Type II cell walls that are abundant in arabinoxylan, which comprise nearly 25% of aboveground biomass. A primary component of arabinoxylan synthesis is uridine diphosphate (UDP) linked to arabinofuranose (Araf). A family of UDP-arabinopyranose mutase (UAM)/reversible glycosylated polypeptides catalyze the interconversion between UDP-arabinopyranose (UDP-Arap) and UDP-Araf. The expression ofmore » a switchgrass arabinoxylan biosynthesis pathway gene, PvUAM1, was decreased via RNAi to investigate its role in cell wall recalcitrance in the feedstock. PvUAM1 encodes a switchgrass homolog of UDP-arabinose mutase, which converts UDP-Arap to UDP-Araf. Southern blot analysis revealed each transgenic line contained between one to at least seven T-DNA insertions, resulting in some cases, a 95% reduction of native PvUAM1 transcript in stem internodes. Transgenic plants had increased pigmentation in vascular tissues at nodes, but were otherwise similar in morphology to the non-transgenic control. Cell wall-associated arabinose was decreased in leaves and stems by over 50%, but there was an increase in cellulose. In addition, there was a commensurate change in arabinose side chain extension. Cell wall lignin composition was altered with a concurrent increase in lignin content and transcript abundance of lignin biosynthetic genes in mature tillers. Enzymatic saccharification efficiency was unchanged in the transgenic plants relative to the control. Plants with attenuated PvUAM1 transcript had increased cellulose and lignin in cell walls. A decrease in cell wall-associated arabinose was expected, which was likely caused by fewer Araf residues in the arabinoxylan. The decrease in arabinoxylan may cause a compensation response to maintain cell wall integrity by increasing cellulose and lignin biosynthesis. In cases in which increased lignin is desired, e.g., feedstocks for carbon fiber production, downregulated UAM1 coupled with altered expression of other arabinoxylan biosynthesis genes might result in even higher production of lignin in biomass.« less

Downregulation of a UDP-Arabinomutase Gene in Switchgrass (Panicum virgatum L.) Results in Increased Cell Wall Lignin While Reducing Arabinose-Glycans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willis, Jonathan D.; Smith, James A.; Mazarei, Mitra

Switchgrass (Panicum virgatum L.) is a C 4 perennial prairie grass and a dedicated feedstock for lignocellulosic biofuels. Saccharification and biofuel yields are inhibited by the plant cell wall's natural recalcitrance against enzymatic degradation. Plant hemicellulose polysaccharides such as arabinoxylans structurally support and cross-link other cell wall polymers. Grasses predominately have Type II cell walls that are abundant in arabinoxylan, which comprise nearly 25% of aboveground biomass. A primary component of arabinoxylan synthesis is uridine diphosphate (UDP) linked to arabinofuranose (Araf). A family of UDP-arabinopyranose mutase (UAM)/reversible glycosylated polypeptides catalyze the interconversion between UDP-arabinopyranose (UDP-Arap) and UDP-Araf. The expression ofmore » a switchgrass arabinoxylan biosynthesis pathway gene, PvUAM1, was decreased via RNAi to investigate its role in cell wall recalcitrance in the feedstock. PvUAM1 encodes a switchgrass homolog of UDP-arabinose mutase, which converts UDP-Arap to UDP-Araf. Southern blot analysis revealed each transgenic line contained between one to at least seven T-DNA insertions, resulting in some cases, a 95% reduction of native PvUAM1 transcript in stem internodes. Transgenic plants had increased pigmentation in vascular tissues at nodes, but were otherwise similar in morphology to the non-transgenic control. Cell wall-associated arabinose was decreased in leaves and stems by over 50%, but there was an increase in cellulose. In addition, there was a commensurate change in arabinose side chain extension. Cell wall lignin composition was altered with a concurrent increase in lignin content and transcript abundance of lignin biosynthetic genes in mature tillers. Enzymatic saccharification efficiency was unchanged in the transgenic plants relative to the control. Plants with attenuated PvUAM1 transcript had increased cellulose and lignin in cell walls. A decrease in cell wall-associated arabinose was expected, which was likely caused by fewer Araf residues in the arabinoxylan. The decrease in arabinoxylan may cause a compensation response to maintain cell wall integrity by increasing cellulose and lignin biosynthesis. In cases in which increased lignin is desired, e.g., feedstocks for carbon fiber production, downregulated UAM1 coupled with altered expression of other arabinoxylan biosynthesis genes might result in even higher production of lignin in biomass.« less

Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease.

PubMed

Beck, Susanne C; Feng, Yuxi; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W

2017-01-01

Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease

PubMed Central

Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W.

2017-01-01

Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects. PMID:28575130

Structural variations among monocot emergent and amphibious species from lakes of the semi-arid region of Bahia, Brazil.

PubMed

Leite, K R B; França, F; Scatena, V I

2012-02-01

Temporary lakes are common in the semi-arid region of the State of Bahia and form water mirrors in the rainy season. In this period, various vegetal species appear having different life forms adapted to the seasonality conditions of the rainfall regime. This work surveyed the adaptive anatomical structures of some emergent and amphibious monocot species occurring in these lakes. We studied the anatomy of roots, rhizomes, leaves and scapes of Cyperus odoratus, Oxycaryum cubense, Pycreus macrostachyos (Cyperaceae) - amphibious species; and of Echinodorus grandiflorus (Alismataceae), Eichhornia paniculata (Pontederiaceae) and Habenaria repens (Orchidaceae) - emergent species. The anatomical features of the dermal, fundamental and vascular systems confirming the tendency of the adaptive convergence of these plants to temporary lacustrine the environment include: single layered epidermal cells with a thin cuticle layer in the aerial organs; the presence of air canals in all the organs; few or no supporting tissues; and less numerous conducting elements and thinner cell walls in the xylem. The reduction of the supporting tissues, the number of stomata, which can even be absent, and the number of conducting elements and the degree of cell wall lignification in the xylem of the emergent species is more accentuated than that of the amphibious species. The pattern of distribution of aerenchyma in the roots of the studied species was considered important to distinguish between amphibious and emergent life forms.

The respiratory system under weightlessness

NASA Technical Reports Server (NTRS)

Paiva, M.; Engel, L. A.; Hughes, J. M. B.; Guy, H. J.; Prisk, G. K.; West, J. B.

1987-01-01

Studies of pulmonary functions at rest to be studied on Spacelab mission D-2 are introduced. Gravity dependence of the distribution of ventilation (single breath washout, multibreath washout-washin); chest wall shape and motion; and the vascular compartment (lung blood flow, capillary volume, liquid content, diffusive capacity) are discussed.

Impaired Vascular Contractility and Aortic Wall Degeneration in Fibulin-4 Deficient Mice: Effect of Angiotensin II Type 1 (AT1) Receptor Blockade

PubMed Central

Moltzer, Els; te Riet, Luuk; Swagemakers, Sigrid M. A.; van Heijningen, Paula M.; Vermeij, Marcel; van Veghel, Richard; Bouhuizen, Angelique M.; van Esch, Joep H. M.; Lankhorst, Stephanie; Ramnath, Natasja W. M.; de Waard, Monique C.; Duncker, Dirk J.; van der Spek, Peter J.; Rouwet, Ellen V.; Danser, A. H. Jan; Essers, Jeroen

2011-01-01

Medial degeneration is a key feature of aneurysm disease and aortic dissection. In a murine aneurysm model we investigated the structural and functional characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and the potential therapeutic role of the angiotensin (Ang) II type 1 (AT1) receptor antagonist losartan in preventing aortic media degeneration. Adult mice with 2-fold (heterozygous Fibulin-4+/R) and 4-fold (homozygous Fibulin-4R/R) reduced expression of fibulin-4 displayed the histological features of cystic media degeneration as found in patients with aneurysm or dissection, including elastin fiber fragmentation, loss of smooth muscle cells, and deposition of ground substance in the extracellular matrix of the aortic media. The aortic contractile capacity, determined by isometric force measurements, was diminished, and was associated with dysregulation of contractile genes as shown by aortic transcriptome analysis. These structural and functional alterations were accompanied by upregulation of TGF-β signaling in aortas from fibulin-4 deficient mice, as identified by genome-scaled network analysis as well as by immunohistochemical staining for phosphorylated Smad2, an intracellular mediator of TGF-β. Tissue levels of Ang II, a regulator of TGF-β signaling, were increased. Prenatal treatment with the AT1 receptor antagonist losartan, which blunts TGF-β signaling, prevented elastic fiber fragmentation in the aortic media of newborn Fibulin-4R/R mice. Postnatal losartan treatment reduced haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4 animals, but did not affect aortic vessel wall structure. In conclusion, the AT1 receptor blocker losartan can prevent aortic media degeneration in a non-Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan does not affect aortic architecture, but does improve survival. These findings may extend the potential therapeutic application of inhibitors of the renin-angiotensin system to the preventive treatment of aneurysm disease. PMID:21858106

Correlations between axial stiffness and microstructure of a species of bamboo

PubMed Central

Mannan, Sayyad; Paul Knox, J.

2017-01-01

Bamboo is a ubiquitous monocotyledonous flowering plant and is a member of the true grass family Poaceae. In many parts of the world, it is widely used as a structural material especially in scaffolding and buildings. In spite of its wide use, there is no accepted methodology for standardizing a species of bamboo for a particular structural purpose. The task of developing structure–property correlations is complicated by the fact that bamboo is a hierarchical material whose structure at the nanoscopic level is not very well explored. However, we show that as far as stiffness is concerned, it is possible to obtain reliable estimates of important structural properties like the axial modulus from the knowledge of certain key elements of the microstructure. Stiffness of bamboo depends most sensitively on the size and arrangement of the fibre sheaths surrounding the vascular bundles and the arrangement of crystalline cellulose microfibrils in their secondary cell walls. For the species of bamboo studied in this work, we have quantitatively determined the radial gradation that the arrangement of fibres renders to the structure. The arrangement of the fibres gives bamboo a radially graded property variation across its cross section. PMID:28280545

Displacement of plasma protein and conduction velocity in rats under action of acceleration forces and hypokinesia

NASA Technical Reports Server (NTRS)

Baranski, S.; Edelwejn, Z.; Wojtkowiak, M.

1980-01-01

The permeability of capillary vessels was investigated in order to determine if acceleration alone or following prolonged hypokinesia would induce changes in the vascular wall leading to the penetration by l-albumins and/or proteins with larger molecules. In rats undergoing action of +5 Gz accelerations, no increase in vascular permeability, as tested with the use of (Cr-5k)-globulin, was demostrated. In rats immobilized for 4 weeks before centrifugation, rather weak migration of (Cr-51)-globulin from the vessels was observed. Immobilization resulted also in lowering of conduction velocity in the sciatic nerve.

Genetic modification of cerebral arterial wall: implications for prevention and treatment of cerebral vasospasm.

PubMed

Vijay, Anantha; Santhanam, R; Katusic, Zvonimir S

2006-10-01

Genetic modification of cerebral vessels represents a promising and novel approach for prevention and/or treatment of various cerebral vascular disorders, including cerebral vasospasm. In this review, we focus on the current understanding of the use of gene transfer to the cerebral arteries for prevention and/or treatment of cerebral vasospasm following subarachnoid hemorrhage (SAH). We also discuss the recent developments in vascular therapeutics, involving the autologous use of progenitor cells for repair of damaged vessels, as well as a cell-based gene delivery approach for the prevention and treatment of cerebral vasospasm.

Effects and mechanism of oridonin on pulmonary hypertension induced by chronic hypoxia-hypercapnia in rats.

PubMed

Wang, Liang-Xing; Sun, Yu; Chen, Chan; Huang, Xiao-Ying; Lin, Quan; Qian, Guo-Qing; Dong, Wei; Chen, Yan-Fan

2009-06-20

Pulmonary arterial hypertension (PAH) is characterized by suppressing apoptosis and enhancing cell proliferation in the vascular wall. Inducing pulmonary artery smooth muscle cells (PASMC) apoptosis had been regarded as a therapeutic approach for PAH. Oridonin can cause apoptosis in many cell lines, while little has been done to evaluate its effect on PASMC. Thirty male Sprague-Dawley rats were randomly assigned to three groups: normal control (NC); hypoxia-hypercapnia (HH); Hypoxia-hypercapnia + oridonin (HHO). Rats were exposed to hypoxia-hypercapnia for four weeks. Cultured human PASMC (HPASMC) were assigned to three groups: normoxia (NO); hypoxia (HY); hypoxia + oridonin (HO). The mean pulmonary artery pressure, mass ratio of right ventricle over left ventricle plus septum (RV/(LV + S)), the ratio of thickness of the pulmonary arteriole wall to vascular external diameter (WT%) and the ratio of the vessel wall area to the total area (WA%) were measured. Morphologic changes of pulmonary arteries were observed under light and electron microscopes. The apoptotic characteristics in vitro and in vivo were detected. The mPAP, RV/(LV + S), WT%, and WA% in the HH group were significantly greater than those in the NC (P < 0.01) and HHO groups (P < 0.01); the activities of caspase-3 and caspase-9, and the expressions of Bax, cyt-C and apoptotic index (AI) in the group HH were less than those in the NC and HHO groups; and the expression of Bcl-2 in group HH was greater than that in the NC and HHO groups. HPASMC mitochondrial membrane potentials in group HO was lower than in group HY (P < 0.01), and cyt-C in the cytoplasm, AI, and caspase-9 in the HO group were greater than that in the HY group (P < 0.01), but the expression of Bcl-2 in the HO group was less than that in the HY group (P < 0.05). The results suggest that oridonin can lower pulmonary artery pressure effectively, and inhibit pulmonary artery structural remodeling by inducing smooth cell apoptosis via a mitochondria-dependent pathway.

Hemodynamics of physiological blood flow in the aorta with nonlinear anisotropic heart valve

NASA Astrophysics Data System (ADS)

Sotiropoulos, Fotis; Gilmanov, Anvar; Stolarski, Henryk

2016-11-01

The hemodynamic blood flow in cardiovascular system is one of the most important factor, which causing several vascular diseases. We developed a new Curvilinear Immersed Boundary - Finite Element - Fluid Structure Interaction (CURVIB-FE-FSI) method to analyze hemodynamic of pulsatile blood flow in a real aorta with nonlinear anisotropic aortic valve at physiological conditions. Hyperelastic material model, which is more realistic for describing heart valve have been incorporated in the CURVIB-FE-FSI code to simulate interaction of aortic heart valve with pulsatile blood flow. Comparative studies of hemodynamics for linear and nonlinear models of heart valve show drastic differences in blood flow patterns and hence differences of stresses causing impact at leaflets and aortic wall. This work is supported by the Lillehei Heart Institute at the University of Minnesota.

Chronic laminitis: strategic hoof wall resection.

PubMed

Rucker, Amy

2010-04-01

In the chronic-laminitic foot, severe soft-tissue compression and compromised circulation can result in osteitis and sepsis at the margin of the distal phalanx. Resultant inflammation and sepsis may cause the coronary corium to swell, drain, or separate from the hoof capsule, usually within 8 weeks of laminitis onset. Slow-onset cases of soft-tissue impingement can develop secondary to distal phalanx displacement due to lack of wall attachment. With either presentation, partial upper wall resection is required to reverse compression and vascular impingement by the hoof capsule. If the pathology is not overwhelming, the area reepithelializes and grows attached tubular horn. Firm bandaging and restricted exercise until tubular horn has regrown enhances recovery and the return of a strong hoof. Copyright 2010 Elsevier Inc. All rights reserved.

Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ribeiro Júnior, Rogério Faustino, E-mail: rogeriofaustinoribeiro@hotmail.com; Marques, Vinicius Bermond; Nunes, Dieli Oliveira

Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposuremore » increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration–response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT{sub 1} receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O{sub 2}{sup −} production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. - Highlights: • Tributyltin chloride reduces estrogen levels in female rats. • Treatment with TBT resulted in increased contractile response to phenylephrine. • Collagen deposition could be responsible for vascular stiffness after TBT exposure.« less

Abdominal wall reconstruction using a combination of free tensor fasciae lata and anterolateral thigh myocutaneous flap: a prospective study in 16 patients.

PubMed

Lv, Yang; Cao, Dongsheng; Guo, Fangfang; Qian, Yunliang; Wang, Chen; Wang, Danru

2015-08-01

Reconstruction of the abdominal wall continues to be a challenging problem for plastic surgeons. Transposition of well-vascularized flap tissue is the most effective way to repair composite abdominal wall defects. We retrospectively reviewed the treatment of such patients and assessed the reconstructive technique using combination of an inlay of bioprosthetic materials and a united thigh flap. A retrospective review of patients' records in the department was carried out. In total, 16 patients who underwent immediate abdominal wall reconstruction between 2000 and 2013 were identified. Patients' health status, defect sizes, and surgical technique were obtained from medical charts. The immediate reconstruction surgery of the abdominal wall was successful in all patients. One patient with dermatofibrosarcoma protuberans experienced recurrences at the former site. One patient died because of liver metastases at 21 months after surgery. No incisional hernia or infection in this series of patients was observed. Full-thickness, giant defects of the complicated abdominal wall can be repaired successfully with relatively minor complications using this reconstructive technique. Copyright © 2015 Elsevier Inc. All rights reserved.

H2S dependent and independent anti-inflammatory activity of zofenoprilat in cells of the vascular wall.

PubMed

Monti, Martina; Terzuoli, Erika; Ziche, Marina; Morbidelli, Lucia

2016-11-01

Cardiovascular diseases as atherosclerosis are associated to an inflammatory state of the vessel wall which is accompanied by endothelial dysfunction, and adherence and activation of circulating inflammatory cells. Hydrogen sulfide, a novel cardiovascular protective gaseous mediator, has been reported to exert anti-inflammatory activity. We have recently demonstrated that the SH containing ACE inhibitor zofenoprilat, the active metabolite of zofenopril, controls the angiogenic features of vascular endothelium through H 2 S enzymatic production by cystathionine gamma lyase (CSE). Based on H 2 S donor/generator property of zofenoprilat, the objective of this study was to evaluate whether zofenoprilat exerts anti-inflammatory activity in vascular cells through its ability to increase H 2 S availability. Here we found that zofenoprilat, in a CSE/H 2 S-mediated manner, abolished all the inflammatory features induced by interlukin-1beta (IL-1β) in human umbilical vein endothelial cells (HUVEC), especially the NF-κB/cyclooxygenase-2 (COX-2)/prostanoid biochemical pathway. The pre-incubation with zofenoprilat/CSE dependent H 2 S prevented IL-1β induced paracellular hyperpermeability through the control of expression and localization of cell-cell junctional markers ZO-1 and VE-cadherin. Moreover, zofenoprilat/CSE dependent H 2 S reduced the expression of the endothelial markers CD40 and CD31, involved in the recruitment of circulating mononuclear cells and platelets. Interestingly, this anti-inflammatory activity was also confirmed in vascular smooth muscle cells and fibroblasts as zofenoprilat reduced, in both cell lines, proliferation, migration and COX-2 expression induced by IL-1β, but independently from the SH moiety and H 2 S availability. These in vitro data document the anti-inflammatory activity of zofenoprilat on vascular cells, reinforcing the cardiovascular protective effect of this multitasking drug. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interstitial Fluid Flow and Drug Delivery in Vascularized Tumors: A Computational Model

PubMed Central

Welter, Michael; Rieger, Heiko

2013-01-01

Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider–with the help of a theoretical model–the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various strategies to increase drug exposure time of tumor cells. PMID:23940570

Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

PubMed

Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; de Araújo, Julia F P; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B; Stefanon, Ivanita

2016-03-15

Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Step down Vascular Calcification Analysis using State-of-the-Art Nanoanalysis Techniques

PubMed Central

Curtze, Sven C.; Kratz, Marita; Steinert, Marian; Vogt, Sebastian

2016-01-01

New insights into the architecture and formation mechanisms of calcific lesions down to the nanoscale open a better understanding of atherosclerosis and its pathogenesis. Scanning electron – and atomic force microscope based nano-analytical characterization techniques were adapted to the assessment of an ex-vivo calcified coronary artery. Human atherosclerotic tissue and bone tissue reside a typical chemistry of Magnesium and Sodium rich Calcium phosphates, identified as whitlockite and Calcium apatite, respectively. Despite the obvious similarities in both chemistry and crystallography, there are also clear differences between calcified vascular tissue and bone such as the highly oriented growth in bone, revealing meso-crystal character, as opposed to the anisotropic character of calcified vascular lesions. While the grain size in vascular calcified plaques is in the range of nanometers, the grain size in bone appears larger. Spherical calcific particles present in both the coronary artery wall and embedded in plaques reveal concentric layers with variations in both organic content and degree of hydration. PMID:26980376

Step down Vascular Calcification Analysis using State-of-the-Art Nanoanalysis Techniques.

PubMed

Curtze, Sven C; Kratz, Marita; Steinert, Marian; Vogt, Sebastian

2016-03-16

New insights into the architecture and formation mechanisms of calcific lesions down to the nanoscale open a better understanding of atherosclerosis and its pathogenesis. Scanning electron - and atomic force microscope based nano-analytical characterization techniques were adapted to the assessment of an ex-vivo calcified coronary artery. Human atherosclerotic tissue and bone tissue reside a typical chemistry of Magnesium and Sodium rich Calcium phosphates, identified as whitlockite and Calcium apatite, respectively. Despite the obvious similarities in both chemistry and crystallography, there are also clear differences between calcified vascular tissue and bone such as the highly oriented growth in bone, revealing meso-crystal character, as opposed to the anisotropic character of calcified vascular lesions. While the grain size in vascular calcified plaques is in the range of nanometers, the grain size in bone appears larger. Spherical calcific particles present in both the coronary artery wall and embedded in plaques reveal concentric layers with variations in both organic content and degree of hydration.

The Nature of Dynamic Arteriolar Vasoreactivity: A Mini-Review and A classification Scheme

DTIC Science & Technology

1993-06-08

small veins. In this videomicroscopy study we always examined a junction of a true transverse (TR) and a true terminal (TE) arteriole within the muscle...by LDF), comparisons of vascular wall behavior were made from intravital videomicroscopy records. Vasoreactive behavior of the microvessels was

The effects of nicotine administration on the pathophysiology of rat aortic wall.

PubMed

Kugo, H; Zaima, N; Tanaka, H; Urano, T; Unno, N; Moriyama, T

2017-01-01

Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats.

Multi-ligand nanoparticles for targeted drug delivery to the injured vascular wall

NASA Astrophysics Data System (ADS)

Kona, Soujanya

Pathological conditions like coronary artery disease, acute myocardial infarction, stroke, and peripheral artery diseases as well as cardiovascular interventions used in the treatment of coronary artery diseases such as angioplasty and stenting damage/injure the blood vessel wall, leading to inflamed or activated endothelial cells that have been implicated in events leading to thrombosis, inflammation, and restenosis. Oral administration of anti-coagulant and anti-inflammatory drugs causes systemic toxicity, bleeding, patient incompliance, and inadequate amounts of drugs at the injured area. Though drug-eluting stents have shown therapeutic benefits, complications such as in-stent restenosis and late thrombosis still remain and are a cause for concern. Rapid growth in the field of nanotechnology and nanoscience in recent years has paved the way for new targeted and controlled drug delivery strategies. In this perspective, the development of biodegradable nanoparticles for targeted intracellular drug delivery to the inflamed endothelial cells may offer an improved avenue for treatment of cardiovascular diseases. The major objective of this research was to develop "novel multi-ligand nanoparticles," as drug carriers that can efficiently target and deliver therapeutic agents to the injured/inflamed vascular cells under dynamic flow conditions. Our approach mimics the natural binding ability of platelets to injured/activated endothelial cells through glycoprotein Ib (GPIb) bound to P-selectin expressed on inflamed endothelial cells and to the subendothelium through GPIb binding to von Willebrand factor (vWF) deposited onto the injured vascular wall. Our design also exploits the natural cell membrane translocation ability of the internalizing cell peptide - trans-activating transcriptor (TAT) to enhance the nanoparticle uptake by the targeted cells. Our hypothesis is that these multi-ligand nanoparticles would show an increased accumulation at the injury site since GPIb specially binds to both P-selectin expressed on damaged endothelial cells and vWF deposited on injured subendothelium while the cell penetrating peptide -- TAT would facilitate enhanced uptake of these nanoparticles by the damaged vascular cells. To test this hypothesis, fluorescent drug loaded poly (D, L-lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) nanoparticles (PLGA-PEG NPs) were formulated using a standard double emulsion method. We further conjugated GPIb and TAT via carbodiimide and avidin-biotin chemistry to the PLGA-PEG nanoparticles. Characterization of these nanoparticles indicated the average size to be about 200nm. Endothelial cell uptake studies indicated an optimal nanoparticle incubation time of one hour and optimal dose of 400 mug/ml. Biocompatibility results showed these particles to be non-toxic to endothelial cells. Moreover, dexamethasone release profiles from the nanoparticles demonstrated their ability to provide a sustained drug release over four weeks. Static and dynamic uptake studies of control, GPIb-conjugated, and GPIb-TAT-conjugated PLGA-PEG nanoparticles on activated endothelial cells exhibited an increased adhesion and uptake of GPIb-TAT conjugated PLGA-PEG nanoparticles compared to control nanoparticles. A similar trend of significantly higher adhesion of GPIb-TAT conjugated PLGA-PEG nanoparticles to the injured vessel wall was also observed in preliminary ex-vivo studies using the rat carotid injury model. These results suggest that "our novel multi-ligand NPs" would provide a unique active targeting strategy. This system would rapidly target and deliver therapeutic agents to the injured vascular wall under flow conditions. It could also serve as an effective therapeutic delivery system to treat the complications associated with cardiovascular diseases.

Pulmonary blood flow and pulmonary hypertension: Is the pulmonary circulation flowophobic or flowophilic?

PubMed Central

Kulik, Thomas J.

2012-01-01

Increased pulmonary blood flow (PBF) is widely thought to provoke pulmonary vascular obstructive disease (PVO), but the impact of wall shear stress in the lung is actually poorly defined. We examined information from patients having cardiac lesions which impact the pulmonary circulation in distinct ways, as well as experimental studies, asking how altered hemodynamics impact the risk of developing PVO. Our results are as follows: (1) with atrial septal defect (ASD; increased PBF but low PAP), shear stress may be increased but there is little tendency to develop PVO; (2) with normal PBF but increased pulmonary vascular resistance (PVR; mitral valve disease) shear stress may also be increased but risk of PVO still low; (3) with high PVR and PBF (e.g., large ventricular septal defect), wall shear stress is markedly increased and the likelihood of developing PVO is much higher than with high PBF or PAP only; and (4) with ASD, experimental and clinical observations suggest that increased PBF plus another stimulus (e.g., endothelial inflammation) may be required for PVO. We conclude that modestly increased wall shear stress (e.g., ASD) infrequently provokes PVO, and likely requires other factors to be harmful. Likewise, increased PAP seldom causes PVO. Markedly increased wall shear stress may greatly increase the likelihood of PVO, but we cannot discriminate its effect from the combined effects of increased PAP and PBF. Finally, the age of onset of increased PAP may critically impact the risk of PVO. Some implications of these observations for future investigations are discussed. PMID:23130101

Avoiding Complications in Abdominal Wall Surgery: A Mathematical Model to Predict the Course of the Motor Innervation of the Rectus Abdominis.

PubMed

Tessone, Ariel; Nava, Maurizio; Blondeel, Phillip; Spano, Andrea

2016-02-01

Ever since its introduction, the transverse rectus abdominis myocutaneous flap has become the mainstay of autologous breast reconstruction. However, concerns regarding donor site morbidity due to the breach of abdominal wall musculature integrity soon followed. Muscle-sparing techniques, eventually eliminating the muscle from the flap all-together with the deep inferior epigastric artery perforator flap, did not eliminate the problem of abdominal wall weakness. This led to the conclusion that motor innervation might be at fault. Studies have shown that even in the presence of an intact rectus abdominis muscle, and an intact anterior rectus sheath, denervation of the rectus abdominis muscle results in significant abdominal wall weakness leading to superior and inferior abdominal bulges, and abdominal herniation. Our aim was to establish a mathematical model to predict the location of the motor innervation to the rectus abdominis muscle, and thus provide surgeons with a tool that will allow them to reduce abdominal morbidity during deep inferior epigastric artery perforator and free muscle-sparing transverse rectus abdominis myocutaneous surgery. We dissected 42 cadaveric hemiabdomens and mapped the course of the thoracolumbar nerves. We then standardized and analyzed our findings and presented them as a relative map which can be adjusted to body type and dimensions. Our dissections show that the motor innervation is closely related to the lateral vascular supply. Thus, when possible, we support the preferred utilization of the medial vascular supply, and the preservation of the lateral supply and motor innervation.

Dirigent proteins and dirigent sites in lignifying tissues

NASA Technical Reports Server (NTRS)

Burlat, V.; Kwon, M.; Davin, L. B.; Lewis, N. G.

2001-01-01

Tissue-specific dirigent protein gene expression and associated dirigent (site) localization were examined in various organs of Forsythia intermedia using tissue printing, in situ mRNA hybridization and immunolabeling techniques, respectively. Dirigent protein gene expression was primarily noted in the undifferentiated cambial regions of stem sections, whereas dirigent protein sites were detected mainly in the vascular cambium and ray parenchyma cell initials. Immunolocalization also revealed cross-reactivity with particular regions of the lignified cell walls, these being coincident with the known sites of initiation of lignin deposition. These latter regions are considered to harbor contiguous arrays of dirigent (monomer binding) sites for initiation of lignin biopolymer assembly. Dirigent protein mRNA expression was also localized in the vascular regions of roots and petioles, whereas in leaves the dirigent sites were primarily associated with the palisade layers and the vascular bundle. That is, dirigent protein mediated lignan biosynthesis was initiated primarily in the cambium and ray cell initial regions of stems as well as in the leaf palisade layers, this being in accordance with the occurrence of the lignans for defense purposes. Within lignified secondary xylem cell walls, however, dirigent sites were primarily localized in the S(1) sublayer and compound middle lamella, these being coincident with previously established sites for initiation of macromolecular lignin biosynthesis. Once initiation occurs, lignification is proposed to continue through template polymerization.

Vascular wall function in insulin-resistant JCR:LA-cp rats: role of male and female sex.

PubMed

O'Brien, S F; Russell, J C; Dolphin, P J; Davidge, S T

2000-08-01

Vascular wall function was assessed in obese insulin-resistant (cp/cp) and lean normal (+/?), male and female, JCR:LA-cp rats. Both male and female cp/cp rats showed enhanced maximum contractility in response to norepinephrine; impaired smooth muscle in response to sodium nitroprusside, a nitric oxide (NO) donor; and impaired relaxation in response to acetylcholine (ACh), compared with their lean counterparts. The abnormalities were similar in male and female cp/cp rats. The NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), inhibited ACh-mediated relaxation significantly in male rats, both cp/cp and +/?. The inhibition of ACh-mediated relaxation by L-NAME in +/? females was less, with no reduction in maximal relaxation, and was absent in cp/cp females. These effects suggest that the relative importance of NO in the endothelial modulation of smooth muscle contractility is greater in male rats. The results are consistent with a decreased role for endothelial NO in the cp/cp rats of both sexes and a reduction in NO-independent cholinergic relaxation in the male cp/cp rat. This NO-independent mechanism is not affected in the female cp/cp rats. The relatively small differences between males and females in smooth muscle cell and vascular function may contribute to sex-related differences in the atherogenesis, vasospasm, and ischemic damage associated with the obese insulin-resistant state.

Descending aortic injury by a thoracic pedicle screw during posterior reconstructive surgery: a case report.

PubMed

Watanabe, Kei; Yamazaki, Akiyoshi; Hirano, Toru; Izumi, Tomohiro; Sano, Atsuki; Morita, Osamu; Kikuchi, Ren; Ito, Takui

2010-09-15

Case report. To describe an iatrogenic aortic injury by pedicle screw instrumentation during posterior reconstructive surgery of spinal deformity. Iatrogenic major vascular injuries during anterior instrumentation procedures have been reported by several authors, but there have been few reports regarding iatrogenic major vascular injuries during posterior instrumentation procedures. A 57-year-old woman with thoracolumbar kyphosis due to osteoporotic T12 vertebral fracture underwent posterior correction and fusion (T10-L2), using segmental pedicle screw construct concomitant with T12 pedicle subtraction osteotomy. Postoperative routine plain radiographs and computed tomography myelography demonstrated a misplaced left T10 pedicle screw, which was in contact with the posteromedial aspect of the thoracic aorta, and suspected penetration of the aortic wall. The patient underwent removal of the pedicle screw, and repair of the penetrated aortic wall through a simultaneous anterior-posterior approach. The patient tolerated the procedure well without neurologic sequelae, and was discharged several days after removal of a left tube thoracostomy. Plain radiographs demonstrated solid fusion at the osteotomy site and no loosening of hardware. Preoperative neurologic symptoms improved completely at 18-months follow-up. Use of pedicle screw instrumentation has the potential to cause major vascular injury during posterior spinal surgery, and measures to prevent this complication must be taken. Timely diagnosis and treatment are essential to prevent both early and delayed complications and death.

Modeling of flow-induced shear stress applied on 3D cellular scaffolds: Implications for vascular tissue engineering.

PubMed

Lesman, Ayelet; Blinder, Yaron; Levenberg, Shulamit

2010-02-15

Novel tissue-culture bioreactors employ flow-induced shear stress as a means of mechanical stimulation of cells. We developed a computational fluid dynamics model of the complex three-dimensional (3D) microstructure of a porous scaffold incubated in a direct perfusion bioreactor. Our model was designed to predict high shear-stress values within the physiological range of those naturally sensed by vascular cells (1-10 dyne/cm(2)), and will thereby provide suitable conditions for vascular tissue-engineering experiments. The model also accounts for cellular growth, which was designed as an added cell layer grown on all scaffold walls. Five model variants were designed, with geometric differences corresponding to cell-layer thicknesses of 0, 50, 75, 100, and 125 microm. Four inlet velocities (0.5, 1, 1.5, and 2 cm/s) were applied to each model. Wall shear-stress distribution and overall pressure drop calculations were then used to characterize the relation between flow rate, shear stress, cell-layer thickness, and pressure drop. The simulations showed that cellular growth within 3D scaffolds exposes cells to elevated shear stress, with considerably increasing average values in correlation to cell growth and inflow velocity. Our results provide in-depth analysis of the microdynamic environment of cells cultured within 3D environments, and thus provide advanced control over tissue development in vitro. 2009 Wiley Periodicals, Inc.

miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular aging.

PubMed

Zhan, Jiaxin; Qin, Shanshan; Lu, Lili; Hu, Xiamin; Zhou, Jun; Sun, Yeying; Yang, Jian; Liu, Ying; Wang, Zunzhe; Tan, Ning; Chen, Jiyan; Zhang, Chunxiang

2016-11-26

Both HIV and antiretroviral therapy could induce vascular aging with unclear mechanisms. In this study, via microarray analysis, we identified, for the first time, that miR-34a expression was significantly increased in both HIV-infected, and antiretroviral agents-treated vessels and vascular endothelial cells (ECs) from these vessels. In cultured ECs, miR-34a expression was significantly increased by HIV-Tat protein and by the antiretroviral agents, lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce EC senescence, which was inhibited by miR-34a inhibition. In contrast, EC senescence was exacerbated by miR-34a overexpression. In addition, the vascular ECs isolated from miR-34a knockout mice were resistant to HIV and antiretroviral agents-mediated senescence. In vivo, miR-34a expression in mouse vascular walls and their ECs was increased by antiretroviral therapy and by HIV-1 Tat transgenic approach. miR-34a inhibition could effectively inhibit both HIV-Tat protein and antiretroviral therapy-induced vascular aging in mice. The increased miR-34a was induced via p53, whereas Sirt1 was a downstream target gene of miR-34a in both HIV-Tat protein and antiretroviral agents-treated ECs and vessels. The study has demonstrated that miR-34a is a common link in both HIV and antiretroviral therapy-mediated vascular aging.

Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy

PubMed Central

Park, Yang-Gyu; Choi, Jawun; Jung, Hye-Kang; Song, In Kyu; Shin, Yongwhan; Park, Sang-Youel; Seol, Jae-Won

2017-01-01

Early pregnancy is characterized by an increase in the blood volume of the uterus for embryonic development, thereby exerting fluid shear stress (FSS) on the vascular walls. The uterus experiences vascular remodeling to accommodate the increased blood flow. The blood flow-induced FSS elevates the expression of vascular endothelial growth factors (VEGFs) and their receptors, and regulates vascular remodeling through the activation of VEGF receptor-3 (VEGFR-3). However, the mechanisms responsible for FSS-induced VEGFR-3 expression in the uterus during pregnancy are unclear. In this study, we demonstrate that vascular remodeling in the uterus during pregnancy is regulated by FSS-induced VEGFR-3 expression. We examined the association between VEGFR-3 and FSS through in vivo and in vitro experiments. In vivo experiments revealed VEGFR-3 expression in the CD31-positive region of the uterus of pregnant mice; VEGF-C (ligand for VEGFR-3) was undetected in the uterus. These results confirmed that VEGFR-3 expression in the endometrium is independent of its ligand. In vitro studies experiments revealed that FSS induced morphological changes and increased VEGFR-3 expression in human uterine microvascular endothelial cells. Thus, VEGFR-3 activation by FSS is associated with vascular remodeling to allow increased blood flow in the uterus during pregnancy. PMID:28849193

Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy.

PubMed

Park, Yang-Gyu; Choi, Jawun; Jung, Hye-Kang; Song, In Kyu; Shin, Yongwhan; Park, Sang-Youel; Seol, Jae-Won

2017-10-01

Early pregnancy is characterized by an increase in the blood volume of the uterus for embryonic development, thereby exerting fluid shear stress (FSS) on the vascular walls. The uterus experiences vascular remodeling to accommodate the increased blood flow. The blood flow‑induced FSS elevates the expression of vascular endothelial growth factors (VEGFs) and their receptors, and regulates vascular remodeling through the activation of VEGF receptor-3 (VEGFR-3). However, the mechanisms responsible for FSS-induced VEGFR-3 expression in the uterus during pregnancy are unclear. In this study, we demonstrate that vascular remodeling in the uterus during pregnancy is regulated by FSS-induced VEGFR-3 expression. We examined the association between VEGFR-3 and FSS through in vivo and in vitro experiments. In vivo experiments revealed VEGFR-3 expression in the CD31-positive region of the uterus of pregnant mice; VEGF-C (ligand for VEGFR‑3) was undetected in the uterus. These results confirmed that VEGFR-3 expression in the endometrium is independent of its ligand. In vitro studies experiments revealed that FSS induced morphological changes and increased VEGFR-3 expression in human uterine microvascular endothelial cells. Thus, VEGFR-3 activation by FSS is associated with vascular remodeling to allow increased blood flow in the uterus during pregnancy.

3D MR flow analysis in realistic rapid-prototyping model systems of the thoracic aorta: comparison with in vivo data and computational fluid dynamics in identical vessel geometries.

PubMed

Canstein, C; Cachot, P; Faust, A; Stalder, A F; Bock, J; Frydrychowicz, A; Küffer, J; Hennig, J; Markl, M

2008-03-01

The knowledge of local vascular anatomy and function in the human body is of high interest for the diagnosis and treatment of cardiovascular disease. A comprehensive analysis of the hemodynamics in the thoracic aorta is presented based on the integration of flow-sensitive 4D MRI with state-of-the-art rapid prototyping technology and computational fluid dynamics (CFD). Rapid prototyping was used to transform aortic geometries as measured by contrast-enhanced MR angiography into realistic vascular models with large anatomical coverage. Integration into a flow circuit with patient-specific pulsatile in-flow conditions and application of flow-sensitive 4D MRI permitted detailed analysis of local and global 3D flow dynamics in a realistic vascular geometry. Visualization of characteristic 3D flow patterns and quantitative comparisons of the in vitro experiments with in vivo data and CFD simulations in identical vascular geometries were performed to evaluate the accuracy of vascular model systems. The results indicate the potential of such patient-specific model systems for detailed experimental simulation of realistic vascular hemodynamics. Further studies are warranted to examine the influence of refined boundary conditions of the human circulatory system such as fluid-wall interaction and their effect on normal and pathological blood flow characteristics associated with vascular geometry. (c) 2008 Wiley-Liss, Inc.

Evaluation of alginate dialdehyde cross-linked gelatin hydrogel as a biodegradable sealant for polyester vascular graft.

PubMed

Manju, Saraswathy; Muraleedharan, Chirathodi Vayalappil; Rajeev, Adathala; Jayakrishnan, Attipettah; Joseph, Roy

2011-07-01

Vascular grafts are devices intended to replace compromised arteries in the body and grafts made of polyethylene terephthalate (PET) fabric have been used mainly for synthetic grafting procedures involving medium to large diameter vascular grafts. Though porosity of the graft permits tissue in-growth, it would lead to bleeding through the graft walls immediately after implantation. So it is essential to seal the pores either by preclotting with patient's own blood or by other sealing materials prior to implantation in order to prevent blood leakage through the graft wall. Biodegradable hydrogel materials are ideal candidates for this purpose. Apart from sealing the pores, they offer biocompatible and low-thrombogenic surfaces when coated on vascular graft. In the present study, a biodegradable hydrogel, derived from oxidized alginate and gelatin, has been deposited on PET grafts by dip coating and were characterized for its efficacy on sealing the pores of the graft. Water permeability in the static and pulsatile conditions, burst strength, in vitro cell culture cytotoxicity, hemocompatibility, and endothelial cell adhesion and proliferation of the coated grafts were investigated. Results showed that the alginate dialdehyde cross-linked gelatin hydrogel was nontoxic, hemocompatible, and was efficient in sealing the pores of the graft. Blood perfusion study showed that when hydrogel-coated grafts were exposed to blood for 30 min, they showed little affinity toward platelets or leukocytes. Hemolytic potential of PET was significantly reduced when it was coated with hydrogel. Improved adhesion and proliferation of endothelial cells were observed when PET grafts were coated with hydrogel. Results also showed that coating with hydrogel did not affect the burst strength of the PET graft. Copyright © 2011 Wiley Periodicals, Inc.

Scaffold-free, Human Mesenchymal Stem Cell-Based Tissue Engineered Blood Vessels.

PubMed

Jung, Youngmee; Ji, HaYeun; Chen, Zaozao; Fai Chan, Hon; Atchison, Leigh; Klitzman, Bruce; Truskey, George; Leong, Kam W

2015-10-12

Tissue-engineered blood vessels (TEBV) can serve as vascular grafts and may also play an important role in the development of organs-on-a-chip. Most TEBV construction involves scaffolding with biomaterials such as collagen gel or electrospun fibrous mesh. Hypothesizing that a scaffold-free TEBV may be advantageous, we constructed a tubular structure (1 mm i.d.) from aligned human mesenchymal cell sheets (hMSC) as the wall and human endothelial progenitor cell (hEPC) coating as the lumen. The burst pressure of the scaffold-free TEBV was above 200 mmHg after three weeks of sequential culture in a rotating wall bioreactor and perfusion at 6.8 dynes/cm(2). The interwoven organization of the cell layers and extensive extracellular matrix (ECM) formation of the hMSC-based TEBV resembled that of native blood vessels. The TEBV exhibited flow-mediated vasodilation, vasoconstriction after exposure to 1 μM phenylephrine and released nitric oxide in a manner similar to that of porcine femoral vein. HL-60 cells attached to the TEBV lumen after TNF-α activation to suggest a functional endothelium. This study demonstrates the potential of a hEPC endothelialized hMSC-based TEBV for drug screening.

Immunocytochemical analysis of the subcellular distribution of ferritin in Imperata cylindrica (L.) Raeuschel, an iron hyperaccumulator plant.

PubMed

de la Fuente, Vicenta; Rodríguez, Nuria; Amils, Ricardo

2012-05-01

Ferritin is of interest at the structural and functional level not only as storage for iron, a critical element, but also as a means to prevent cell damage produced by oxidative stress. The main objective of this work was to confirm by immunocytochemistry the presence and the subcellular distribution of the ferritin detected by Mösbauer spectroscopy in Imperata cylindrica, a plant which accumulates large amounts of iron. The localization of ferritin was performed in epidermal, parenchymal and vascular tissues of shoots and leaves of I. cylindrica. The highest density of immunolabeling in shoots appeared in the intracellular space of cell tissues, near the cell walls and in the cytoplasm. In leaves, ferritin was detected in the proximity of the dense network of the middle lamella of cell walls, following a similar path to that observed in shoots. Immunolabeling was also localized in chloroplasts. The abundance of immunogold labelling in mitochondria for I. cylindrica was rather low, probably because the study dealt with tissues from old plants. These results further expand the localization of ferritin in cell components other than chloroplasts and mitochondria in plants. Copyright © 2011 Elsevier GmbH. All rights reserved.

[PHACES syndrome].

PubMed

Morcillo Azcárate, J; Bernabeu-Wittel, J; Fernández-Pineda, I; Conejo-Mir, M D; Tuduri Limousin, I; Aspiazu Salinas, D A; de Agustín Asensio, J C

2010-04-01

PHACES syndrome associates a segmental facial hemangioma with cerebral malformations, aortic branches/cranial arteries anomalies, cardiac defects, eye anomalies or ventral wall defects. The aim of this study is to analyze our experience with this syndrome. Retrospective study of the cases seen at our unit in the last year. We treat 4 cases; 3 girls and 1 child. Besides the segmental hemangioma they presented: 3 vascular cerebral malformations; 2 structural cardiopathies; 2 cerebral malformations, 1 microftalmia. We did not find ventral wall defects. A case received treatment with two cycles of metilprednisolone i.v. and oral prednisone, with favourable course; two cases received initial treatment with oral prednisone continued of oral propanolol in rising pattern up to 2 mg/kg/day, Obtaining both the detention of the tumour growth and regression of the lesion, with very good tolerance. A 7-year-old patient has been treated with colouring pulse laser for her residual lesions. When we see a segmental facial hemangioma we must perform a wide diagnostic study in order to discard a PHACES syndrome. Multidisciplinar approach to the patient by a wide expert's group gets an earlier diagnose and improves the outcome. Propranolol is a promising therapeutic alternative.

[Mechanism of losartan suppressing vascular calcification in rat aortic artery].

PubMed

Shao, Juan; Wu, Panfeng; Wu, Jiliang; Li, Mincai

2016-08-01

Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process.

Gastroschisis, destructive brain lesions, and placental infarction in the second trimester suggest a vascular pathogenesis.

PubMed

Folkerth, Rebecca D; Habbe, Donald M; Boyd, Theonia K; McMillan, Kristin; Gromer, Jessica; Sens, Mary Ann; Elliott, Amy J

2013-01-01

The cause and pathogenesis of gastroschisis are uncertain. We report the autopsy and placental pathology of a stillbirth at 20 gestational weeks, in which gastroschisis was accompanied by destructive lesions in the cerebral cortex and brainstem, as well as cardiac calcification, consistent with ischemic injury during the 2nd trimester. An important potential underlying mechanism explaining the fetal abnormalities is the presence of infarcts in the placenta, indicative at this gestational age of maternal vascular underperfusion. The association of gastroschisis with ischemic lesions in the brain, heart, and placenta in this case supports the concept that gastroschisis, at least in some instances, may result from vascular event(s) causing disruption of the fetal abdominal wall and resulting in the extrusion of the abdominal organs, as well as hypoxic-ischemic brain and cardiac injury.

Plant development. Integration of growth and patterning during vascular tissue formation in Arabidopsis.

PubMed

De Rybel, Bert; Adibi, Milad; Breda, Alice S; Wendrich, Jos R; Smit, Margot E; Novák, Ondřej; Yamaguchi, Nobutoshi; Yoshida, Saiko; Van Isterdael, Gert; Palovaara, Joakim; Nijsse, Bart; Boekschoten, Mark V; Hooiveld, Guido; Beeckman, Tom; Wagner, Doris; Ljung, Karin; Fleck, Christian; Weijers, Dolf

2014-08-08

Coordination of cell division and pattern formation is central to tissue and organ development, particularly in plants where walls prevent cell migration. Auxin and cytokinin are both critical for division and patterning, but it is unknown how these hormones converge upon tissue development. We identify a genetic network that reinforces an early embryonic bias in auxin distribution to create a local, nonresponding cytokinin source within the root vascular tissue. Experimental and theoretical evidence shows that these cells act as a tissue organizer by positioning the domain of oriented cell divisions. We further demonstrate that the auxin-cytokinin interaction acts as a spatial incoherent feed-forward loop, which is essential to generate distinct hormonal response zones, thus establishing a stable pattern within a growing vascular tissue. Copyright © 2014, American Association for the Advancement of Science.

Towards the therapeutic use of vascular smooth muscle progenitor cells.

PubMed

Merkulova-Rainon, Tatyana; Broquères-You, Dong; Kubis, Nathalie; Silvestre, Jean-Sébastien; Lévy, Bernard I

2012-07-15

Recent advances in the development of alternative proangiogenic and revascularization processes, including recombinant protein delivery, gene therapy, and cell therapy, hold the promise of greater efficacy in the management of cardiovascular disease in the coming years. In particular, vascular progenitor cell-based strategies have emerged as an efficient treatment approach to promote vessel formation and repair and to improve tissue perfusion. During the past decade, considerable progress has been achieved in understanding therapeutic properties of endothelial progenitor cells, while the therapeutic potential of vascular smooth muscle progenitor cells (SMPC) has only recently been explored; the number of the circulating SMPC being correlated with cardiovascular health. Several endogenous SMPC populations with varying phenotypes have been identified and characterized in the peripheral blood, bone marrow, and vascular wall. While the phenotypic entity of vascular SMPC is not fully defined and remains an evolving area of research, SMPC are increasingly recognized to play a special role in cardiovascular biology. In this review, we describe the current approaches used to define vascular SMPC. We further summarize the data on phenotype and functional properties of SMPC from various sources in adults. Finally, we discuss the role of SMPC in cardiovascular disease, including the contribution of SMPC to intimal proliferation, angiogenesis, and atherosclerotic plaque instability as well as the benefits resulting from the therapeutic use of SMPC.

Anatomic vascular phantom for the verification of MRA and XRA visualization and fusion

NASA Astrophysics Data System (ADS)

Mankovich, Nicholas J.; Lambert, Timothy; Zrimec, Tatjana; Hiller, John B.

1995-05-01

A project is underway to develop automated methods of fusing cerebral magnetic resonance angiography (MRA) and x-ray angiography (XRA) for creating accurate visualizations used in planning treatment of vascular disease. We have developed a vascular phantom suitable for testing segmentation and fusion algorithms with either derived images (psuedo-MRA/psuedo-XRA) or actual MRA or XRA image sequences. The initial unilateral arterial phantom design, based on normal human anatomy, contains 48 tapering vascular segments with lumen diameters from 2.5 millimeter to 0.25 millimeter. The initial phantom used rapid prototyping technology (stereolithography) with a 0.9 millimeter vessel wall fabricated in an ultraviolet-cured plastic. The model fabrication resulted in a hollow vessel model comprising the internal carotid artery, the ophthalmic artery, and the proximal segments of the anterior, middle, and posterior cerebral arteries. The complete model was fabricated but the model's lumen could not be cleared for vessels with less than 1 millimeter diameter. Measurements of selected vascular outer diameters as judged against the CAD specification showed an accuracy of 0.14 mm and precision (standard deviation) of 0.15 mm. The plastic vascular model produced provides a fixed geometric framework for the evaluation of imaging protocols and the development of algorithms for both segmentation and fusion.

[The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

PubMed

Fischer, Tamás

2015-03-01

The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

[Histological structure of the trabecular meshwork in the eyeball: challenging the traditional concept and preliminary findings in rabbits, rats and mice].

PubMed

Shi, Yun; Zhou, Fan-Qi; Luo, Zhou-Cai; Chen, Ying-Hua; Chen, Yu; Dong, Wei-Ren

2017-10-20

To verify that the trabecular meshwork (TM) in the wall of the eyeball consists of smooth muscle fibers instead of collagen fibers or endothelial cells. Eighteen fresh eyeballs from 3 rabbits, 3 SD rats and 3 mice were sectioned along the sagittal plane and sliced after paraffin embedding for HE staining, VG staining, Masson staining, α-SMA immunohistochemistry or CD31 immunohistochemistry. These slices were observed under microscope and the structure of the TM was compared with those of scleral collagen fibers, ciliary muscles and endothelial cells. HE staining of the eyeball slices from the 3 animal species resulted in purplish red staining of the TM, which was highly consistent with ciliary muscle fibers. The cell?like structures on the surface of the TM were not clearly outlined, with flat nuclei showing a dark purple staining; these structures did not show obvious boundaries from the TM. Ciliary muscle fibers, which were smooth muscle cells in nature, were aligned in bundles in various directions. The longitudinally sectioned cells were flat and contained purplish cytoplasm and highly flattened nuclei. Scleral collagen fibers were stained dark red with a few fibroblasts sandwiched among them. The long axis of the fibroblasts was in parallel with that of the collagen fibers. The outline of the fibroblast was not clear and the nucleus was flat in dark blue. The vascular endothelial cells presented with different morphologies and contained light purplish cytoplasm and dark nuclei, protruding into the vascular cavity. VG staining of the TM revealed a pale red filamentous structure, and the collagen fibers were stained bright red. Masson staining of the TM showed a reticular structure consisting mainly of dark red fibers intermingled with thin green fibers. Scleral collagen fibers presented with a cord?like green wavy structure. The endothelial cells were green and flat, while the ciliary smooth muscle fibers were purple. In immunohistochemistry for α?SMA, the TM and the ciliary smooth muscle fibers showed a strong positivity in the cytoplasm, while the scleral collagen fibers and vascular endothelial cells showed negative staining; immunohistochemistry for CD31 showed no obvious positive staining in the TM, collagen fibers or ciliary smooth muscle cells from all the animals in spite of slight differences among them. The TM consists mainly of smooth muscle fibers with a thin layer of peripheral endomysium without endothelial cells.

A study of the native cell wall structures of the marine alga Ventricaria ventricosa (Siphonocladales, Chlorophyceae) using atomic force microscopy.

PubMed

Eslick, Enid M; Beilby, Mary J; Moon, Anthony R

2014-04-01

A substantial proportion of the architecture of the plant cell wall remains unknown with a few cell wall models being proposed. Moreover, even less is known about the green algal cell wall. Techniques that allow direct visualization of the cell wall in as near to its native state are of importance in unravelling the spatial arrangement of cell wall structures and hence in the development of cell wall models. Atomic force microscopy (AFM) was used to image the native cell wall of living cells of Ventricaria ventricosa (V. ventricosa) at high resolution under physiological conditions. The cell wall polymers were identified mainly qualitatively via their structural appearance. The cellulose microfibrils (CMFs) were easily recognizable and the imaging results indicate that the V. ventricosa cell wall has a cross-fibrillar structure throughout. We found the native wall to be abundant in matrix polysaccharides existing in different curing states. The soft phase matrix polysaccharides susceptible by the AFM scanning tip existed as a glutinous fibrillar meshwork, possibly incorporating both the pectic- and hemicellulosic-type substances. The hard phase matrix producing clearer images, revealed coiled fibrillar structures associated with CMFs, sometimes being resolved as globular structures by the AFM tip. The coiling fibrillar structures were also seen in the images of isolated cell wall fragments. The mucilaginous component of the wall was discernible from the gelatinous cell wall matrix as it formed microstructural domains over the surface. AFM has been successful in imaging the native cell wall and revealing novel findings such as the 'coiling fibrillar structures' and cell wall components which have previously not been seen, that is, the gelatinous matrix phase.

Acute effects of pulsed-laser irradiation on the arterial wall

NASA Astrophysics Data System (ADS)

Nakamura, Fumitaka; Kvasnicka, Jan; Lu, Hanjiang; Geschwind, Herbert J.; Levame, Micheline; Bousbaa, Hassan; Lange, Francoise

1992-08-01

Pulsed laser coronary angioplasty with an excimer or a holmium-yttrium-aluminum-garnet (Ho:YAG) laser may become an alternative treatment for patients with coronary artery disease. However, little is known about its acute consequences on the normal arterial wall. This study was designed to examine the acute histologic consequences of these two pulsed lasers on the arterial wall of normal iliac arteries in rabbits. Irradiation with each laser was performed in 15 normal iliac sites on eight male New Zealand white rabbits. The excimer laser was operated at 308 nm, 25 Hz, 50 mJ/mm2/pulse, and 135 nsec/pulse and the Ho:YAG laser was operated at 2.1 micrometers , 3/5 Hz, 400 mJ/pulse, and 250 microsecond(s) ec/pulse. The excimer and Ho:YAG laser were coupled into a multifiber wire-guided catheter of 1.4 and 1.5 mm diameter, respectively. The sites irradiated with excimer or Ho:YAG laser had the same kinds of histologic features, consisting of exfoliation of the endothelium, disorganization of internal elastic lamina, localized necrosis of vascular smooth muscle cells, and fissures in the medial layer. However, the sites irradiated with excimer laser had lower grading scores than those irradiated with Ho:YAG laser (p < 0.05). Laser irradiation with excimer or Ho:YAG laser of normal arteries results in localized mechanical vascular injury.

The effect of in-plane arterial curvature on blood flow and oxygen transport in arterio-venous fistulae

NASA Astrophysics Data System (ADS)

Iori, F.; Grechy, L.; Corbett, R. W.; Gedroyc, W.; Duncan, N.; Caro, C. G.; Vincent, P. E.

2015-03-01

Arterio-Venous Fistulae (AVF) are the preferred method of vascular access for patients with end stage renal disease who need hemodialysis. In this study, simulations of blood flow and oxygen transport were undertaken in various idealized AVF configurations. The objective of the study was to understand how arterial curvature affects blood flow and oxygen transport patterns within AVF, with a focus on how curvature alters metrics known to correlate with vascular pathology such as Intimal Hyperplasia (IH). If one subscribes to the hypothesis that unsteady flow causes IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto the outer-curvature of a curved artery. However, if one subscribes to the hypothesis that low wall shear stress and/or low lumen-to-wall oxygen flux (leading to wall hypoxia) cause IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto a straight artery, or the inner-curvature of a curved artery. We note that the recommendations are incompatible—highlighting the importance of ascertaining the exact mechanisms underlying development of IH in AVF. Nonetheless, the results clearly illustrate the important role played by arterial curvature in determining AVF hemodynamics, which to our knowledge has been overlooked in all previous studies.

The development of a combined b-mode, ARFI, and spectral Doppler ultrasound imaging system for investigating cardiovascular stiffness and hemodynamics

NASA Astrophysics Data System (ADS)

Doherty, Joshua R.; Dumont, Douglas M.; Trahey, Gregg E.

2011-03-01

The progression of atherosclerotic disease, caused by the formation of plaques within arteries, is a complex process believed to be a function of the localized mechanical properties and hemodynamic loading associated with the arterial wall. It is hypothesized that measurements of vascular stiffness and wall-shear rate (WSR) may provide important information regarding vascular remodeling, endothelial function, and the growth of soft-lipid filled plaques that could help a clinician better diagnose a patient's risk of clinical events such as stroke. To that end, the approach taken in this work was to combine conventional B-mode, Acoustic Radiation Force Impulse (ARFI), Shear Wave Elasticity Imaging (SWEI), and spectral Doppler techniques into a single imaging system capable of simultaneously measuring the tissue displacements and WSR throughout the cardiac cycle and over several heartbeats. Implemented on a conventional scanner, the carotid arteries of human subjects were scanned to demonstrate the initial in vivo feasibility of the method. Two non-invasive ultrasound based imaging methods, SAD-SWEI and SAD-Gated Imaging, were developed that measure ARF-induced on-axis tissue displacements, off-axis transverse wave velocities, and WSR throughout the cardiac cycle. Human carotid artery scans were performed in vivo on 5 healthy subjects. Statistical differences were observed in both on-axis proximal wall displacements and transverse wave velocities during diastole compared to systole.

Nonlinear analysis of aortic flow in living dogs.

NASA Technical Reports Server (NTRS)

Ling, S. C.; Atabek, H. B.; Letzing, W. G.; Patel, D. J.

1973-01-01

A nonlinear theory which considered the convective accelerations of blood and the nonlinear elastic behavior and taper angle of the vascular wall was used to study the nature of blood flow in the descending thoracic aorta of living dogs under a wide range of pressures and flows. Velocity profiles, wall friction, and discharge waves were predicted from locally measured input data about the pressure-gradient wave and arterial distention. The results indicated that a major part of the mean pressure gradient was balanced by convective accelerations; the theory, which took this factor into account, predicted the correct velocity distributions and flow waves.

Impact of the shape of the implantable ports on their efficiency of flow (injection and flushing)

PubMed Central

Guiffant, Gérard; Flaud, Patrice; Durussel, Jean Jacques; Merckx, Jacques

2014-01-01

Now widely used, totally implantable venous access devices allow mid- and long-term, frequent, repeated, or continuous injection of therapeutic products by vascular, cavitary, or perineural access. The effective flushing of these devices is a key factor that ensures their long-lasting use. We present experimental results and a numerical simulation to demonstrate that the implementation of rounded edge wall cavities improves flushing efficiency. We use the same approaches to suggest that the deposit amount may be reduced by the use of rounded edge wall cavities. PMID:25258561

NADPH Oxidases in Vascular Pathology

PubMed Central

Konior, Anna; Schramm, Agata; Czesnikiewicz-Guzik, Marta

2014-01-01

Abstract Significance: Reactive oxygen species (ROS) play a critical role in vascular disease. While there are many possible sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play a central role. They are a source of “kindling radicals,” which affect other enzymes, such as nitric oxide synthase endothelial nitric oxide synthase or xanthine oxidase. This is important, as risk factors for atherosclerosis (hypertension, diabetes, hypercholesterolemia, and smoking) regulate the expression and activity of NADPH oxidases in the vessel wall. Recent Advances: There are seven isoforms in mammals: Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2. Nox1, Nox2, Nox4, and Nox5 are expressed in endothelium, vascular smooth muscle cells, fibroblasts, or perivascular adipocytes. Other homologues have not been found or are expressed at very low levels; their roles have not been established. Nox1/Nox2 promote the development of endothelial dysfunction, hypertension, and inflammation. Nox4 may have a role in protecting the vasculature during stress; however, when its activity is increased, it may be detrimental. Calcium-dependent Nox5 has been implicated in oxidative damage in human atherosclerosis. Critical Issues: NADPH oxidase-derived ROS play a role in vascular pathology as well as in the maintenance of normal physiological vascular function. We also discuss recently elucidated mechanisms such as the role of NADPH oxidases in vascular protection, vascular inflammation, pulmonary hypertension, tumor angiogenesis, and central nervous system regulation of vascular function and hypertension. Future Directions: Understanding the role of individual oxidases and interactions between homologues in vascular disease is critical for efficient pharmacological regulation of vascular NADPH oxidases in both the laboratory and clinical practice. Antioxid. Redox Signal. 20, 2794–2814. PMID:24180474

Structural pounding of concrete frame structure with masonry infill wall under seismic loading

NASA Astrophysics Data System (ADS)

Ismail, Rozaina; Hasnan, Mohd Hafizudin; Shamsudin, Nurhanis

2017-10-01

Structural pounding is additional problem than the other harmful damage that may occurs due to the earthquake vibrations. A lot of study has been made by past researcher but most of them did not include the walls. The infill masonry walls are rarely involved analysis of structural systems but it does contribute to earthquake response of the structures. In this research, a comparison between adjacent building of 10-storey and 7-storey concrete frame structure without of masonry infill walls and the same dynamic properties of buildings. The diagonal strut approach is adopted for modeling masonry infill walls. This research also focused on finding critical building separation in order to prevent the adjacent structures from pounding. LUSAS FEA v14.03 software has been used for modeling analyzing the behavior of structures due to seismic loading and the displacement each floor of the building has been taken in order to determine the critical separation distance between the buildings. From the analysis that has been done, it is found that masonry infill walls do affect the structures behavior under seismic load. Structures without masonry infill walls needs more distance between the structures to prevent structural pounding due to higher displacement of the buildings when it sways under seismic load compared to structures with masonry infill walls. This shows that contribution of masonry infill walls to the analysis of structures cannot be neglected.

Morphologic changes in the vein after different numbers of radiofrequency ablation cycles.

PubMed

Shaidakov, Evgeny V; Grigoryan, Arsen G; Korzhevskii, Dmitriy E; Ilyukhin, Evgeny A; Rosukhovski, Dmitriy A; Bulatov, Vasiliy L; Tsarev, Oleg I

2015-10-01

It has not yet been clarified whether it is possible to decrease the percentage of recurrences after radiofrequency (RF) ablation by way of increasing the number of RF ablation cycles. The aim of this study was to assess the morphologic changes in excised vein fragments after different durations of RF ablation exposure. In the first part of the study, we performed a morphologic analysis of eight cases of great saphenous vein (GSV) recanalization 6 months after RF ablation. The second part was performed on a suprafascial segment of the GSV with a length of >22 cm and a minimum diameter of 5 mm in 10 patients, who had given their consent to intraoperative excision of suprafascial GSV segments after RF ablation treatment through four 1-cm-long diametrical cuts. Prior ultrasound analysis had shown an average 6.9-mm diameter of the suprafascial segments. The segment was divided into three 7-cm-long subsegments and one control segment. The first, second, and third segments were treated with three, two, and one RF ablation cycles (ClosureFast; Covidien, Mansfield, Mass), respectively; the control segment was not exposed to RF ablation at all. Morphologic study of 160 sections of the vein (five sections of each segment and 10 control specimens) was carried out. The specimens were dyed with hematoxylin and orcein. The ensuing analysis was performed by an experienced expert with the blind study method (the specimens were numbered without any hint as to the quantity of RF ablation cycles performed on them). The intergroup comparison of the depth of venous wall damage was based on comparison of the coefficient of alteration, which is calculated as the relation of damage depth to thickness of the vein. After one RF ablation cycle, the depth of blurring of the structural elements only on some portions reached the middle of the muscle layer of the wall (coefficient of alteration, α = 26%). After two cycles, blurring of the structural elements on some portions extended to the adventitia (α = 53%). After three cycles, uniform blurring of the structural elements of all layers of the venous wall up to the adventitia was seen (α = 92%). The statistically significant difference in the alteration coefficient, depending on the number of cycles of RF ablation (P < .005), was established. The number of RF ablation cycles has an impact on the depth of vein wall damage. One and two cycles do not cause damage to all layers of the vein wall. Three cycles cause damage to all vein wall layers. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The crosstalk between autonomic nervous system and blood vessels

PubMed Central

Sheng, Yulan; Zhu, Li

2018-01-01

The autonomic nervous system (ANS), comprised of two primary branches, sympathetic and parasympathetic nervous system, plays an essential role in the regulation of vascular wall contractility and tension. The sympathetic and parasympathetic nerves work together to balance the functions of autonomic effector organs. The neurotransmitters released from the varicosities in the ANS can regulate the vascular tone. Norepinephrine (NE), adenosine triphosphate (ATP) and Neuropeptide Y (NPY) function as vasoconstrictors, whereas acetylcholine (Ach) and calcitonin gene-related peptide (CGRP) can mediate vasodilation. On the other hand, vascular factors, such as endothelium-derived relaxing factor nitric oxide (NO), and constriction factor endothelin, play an important role in the autonomic nervous system in physiologic conditions. Endothelial dysfunction and inflammation are associated with the sympathetic nerve activity in the pathological conditions, such as hypertension, heart failure, and diabetes mellitus. The dysfunction of the autonomic nervous system could be a risk factor for vascular diseases and the overactive sympathetic nerve is detrimental to the blood vessel. In this review, we summarize findings concerning the crosstalk between ANS and blood vessels in both physiological and pathological conditions and hope to provide insight into the development of therapeutic interventions of vascular diseases. PMID:29593847

Platelets secrete stromal cell–derived factor 1α and recruit bone marrow–derived progenitor cells to arterial thrombi in vivo

PubMed Central

Massberg, Steffen; Konrad, Ildiko; Schürzinger, Katrin; Lorenz, Michael; Schneider, Simon; Zohlnhoefer, Dietlind; Hoppe, Katharina; Schiemann, Matthias; Kennerknecht, Elisabeth; Sauer, Susanne; Schulz, Christian; Kerstan, Sandra; Rudelius, Martina; Seidl, Stefan; Sorge, Falko; Langer, Harald; Peluso, Mario; Goyal, Pankaj; Vestweber, Dietmar; Emambokus, Nikla R.; Busch, Dirk H.; Frampton, Jon; Gawaz, Meinrad

2006-01-01

The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow–derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin− bone marrow–derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin− bone marrow–derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1α, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury. PMID:16618794

Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo.

PubMed

Massberg, Steffen; Konrad, Ildiko; Schürzinger, Katrin; Lorenz, Michael; Schneider, Simon; Zohlnhoefer, Dietlind; Hoppe, Katharina; Schiemann, Matthias; Kennerknecht, Elisabeth; Sauer, Susanne; Schulz, Christian; Kerstan, Sandra; Rudelius, Martina; Seidl, Stefan; Sorge, Falko; Langer, Harald; Peluso, Mario; Goyal, Pankaj; Vestweber, Dietmar; Emambokus, Nikla R; Busch, Dirk H; Frampton, Jon; Gawaz, Meinrad

2006-05-15

The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.

Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction

PubMed Central

Mikhed, Yuliya; Daiber, Andreas; Steven, Sebastian

2015-01-01

The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS) leads to oxidative stress, loss of nitric oxide (•NO) signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here discuss the importance of different sources of ROS for vascular aging and their contribution to the increased cardiovascular risk in the elderly population with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA. Also the interaction (crosstalk) of mitochondria with nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases is highlighted. Current concepts of vascular aging, consequences for the development of cardiovascular events and the particular role of ROS are evaluated on the basis of cell culture experiments, animal studies and clinical trials. Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging) than for the maximal lifespan. PMID:26184181

Lysyl Oxidase Induces Vascular Oxidative Stress and Contributes to Arterial Stiffness and Abnormal Elastin Structure in Hypertension: Role of p38MAPK.

PubMed

Martínez-Revelles, Sonia; García-Redondo, Ana B; Avendaño, María S; Varona, Saray; Palao, Teresa; Orriols, Mar; Roque, Fernanda R; Fortuño, Ana; Touyz, Rhian M; Martínez-González, Jose; Salaices, Mercedes; Rodríguez, Cristina; Briones, Ana M

2017-09-01

Vascular stiffness, structural elastin abnormalities, and increased oxidative stress are hallmarks of hypertension. Lysyl oxidase (LOX) is an elastin crosslinking enzyme that produces H 2 O 2 as a by-product. We addressed the interplay between LOX, oxidative stress, vessel stiffness, and elastin. Angiotensin II (Ang II)-infused hypertensive mice and spontaneously hypertensive rats (SHR) showed increased vascular LOX expression and stiffness and an abnormal elastin structure. Mice over-expressing LOX in vascular smooth muscle cells (TgLOX) exhibited similar mechanical and elastin alterations to those of hypertensive models. LOX inhibition with β-aminopropionitrile (BAPN) attenuated mechanical and elastin alterations in TgLOX mice, Ang II-infused mice, and SHR. Arteries from TgLOX mice, Ang II-infused mice, and/or SHR exhibited increased vascular H 2 O 2 and O 2 .- levels, NADPH oxidase activity, and/or mitochondrial dysfunction. BAPN prevented the higher oxidative stress in hypertensive models. Treatment of TgLOX and Ang II-infused mice and SHR with the mitochondrial-targeted superoxide dismutase mimetic mito-TEMPO, the antioxidant apocynin, or the H 2 O 2 scavenger polyethylene glycol-conjugated catalase (PEG-catalase) reduced oxidative stress, vascular stiffness, and elastin alterations. Vascular p38 mitogen-activated protein kinase (p38MAPK) activation was increased in Ang II-infused and TgLOX mice and this effect was prevented by BAPN, mito-TEMPO, or PEG-catalase. SB203580, the p38MAPK inhibitor, normalized vessel stiffness and elastin structure in TgLOX mice. We identify LOX as a novel source of vascular reactive oxygen species and a new pathway involved in vascular stiffness and elastin remodeling in hypertension. LOX up-regulation is associated with enhanced oxidative stress that promotes p38MAPK activation, elastin structural alterations, and vascular stiffness. This pathway contributes to vascular abnormalities in hypertension. Antioxid. Redox Signal. 27, 379-397.

Lysyl Oxidase Induces Vascular Oxidative Stress and Contributes to Arterial Stiffness and Abnormal Elastin Structure in Hypertension: Role of p38MAPK

PubMed Central

Martínez-Revelles, Sonia; García-Redondo, Ana B.; Avendaño, María S.; Varona, Saray; Palao, Teresa; Orriols, Mar; Roque, Fernanda R.; Fortuño, Ana; Touyz, Rhian M.; Martínez-González, Jose; Salaices, Mercedes

2017-01-01

Abstract Aims: Vascular stiffness, structural elastin abnormalities, and increased oxidative stress are hallmarks of hypertension. Lysyl oxidase (LOX) is an elastin crosslinking enzyme that produces H2O2 as a by-product. We addressed the interplay between LOX, oxidative stress, vessel stiffness, and elastin. Results: Angiotensin II (Ang II)-infused hypertensive mice and spontaneously hypertensive rats (SHR) showed increased vascular LOX expression and stiffness and an abnormal elastin structure. Mice over-expressing LOX in vascular smooth muscle cells (TgLOX) exhibited similar mechanical and elastin alterations to those of hypertensive models. LOX inhibition with β-aminopropionitrile (BAPN) attenuated mechanical and elastin alterations in TgLOX mice, Ang II-infused mice, and SHR. Arteries from TgLOX mice, Ang II-infused mice, and/or SHR exhibited increased vascular H2O2 and O2.− levels, NADPH oxidase activity, and/or mitochondrial dysfunction. BAPN prevented the higher oxidative stress in hypertensive models. Treatment of TgLOX and Ang II-infused mice and SHR with the mitochondrial-targeted superoxide dismutase mimetic mito-TEMPO, the antioxidant apocynin, or the H2O2 scavenger polyethylene glycol-conjugated catalase (PEG-catalase) reduced oxidative stress, vascular stiffness, and elastin alterations. Vascular p38 mitogen-activated protein kinase (p38MAPK) activation was increased in Ang II-infused and TgLOX mice and this effect was prevented by BAPN, mito-TEMPO, or PEG-catalase. SB203580, the p38MAPK inhibitor, normalized vessel stiffness and elastin structure in TgLOX mice. Innovation: We identify LOX as a novel source of vascular reactive oxygen species and a new pathway involved in vascular stiffness and elastin remodeling in hypertension. Conclusion: LOX up-regulation is associated with enhanced oxidative stress that promotes p38MAPK activation, elastin structural alterations, and vascular stiffness. This pathway contributes to vascular abnormalities in hypertension. Antioxid. Redox Signal. 27, 379–397. PMID:28010122

In Silico Shear and Intramural Stresses are Linked to Aortic Valve Morphology in Dilated Ascending Aorta.

PubMed

Pasta, S; Gentile, G; Raffa, G M; Bellavia, D; Chiarello, G; Liotta, R; Luca, A; Scardulla, C; Pilato, M

2017-08-01

The development of ascending aortic dilatation in patients with bicuspid aortic valve (BAV) is highly variable, and this makes surgical decision strategies particularly challenging. The purpose of this study was to identify new predictors, other than the well established aortic size, that may help to stratify the risk of aortic dilatation in BAV patients. Using fluid-structure interaction analysis, both haemodynamic and structural parameters exerted on the ascending aortic wall of patients with either BAV (n = 21) or tricuspid aortic valve (TAV; n = 13) with comparable age and aortic diameter (42.7 ± 5.3 mm for BAV and 45.4 ± 10.0 mm for TAV) were compared. BAV phenotypes were stratified according to the leaflet fusion pattern and aortic shape. Systolic wall shear stress (WSS) of BAV patients was higher than TAV patients at the sinotubular junction (6.8 ± 3.3 N/m 2 for BAV and 3.9 ± 1.3 N/m 2 for TAV; p = .006) and mid-ascending aorta (9.8 ± 3.3 N/m 2 for BAV and 7.1 ± 2.3 N/m 2 for TAV; p = .040). A statistically significant difference in BAV versus TAV was also observed for the intramural stress along the ascending aorta (e.g., 2.54 × 10 5  ± 0.32 × 10 5  N/m 2 for BAV and 2.04 × 10 5  ± 0.34 × 10 5  N/m 2 for TAV; p < .001) and pressure index (0.329 ± 0.107 for BAV and 0.223 ± 0.139 for TAV; p = .030). Differences in the BAV phenotypes (i.e., BAV type 1 vs. BAV type 2) and aortopathy (i.e., isolated tubular vs. aortic root dilatations) were associated with asymmetric WSS distributions in the right anterior aortic wall and right posterior aortic wall, respectively. These findings suggest that valve mediated haemodynamic and structural parameters may be used to identify which regions of aortic wall are at greater stress and enable the development of a personalised approach for the diagnosis and management of aortic dilatation beyond traditional guidelines. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Blood pressure regulation V: in vivo mechanical properties of precapillary vessels as affected by long-term pressure loading and unloading.

PubMed

Eiken, Ola; Mekjavic, Igor B; Kölegård, Roger

2014-03-01

Recent studies are reviewed, concerning the in vivo wall stiffness of arteries and arterioles in healthy humans, and how these properties adapt to iterative increments or sustained reductions in local intravascular pressure. A novel technique was used, by which arterial and arteriolar stiffness was determined as changes in arterial diameter and flow, respectively, during graded increments in distending pressure in the blood vessels of an arm or a leg. Pressure-induced increases in diameter and flow were smaller in the lower leg than in the arm, indicating greater stiffness in the arteries/arterioles of the leg. A 5-week period of intermittent intravascular pressure elevations in one arm reduced pressure distension and pressure-induced flow in the brachial artery by about 50%. Conversely, prolonged reduction of arterial/arteriolar pressure in the lower body by 5 weeks of sustained horizontal bedrest, induced threefold increases of the pressure-distension and pressure-flow responses in a tibial artery. Thus, the wall stiffness of arteries and arterioles are plastic properties that readily adapt to changes in the prevailing local intravascular pressure. The discussion concerns mechanisms underlying changes in local arterial/arteriolar stiffness as well as whether stiffness is altered by changes in myogenic tone and/or wall structure. As regards implications, regulation of local arterial/arteriolar stiffness may facilitate control of arterial pressure in erect posture and conditions of exaggerated intravascular pressure gradients. That increased intravascular pressure leads to increased arteriolar wall stiffness also supports the notion that local pressure loading may constitute a prime mover in the development of vascular changes in hypertension.

Characterization of Human Torso Vascular Morphometry in Normotensive and Hypotensive Trauma Patients

DTIC Science & Technology

2015-07-01

Aorta Wall Measures Merged for Analysis Landmarks & User-aided Segmentation 5cm Volume...with Centerline Measures AORTA PROCESSING VENA CAVA PROCESSING Basic Morphomics Scan Identification Aorta Centerline Segmented Aorta and Vena...Analysis 49 Data Presentation Aorta  Radius  Popula/on       Normotensive   Hypotensive  

Hydraulic Conductivity of Smooth Muscle Cell-Initiated Arterial Cocultures

PubMed Central

Mathura, Rishi A.; Russell-Puleri, Sparkle; Cancel, Limary M.; Tarbell, John M.

2015-01-01

The purpose of the study was to examine the effects of arterial coculture conditions on the transport properties of several in vitro endothelial cell (EC) – smooth muscle cell (SMC) – porous filter constructs in which SMC were grown to confluence first and then EC were inoculated. This order of culturing simulates the environment of a blood vessel wall after endothelial layer damage due to stenting, vascular grafting or other vascular wall insult. For all coculture configurations examined, we observed that hydraulic conductivity (Lp) values were significantly higher than predicted by a resistances-in-series (RIS) model accounting for the Lp of EC and SMC measured separately. The greatest increases were observed when EC were plated directly on top of a confluent SMC layer without an intervening filter, presumably mediated by direct EC – SMC contacts that were observed under confocal microscopy. The results are the opposite of a previous study that showed Lp was significantly reduced compared to an RIS model when EC were grown to confluency first. The physiological, pathophysiological and tissue engineering implications of these results are discussed. PMID:26265460

Hydraulic Conductivity of Smooth Muscle Cell-Initiated Arterial Cocultures.

PubMed

Mathura, Rishi A; Russell-Puleri, Sparkle; Cancel, Limary M; Tarbell, John M

2016-05-01

The purpose of the study was to examine the effects of arterial coculture conditions on the transport properties of several in vitro endothelial cell (EC)-smooth muscle cell (SMC)-porous filter constructs in which SMC were grown to confluence first and then EC were inoculated. This order of culturing simulates the environment of a blood vessel wall after endothelial layer damage due to stenting, vascular grafting or other vascular wall insult. For all coculture configurations examined, we observed that hydraulic conductivity (L(p)) values were significantly higher than predicted by a resistances-in-series (RIS) model accounting for the L(p) of EC and SMC measured separately. The greatest increases were observed when EC were plated directly on top of a confluent SMC layer without an intervening filter, presumably mediated by direct EC-SMC contacts that were observed under confocal microscopy. The results are the opposite of a previous study that showed L(p) was significantly reduced compared to an RIS model when EC were grown to confluency first. The physiological, pathophysiological and tissue engineering implications of these results are discussed.

Effect of preoperative antiplatelet drugs on vascular prostacyclin synthesis.

PubMed

Karwande, S V; Weksler, B B; Gay, W A; Subramanian, V A

1987-03-01

Patients undergoing aortocoronary bypass using autogenous saphenous veins were randomly divided into three comparable groups. Group 1 (n = 10) acted as a control, Group 2 (n = 14) received 80 mg of aspirin at midnight before the operation, and Group 3 (n = 12) received 80 mg of aspirin and 75 mg of dipyridamole at midnight and an additional 75-mg dose of dipyridamole at 6 AM. The purpose was to determine which regimen would maximally inhibit platelet function without depressing vascular prostacyclin synthesis. Serum thromboxane A2, saphenous vein wall and aortic wall prostacyclin, platelet aggregation, and bleeding time were measured in all patients. None was restarted on a regimen of aspirin or dipyridamole postoperatively. Aspirin alone and in combination with dipyridamole significantly inhibited thromboxane A2 and platelet aggregation in all treated patients but spared venous prostacyclin synthesis. Aortic prostacyclin synthesis was partially inhibited in both treated groups. Chest tube drainage was comparable in all three groups. These results indicate that the combination of aspirin and dipyridamole offers no measurable advantage over aspirin alone in the perioperative period.

In Vitro Generation of Vascular Wall-Resident Multipotent Stem Cells of Mesenchymal Nature from Murine Induced Pluripotent Stem Cells.

PubMed

Steens, Jennifer; Zuk, Melanie; Benchellal, Mohamed; Bornemann, Lea; Teichweyde, Nadine; Hess, Julia; Unger, Kristian; Görgens, André; Klump, Hannes; Klein, Diana

2017-04-11

The vascular wall (VW) serves as a niche for mesenchymal stem cells (MSCs). In general, tissue-specific stem cells differentiate mainly to the tissue type from which they derive, indicating that there is a certain code or priming within the cells as determined by the tissue of origin. Here we report the in vitro generation of VW-typical MSCs from induced pluripotent stem cells (iPSCs), based on a VW-MSC-specific gene code. Using a lentiviral vector expressing the so-called Yamanaka factors, we reprogrammed tail dermal fibroblasts from transgenic mice containing the GFP gene integrated into the Nestin-locus (NEST-iPSCs) to facilitate lineage tracing after subsequent MSC differentiation. A lentiviral vector expressing a small set of recently identified human VW-MSC-specific HOX genes then induced MSC differentiation. This direct programming approach successfully mediated the generation of VW-typical MSCs with classical MSC characteristics, both in vitro and in vivo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.