Notch Signaling in Vascular Smooth Muscle Cells

PubMed Central

Baeten, J.T.; Lilly, B.

2018-01-01

The Notch signaling pathway is a highly conserved pathway involved in cell fate determination in embryonic development and also functions in the regulation of physiological processes in several systems. It plays an especially important role in vascular development and physiology by influencing angiogenesis, vessel patterning, arterial/venous specification, and vascular smooth muscle biology. Aberrant or dysregulated Notch signaling is the cause of or a contributing factor to many vascular disorders, including inherited vascular diseases, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with degeneration of the smooth muscle layer in cerebral arteries. Like most signaling pathways, the Notch signaling axis is influenced by complex interactions with mediators of other signaling pathways. This complexity is also compounded by different members of the Notch family having both overlapping and unique functions. Thus, it is vital to fully understand the roles and interactions of each Notch family member in order to effectively and specifically target their exact contributions to vascular disease. In this chapter, we will review the Notch signaling pathway in vascular smooth muscle cells as it relates to vascular development and human disease. PMID:28212801

Comparison of tissue processing methods for microvascular visualization in axolotls.

PubMed

Montoro, Rodrigo; Dickie, Renee

2017-01-01

The vascular system, the pipeline for oxygen and nutrient delivery to tissues, is essential for vertebrate development, growth, injury repair, and regeneration. With their capacity to regenerate entire appendages throughout their lifespan, axolotls are an unparalleled model for vertebrate regeneration, but they lack many of the molecular tools that facilitate vascular imaging in other animal models. The determination of vascular metrics requires high quality image data for the discrimination of vessels from background tissue. Quantification of the vasculature using perfused, cleared specimens is well-established in mammalian systems, but has not been widely employed in amphibians. The objective of this study was to optimize tissue preparation methods for the visualization of the microvascular network in axolotls, providing a basis for the quantification of regenerative angiogenesis. To accomplish this aim, we performed intracardiac perfusion of pigment-based contrast agents and evaluated aqueous and non-aqueous clearing techniques. The methods were verified by comparing the quality of the vascular images and the observable vascular density across treatment groups. Simple and inexpensive, these tissue processing techniques will be of use in studies assessing vascular growth and remodeling within the context of regeneration. Advantages of this method include: •Higher contrast of the vasculature within the 3D context of the surrounding tissue •Enhanced detection of microvasculature facilitating vascular quantification •Compatibility with other labeling techniques.

Aging, Atherosclerosis, and IGF-1

PubMed Central

Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung

2012-01-01

Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1–induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging. PMID:22491965

Lean manufacturing and Toyota Production System terminology applied to the procurement of vascular stents in interventional radiology.

PubMed

de Bucourt, Maximilian; Busse, Reinhard; Güttler, Felix; Wintzer, Christian; Collettini, Federico; Kloeters, Christian; Hamm, Bernd; Teichgräber, Ulf K

2011-08-01

OBJECTIVES: To apply the economic terminology of lean manufacturing and the Toyota Production System to the procurement of vascular stents in interventional radiology. METHODS: The economic- and process-driven terminology of lean manufacturing and the Toyota Production System is first presented, including information and product flow as well as value stream mapping (VSM), and then applied to an interdisciplinary setting of physicians, nurses and technicians from different medical departments to identify wastes in the process of endovascular stent procurement in interventional radiology. RESULTS: Using the so-called seven wastes approach of the Toyota Production System (waste of overproducing, waiting, transport, processing, inventory, motion and waste of defects and spoilage) as well as further waste characteristics (gross waste, process and method waste, and micro waste), wastes in the process of endovascular stent procurement in interventional radiology were identified and eliminated to create an overall smoother process from the procurement as well as from the medical perspective. CONCLUSION: Economic terminology of lean manufacturing and the Toyota Production System, especially VSM, can be used to visualise and better understand processes in the procurement of vascular stents in interventional radiology from an economic point of view.

New Insights into Dialysis Vascular Access: What Is the Optimal Vascular Access Type and Timing of Access Creation in CKD and Dialysis Patients?

PubMed

Woo, Karen; Lok, Charmaine E

2016-08-08

Optimal vascular access planning begins when the patient is in the predialysis stages of CKD. The choice of optimal vascular access for an individual patient and determining timing of access creation are dependent on a multitude of factors that can vary widely with each patient, including demographics, comorbidities, anatomy, and personal preferences. It is important to consider every patient's ESRD life plan (hence, their overall dialysis access life plan for every vascular access creation or placement). Optimal access type and timing of access creation are also influenced by factors external to the patient, such as surgeon experience and processes of care. In this review, we will discuss the key determinants in optimal access type and timing of access creation for upper extremity arteriovenous fistulas and grafts. Copyright © 2016 by the American Society of Nephrology.

Exercise training and cardiometabolic diseases: focus on the vascular system.

PubMed

Roque, Fernanda R; Hernanz, Raquel; Salaices, Mercedes; Briones, Ana M

2013-06-01

The regular practice of physical activity is a well-recommended strategy for the prevention and treatment of several cardiovascular and metabolic diseases. Physical exercise prevents the progression of vascular diseases and reduces cardiovascular morbidity and mortality. Exercise training also ameliorates vascular changes including endothelial dysfunction and arterial remodeling and stiffness, usually present in type 2 diabetes, obesity, hypertension and metabolic syndrome. Common to these diseases is excessive oxidative stress, which plays an important role in the processes underlying vascular changes. At the vascular level, exercise training improves the redox state and consequently NO availability. Moreover, growing evidence indicates that other mediators such as prostanoids might be involved in the beneficial effects of exercise. The purpose of this review is to update recent findings describing the adaptation response induced by exercise in cardiovascular and metabolic diseases, focusing more specifically on the beneficial effects of exercise in the vasculature and the underlying mechanisms.

Biomaterial-mediated strategies targeting vascularization for bone repair.

PubMed

García, José R; García, Andrés J

2016-04-01

Repair of non-healing bone defects through tissue engineering strategies remains a challenging feat in the clinic due to the aversive microenvironment surrounding the injured tissue. The vascular damage that occurs following a bone injury causes extreme ischemia and a loss of circulating cells that contribute to regeneration. Tissue-engineered constructs aimed at regenerating the injured bone suffer from complications based on the slow progression of endogenous vascular repair and often fail at bridging the bone defect. To that end, various strategies have been explored to increase blood vessel regeneration within defects to facilitate both tissue-engineered and natural repair processes. Developments that induce robust vascularization will need to consolidate various parameters including optimization of embedded therapeutics, scaffold characteristics, and successful integration between the construct and the biological tissue. This review provides an overview of current strategies as well as new developments in engineering biomaterials to induce reparation of a functional vascular supply in the context of bone repair.

Aging and vascular endothelial function in humans

PubMed Central

SEALS, Douglas R.; JABLONSKI, Kristen L.; DONATO, Anthony J.

2012-01-01

Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging. PMID:21244363

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.

Cell-derived microparticles in haemostasis and vascular medicine.

PubMed

Burnier, Laurent; Fontana, Pierre; Kwak, Brenda R; Angelillo-Scherrer, Anne

2009-03-01

Considerable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets - the main source of microparticles - but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.

Small vessel disease, neurovascular regulation and cognitive impairment: post-mortem studies reveal a complex relationship, still poorly understood.

PubMed

Love, Seth; Miners, J Scott

2017-07-15

The contribution of vascular disease to cognitive impairment is under-recognized and the pathogenesis is poorly understood. This information gap has multiple causes, including a lack of post-mortem validation of clinical diagnoses of vascular cognitive impairment (VCI) or vascular dementia (VaD), the exclusion of cases with concomitant neurodegenerative disease when diagnosing VCI/VaD, and a lack of standardization of neuropathological assessment protocols for vascular disease. Other contributors include a focus on end-stage destructive lesions to the exclusion of more subtle types of diffuse brain injury, on structural abnormalities of arteries and arterioles to the exclusion of non-structural abnormalities and capillary damage, and the use of post-mortem sampling strategies that are biased towards the identification of neurodegenerative pathologies. Recent studies have demonstrated the value of detailed neuropathology in characterizing vascular contributions to cognitive impairment (e.g. in diabetes), and highlight the importance of diffuse white matter changes, capillary damage and vasoregulatory abnormalities in VCI/VaD. The use of standardized, evidence-based post-mortem assessment protocols and the inclusion of biochemical as well as morphological methods in neuropathological studies should improve the accuracy of determination of the contribution of vascular disease to cognitive impairment and clarify the relative contribution of different pathogenic processes to the tissue damage. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Node-controlled allocation of mineral elements in Poaceae.

PubMed

Yamaji, Naoki; Ma, Jian Feng

2017-10-01

Mineral elements taken up by the roots will be delivered to different organs and tissues depending on their requirements. In Poaceae, this selective distribution is mainly mediated in the nodes, which have highly developed and fully organized vascular systems. Inter-vascular transfer of mineral elements from enlarged vascular bundles to diffuse vascular bundles is required for their preferential distribution to developing tissues and reproductive organs. A number of transporters involved in this inter-vascular transfer processes have been identified mainly in rice. They are localized at the different cell layers and form an efficient machinery within the node. Furthermore, some these transporters show rapid response to the environmental changes of mineral elements at the protein level. In addition to the node-based transporters, distinct nodal structures including enlarged xylem area, folded plasma membrane of xylem transfer cells and presence of an apoplastic barrier are also required for the efficient inter-vascular transfer. Manipulation of node-based transporters will provide a novel breeding target to improve nutrient use efficiency, productivity, nutritional value and safety in cereal crops. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lean principles optimize on-time vascular surgery operating room starts and decrease resident work hours.

PubMed

Warner, Courtney J; Walsh, Daniel B; Horvath, Alexander J; Walsh, Teri R; Herrick, Daniel P; Prentiss, Steven J; Powell, Richard J

2013-11-01

Lean process improvement techniques are used in industry to improve efficiency and quality while controlling costs. These techniques are less commonly applied in health care. This study assessed the effectiveness of Lean principles on first case on-time operating room starts and quantified effects on resident work hours. Standard process improvement techniques (DMAIC methodology: define, measure, analyze, improve, control) were used to identify causes of delayed vascular surgery first case starts. Value stream maps and process flow diagrams were created. Process data were analyzed with Pareto and control charts. High-yield changes were identified and simulated in computer and live settings prior to implementation. The primary outcome measure was the proportion of on-time first case starts; secondary outcomes included hospital costs, resident rounding time, and work hours. Data were compared with existing benchmarks. Prior to implementation, 39% of first cases started on time. Process mapping identified late resident arrival in preoperative holding as a cause of delayed first case starts. Resident rounding process inefficiencies were identified and changed through the use of checklists, standardization, and elimination of nonvalue-added activity. Following implementation of process improvements, first case on-time starts improved to 71% at 6 weeks (P = .002). Improvement was sustained with an 86% on-time rate at 1 year (P < .001). Resident rounding time was reduced by 33% (from 70 to 47 minutes). At 9 weeks following implementation, these changes generated an opportunity cost potential of $12,582. Use of Lean principles allowed rapid identification and implementation of perioperative process changes that improved efficiency and resulted in significant cost savings. This improvement was sustained at 1 year. Downstream effects included improved resident efficiency with decreased work hours. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage

PubMed Central

St John, Ashley L; Rathore, Abhay PS; Raghavan, Bhuvanakantham; Ng, Mah-Lee; Abraham, Soman N

2013-01-01

Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infection, and we show that this elevates systemic levels of their vasoactive products, including chymase, and promotes vascular leakage. Treatment of infected animals with MC-stabilizing drugs or a leukotriene receptor antagonist restores vascular integrity during experimental DENV infection. Validation of these findings using human clinical samples revealed a direct correlation between MC activation and DENV disease severity. In humans, the MC-specific product, chymase, is a predictive biomarker distinguishing dengue fever (DF) and dengue hemorrhagic fever (DHF). Additionally, our findings reveal MCs as potential therapeutic targets to prevent DENV-induced vasculopathy, suggesting MC-stabilizing drugs should be evaluated for their effectiveness in improving disease outcomes during viral hemorrhagic fevers. DOI: http://dx.doi.org/10.7554/eLife.00481.001 PMID:23638300

Features and selection of vascular access devices.

PubMed

Sansivero, Gail Egan

2010-05-01

To review venous anatomy and physiology, discuss assessment parameters before vascular access device (VAD) placement, and review VAD options. Journal articles, personal experience. A number of VAD options are available in clinical practice. Access planning should include comprehensive assessment, with attention to patient participation in the planning and selection process. Careful consideration should be given to long-term access needs and preservation of access sites. Oncology nurses are uniquely suited to perform a key role in VAD planning and placement. With knowledge of infusion therapy, anatomy and physiology, device options, and community resources, nurses can be key leaders in preserving vascular access and improving the safety and comfort of infusion therapy. Copyright 2010 Elsevier Inc. All rights reserved.

Systemic and localized scleroderma.

PubMed

Chung, Lorinda; Lin, Jan; Furst, Daniel E; Fiorentino, David

2006-01-01

Sclerosing conditions of the skin are manifested by a full spectrum of presentations that includes skin-limited forms as well as those which can involve internal organs and result in death. At this point, we are just beginning to understand the mechanisms of tissue fibrosis, and it is likely that the fibrotic processes are a heterogeneous group of disorders in which perturbation of multiple molecular pathways, including vascular and immunologically mediated pathways, can lead to fibrosis. We now have some moderately effective therapies for vascular aspects of systemic sclerosis (eg, bosentan for pulmonary arterial hypertension, calcium-channel blockers for Raynaud's, or angiotensin-converting enzyme inhibitors for renal crisis). We also are beginning to find treatments interrupting the immunologic pathways that manifest as systemic sclerosis (eg, methotrexate for the skin or cyclophosphamide for the lungs). The basic process of fibrosis, however, awaits proven, effective therapy.

Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.

PubMed

Ringvold, H C; Khalil, R A

2017-01-01

Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca 2+ -dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca 2+ -dependent α, β, and γ, novel Ca 2+ -independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs. Activated PKC phosphorylates different substrates including ion channels, pumps, and nuclear proteins. PKC also phosphorylates CPI-17 leading to inhibition of MLC phosphatase, increased MLC phosphorylation, and enhanced VSM contraction. PKC could also initiate a cascade of protein kinases leading to phosphorylation of the actin-binding proteins calponin and caldesmon, increased actin-myosin interaction, and VSM contraction. Increased PKC activity has been associated with vascular disorders including ischemia-reperfusion injury, coronary artery disease, hypertension, and diabetic vasculopathy. PKC inhibitors could test the role of PKC in different systems and could reduce PKC hyperactivity in vascular disorders. First-generation PKC inhibitors such as staurosporine and chelerythrine are not very specific. Isoform-specific PKC inhibitors such as ruboxistaurin have been tested in clinical trials. Target delivery of PKC pseudosubstrate inhibitory peptides and PKC siRNA may be useful in localized vascular disease. Further studies of PKC and its role in VSM should help design isoform-specific PKC modulators that are experimentally potent and clinically safe to target PKC in vascular disease. © 2017 Elsevier Inc. All rights reserved.

Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction

PubMed Central

Barton, Matthias; Baretella, Oliver; Meyer, Matthias R

2012-01-01

Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis-related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium-derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, ‘premature’ vascular aging. Here, we will review some of the pathomechanisms involved in obesity-related activation of endothelium-dependent vasoconstriction, the clinical relevance of obesity-associated vascular risk, and therapeutic interventions using ‘endothelial therapy’ aiming at maintaining or restoring vascular endothelial health. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21557734

Histological and morphometric analyses for rat carotid balloon injury model.

PubMed

Tulis, David A

2007-01-01

Experiments aimed at analyzing the response of blood vessels to mechanical injury and ensuing remodeling responses often employ the highly characterized carotid artery balloon injury model in laboratory rats. This approach utilizes luminal insertion of a balloon embolectomy catheter into the common carotid artery with inflation and withdrawal resulting in an injury characterized by vascular endothelial cell (EC) denudation and medial wall distension. The adaptive response to this injury is typified by robust vascular smooth muscle cell (SMC) replication and migration, SMC apoptosis and necrosis, enhanced synthesis and deposition of extracellular matrix (ECM) components, partial vascular EC regeneration from the border zones, luminal narrowing, and establishment of a neointima in time-dependent fashion. Evaluation of these adaptive responses to blood vessel injury can include acute and longer term qualitative and quantitative measures including expression analyses, activity assays, immunostaining for a plethora of factors and signals, and morphometry of neointima formation and gross mural remodeling. This chapter presents a logical continuation of Chapter 1 that offers details for performing the rat carotid artery balloon injury model in a standard laboratory setting by providing commonly used protocols for performing histological and morphometric analyses in such studies. Moreover, procedures, caveats, and considerations included in this chapter are highly relevant for alternative animal vascular physiology/pathophysiology studies and in particular those related to mechanisms of vascular injury and repair. Included in this chapter are specifics for in situ perfusion-fixation, tissue harvesting and processing for both snap-frozen and paraffin-embedded protocols, specimen embedding and sectioning, slide preparation, several standard histological staining steps, and routine morphological assessment.

Vascular anomalies: classification, imaging characteristics and implications for interventional radiology treatment approaches

PubMed Central

Prajapati, H J S; Martin, L G; Patel, T H

2014-01-01

The term vascular anomaly represents a broad spectrum of vascular pathology, including proliferating vascular tumours and vascular malformations. While the treatment of most vascular anomalies is multifactorial, interventional radiology procedures, including embolic therapy, sclerotherapy and laser coagulation among others, are playing an increasingly important role in vascular anomaly management. This review discusses the diagnosis and treatment of common vascular malformations, with emphasis on the technique, efficacy and complications of different interventional radiology procedures. PMID:24588666

Matrix metalloproteinase inhibitors as investigative tools in the pathogenesis and management of vascular disease.

PubMed

Benjamin, Mina M; Khalil, Raouf A

2012-01-01

Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade various components of the extracellular matrix (ECM). MMPs could also regulate the activity of several non-ECM bioactive substrates and consequently affect different cellular functions. Members of the MMPs family include collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and others. Pro-MMPs are cleaved into active MMPs, which in turn act on various substrates in the ECM and on the cell surface. MMPs play an important role in the regulation of numerous physiological processes including vascular remodeling and angiogenesis. MMPs may also be involved in vascular diseases such as hypertension, atherosclerosis, aortic aneurysm, and varicose veins. MMPs also play a role in the hemodynamic and vascular changes associated with pregnancy and preeclampsia. The role of MMPs is commonly assessed by measuring their gene expression, protein amount, and proteolytic activity using gel zymography. Because there are no specific activators of MMPs, MMP inhibitors are often used to investigate the role of MMPs in different physiologic processes and in the pathogenesis of specific diseases. MMP inhibitors include endogenous tissue inhibitors (TIMPs) and pharmacological inhibitors such as zinc chelators, doxycycline, and marimastat. MMP inhibitors have been evaluated as diagnostic and therapeutic tools in cancer, autoimmune disease, and cardiovascular disease. Although several MMP inhibitors have been synthesized and tested both experimentally and clinically, only one MMP inhibitor, i.e., doxycycline, is currently approved by the Food and Drug Administration. This is mainly due to the undesirable side effects of MMP inhibitors especially on the musculoskeletal system. While most experimental and clinical trials of MMP inhibitors have not demonstrated significant benefits, some trials still showed promising results. With the advent of new genetic and pharmacological tools, disease-specific MMP inhibitors with fewer undesirable effects are being developed and could be useful in the management of vascular disease.

Histological and Morphometric Analyses for Rat Carotid Artery Balloon Injury Studies

PubMed Central

Tulis, David Anthony

2010-01-01

i. Summary Experiments aimed at analyzing the response of blood vessels to mechanical injury and ensuing remodeling responses often employ the highly characterized carotid artery balloon injury model in laboratory rats. This approach utilizes luminal insertion of a balloon embolectomy catheter into the common carotid artery with inflation and withdrawal resulting in an injury characterized by vascular endothelial cell (EC) denudation and medial wall distension. The adaptive response to this injury is typified by robust vascular smooth muscle cell (SMC) replication and migration, SMC apoptosis and necrosis, enhanced synthesis and deposition of extracellular matrix (ECM) components, partial vascular EC regeneration from the border zones, luminal narrowing and establishment of a neointima in time-dependent fashion. Evaluation of these adaptive responses to blood vessel injury can include acute and longer-term qualitative and quantitative measures including expression analyses, activity assays, immunostaining for a plethora of factors and signals, and morphometry of neointima formation and gross mural remodeling. This chapter presents a logical continuation of Chapter    in this series that offers details for performing the rat carotid artery balloon injury model in a standard laboratory setting by providing commonly used protocols for performing histological and morphometric analyses in such studies. Moreover, procedures, caveats, and considerations included in this chapter are highly relevant for alternative animal vascular physiology/pathophysiology studies and in particular those related to mechanisms of vascular injury and repair. Included in this chapter are specifics for in situ perfusion-fixation, tissue harvesting and processing for both snap-frozen and paraffin-embedded protocols, specimen embedding and sectioning, slide preparation, several standard histological staining steps, and routine morphological assessment. Included in Notes are important caveats and considerations for practical use of these methods. PMID:18287663

Hyaline-Vascular Type Castleman's Disease, Sarcoidosis, and Crohns Disease.

PubMed

Gupta, Arjun; Ayyar, Balaji; Zia, Hamid; Chen, Weina; Harris, Samar; Naina, Harris V

2016-06-01

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease.

Stimulation-induced decreases in the diffusion of extra-vascular water in the human visual cortex: a window in time and space on mechanisms of brain water transport and economy.

PubMed

Baslow, Morris H; Hu, Caixia; Guilfoyle, David N

2012-07-01

In a human magnetic resonance diffusion-weighted imaging (DWI) investigation at 3 T and high diffusion sensitivity weighting (b = 1,800 s/mm(2)), which emphasizes the contribution of water in the extra-vascular compartment and minimizes that of the vascular compartment, we observed that visual stimulation with a flashing checkerboard at 8 Hz for a period of 600 s in eight subjects resulted in significant increases in DWI signals (mean +2.70%, range +0.51 to 8.54%). The increases in DWI signals in activated areas of the visual cortex indicated that during stimulation, the apparent diffusion coefficient (ADC) of extra-vascular compartment water decreased. In response to continuous stimulation, DWI signals gradually increased from pre-stimulation controls, leveling off after 400-500 s. During recovery from stimulation, DWI signals gradually decreased, approaching control levels in 300-400 s. In this study, we show for the first time that the effects of visual stimulation on DWI signals in the human visual cortex are cumulative over an extended period of time. We propose that these relatively slow stimulation-induced changes in the ADC of water in the extra-vascular compartment are due to transient changes in the ratio of faster diffusing free water to slower diffusing bound water and reflect brain water transport processes between the vascular and extra-vascular compartments at the cellular level. The nature of these processes including possible roles of the putative glucose water import and N-acetylaspartate water export molecular water pumps in brain function are discussed.

Distinct effects of glucose and glucosamine on vascular endothelial and smooth muscle cells: Evidence for a protective role for glucosamine in atherosclerosis

PubMed Central

Duan, Wenlan; Paka, Latha; Pillarisetti, Sivaram

2005-01-01

Accelerated atherosclerosis is one of the major vascular complications of diabetes. Factors including hyperglycemia and hyperinsulinemia may contribute to accelerated vascular disease. Among the several mechanisms proposed to explain the link between hyperglycemia and vascular dysfunction is the hexosamine pathway, where glucose is converted to glucosamine. Although some animal experiments suggest that glucosamine may mediate insulin resistance, it is not clear whether glucosamine is the mediator of vascular complications associated with hyperglycemia. Several processes may contribute to diabetic atherosclerosis including decreased vascular heparin sulfate proteoglycans (HSPG), increased endothelial permeability and increased smooth muscle cell (SMC) proliferation. In this study, we determined the effects of glucose and glucosamine on endothelial cells and SMCs in vitro and on atherosclerosis in apoE null mice. Incubation of endothelial cells with glucosamine, but not glucose, significantly increased matrix HSPG (perlecan) containing heparin-like sequences. Increased HSPG in endothelial cells was associated with decreased protein transport across endothelial cell monolayers and decreased monocyte binding to subendothelial matrix. Glucose increased SMC proliferation, whereas glucosamine significantly inhibited SMC growth. The antiproliferative effect of glucosamine was mediated via induction of perlecan HSPG. We tested if glucosamine affects atherosclerosis development in apoE-null mice. Glucosamine significantly reduced the atherosclerotic lesion in aortic root. (P < 0.05) These data suggest that macrovascular disease associated with hyperglycemia is unlikely due to glucosamine. In fact, glucosamine by increasing HSPG showed atheroprotective effects. PMID:16207378

What determines blood vessel structure? Genetic prespecification vs. hemodynamics.

PubMed

Jones, Elizabeth A V; le Noble, Ferdinand; Eichmann, Anne

2006-12-01

Vascular network remodeling, angiogenesis, and arteriogenesis play an important role in the pathophysiology of ischemic cardiovascular diseases and cancer. Based on recent studies of vascular network development in the embryo, several novel aspects to angiogenesis have been identified as crucial to generate a functional vascular network. These aspects include specification of arterial and venous identity in vessels and network patterning. In early embryogenesis, vessel identity and positioning are genetically hardwired and involve neural guidance genes expressed in the vascular system. We demonstrated that, during later stages of embryogenesis, blood flow plays a crucial role in regulating vessel identity and network remodeling. The flow-evoked remodeling process is dynamic and involves a high degree of vessel plasticity. The open question in the field is how genetically predetermined processes in vessel identity and patterning balance with the contribution of blood flow in shaping a functional vascular architecture. Although blood flow is essential, it remains unclear to what extent flow is able to act on the developing cardiovascular system. There is significant evidence that mechanical forces created by flowing blood are biologically active within the embryo and that the level of mechanical forces and the type of flow patterns present in the embryo are able to affect gene expression. Here, we highlight the pivotal role for blood flow and physical forces in shaping the cardiovascular system.

Visfatin and cardio-cerebro-vascular disease.

PubMed

Wang, Pei; Vanhoutte, Paul M; Miao, Chao-Yu

2012-01-01

Nicotinamide phosphoribosyltransferase is the rate-limiting enzyme that catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide from nicotinamide. This protein was originally cloned as a putative pre-B cell colony-enhancing factor and also found to be a visceral fat-derived adipokine (visfatin). As a multifunctional protein, visfatin plays an important role in immunity, metabolism, aging, inflammation, and responses to stress. Visfatin also participates in several pathophysiological processes contributing to cardio-cerebro-vascular diseases, including hypertension, atherosclerosis, ischemic heart disease, and ischemic stroke. However, whether visfatin is a friend or a foe in these diseases remains uncertain. This brief review focuses on the current understanding of the complex role of visfatin in the cardio-cerebro-vascular system under normal and pathophysiological conditions.

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.

VA Vascular Injury Study (VAVIS): VA-DoD extremity injury outcomes collaboration.

PubMed

Shireman, Paula K; Rasmussen, Todd E; Jaramillo, Carlos A; Pugh, Mary Jo

2015-02-03

Limb injuries comprise 50-60% of U.S. Service member's casualties of wars in Afghanistan and Iraq. Combat-related vascular injuries are present in 12% of this cohort, a rate 5 times higher than in prior wars. Improvements in medical and surgical trauma care, including initial in-theatre limb salvage approaches (IILS) have resulted in improved survival and fewer amputations, however, the long-term outcomes such as morbidity, functional decline, and risk for late amputation of salvaged limbs using current process of care have not been studied. The long-term care of these injured warfighters poses a significant challenge to the Department of Defense (DoD) and Department of Veterans Affairs (VA). The VA Vascular Injury Study (VAVIS): VA-DoD Extremity Injury Outcomes Collaborative, funded by the VA, Health Services Research and Development Service, is a longitudinal cohort study of Veterans with vascular extremity injuries. Enrollment will begin April, 2015 and continue for 3 years. Individuals with a validated extremity vascular injury in the Department of Defense Trauma Registry will be contacted and will complete a set of validated demographic, social, behavioral, and functional status measures during interview and online/ mailed survey. Primary outcome measures will: 1) Compare injury, demographic and geospatial characteristics of patients with IILS and identify late vascular surgery related limb complications and health care utilization in Veterans receiving VA vs. non-VA care, 2) Characterize the preventive services received by individuals with vascular repair and related outcomes, and 3) Describe patient-reported functional outcomes in Veterans with traumatic vascular limb injuries. This study will provide key information about the current process of care for Active Duty Service members and Veterans with polytrauma/vascular injuries at risk for persistent morbidity and late amputation. The results of this study will be the first step for clinicians in VA and military settings to generate evidence-based treatment and care approaches to these injuries. It will identify areas where rehabilitation medicine and vascular specialty care or telehealth options are needed to allow for better planning, resource utilization, and improved DoD-to-VA care transitions.

20170312 - Adverse Outcome Pathway (AOP) framework for ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Adverse Outcome Pathway (AOP) framework for embryonic ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Automation process for morphometric analysis of volumetric CT data from pulmonary vasculature in rats.

PubMed

Shingrani, Rahul; Krenz, Gary; Molthen, Robert

2010-01-01

With advances in medical imaging scanners, it has become commonplace to generate large multidimensional datasets. These datasets require tools for a rapid, thorough analysis. To address this need, we have developed an automated algorithm for morphometric analysis incorporating A Visualization Workshop computational and image processing libraries for three-dimensional segmentation, vascular tree generation and structural hierarchical ordering with a two-stage numeric optimization procedure for estimating vessel diameters. We combine this new technique with our mathematical models of pulmonary vascular morphology to quantify structural and functional attributes of lung arterial trees. Our physiological studies require repeated measurements of vascular structure to determine differences in vessel biomechanical properties between animal models of pulmonary disease. Automation provides many advantages including significantly improved speed and minimized operator interaction and biasing. The results are validated by comparison with previously published rat pulmonary arterial micro-CT data analysis techniques, in which vessels were manually mapped and measured using intense operator intervention. Published by Elsevier Ireland Ltd.

Vascular Effects of Phytoestrogens and Alternative Menopausal Hormone Therapy in Cardiovascular Disease

PubMed Central

Gencel, Vahide B.; Benjamin, Mina M.; Bahou, Shafik N.; Khalil, Raouf A.

2011-01-01

Phytoestrogens are estrogenic compounds of plant origin classified into different groups including isoflavones, lignans, coumestans and stilbenes. Isoflavones such as genistein and daidzein are the most studied and most potent phytoestrogens, and are found mainly in soy based foods. The effects of phytoestrogens are partly mediated via estrogen receptors (ERs): ERα, ERβ and possibly GPER. The interaction of phytoestrogens with ERs is thought to induce both genomic and non-genomic effects in many tissues including the vasculature. Some phytoestrogens such as genistein have additional non-ER-mediated effects involving signaling pathways such as tyrosine kinase. Experimental studies have shown beneficial effects of phytoestrogens on endothelial cells, vascular smooth muscle, and extracellular matrix. Phytoestrogens may also affect other pathophysiologic vascular processes such as lipid profile, angiogenesis, inflammation, tissue damage by reactive oxygen species, and these effects could delay the progression of atherosclerosis. As recent clinical trials showed no vascular benefits or even increased risk of cardiovascular disease (CVD) and CV events with conventional menopausal hormone therapy (MHT), phytoestrogens are being considered as alternatives to pharmacologic MHT. Epidemiological studies in the Far East population suggest that dietary intake of phytoestrogens may contribute to the decreased incidence of postmenopausal CVD and thromboembolic events. Also, the WHO-CARDIAC study supported that consumption of high soybean diet is associated with lower mortalities from coronary artery disease. However, as with estrogen, there has been some discrepancy between the experimental studies demonstrating the vascular benefits of phytoestrogens and the data from clinical trials. This is likely because the phytoestrogens clinical trials have been limited in many aspects including the number of participants enrolled, the clinical end points investigated, and the lack of long-term follow-up. Further investigation of the cellular mechanisms underlying the vascular effects of phytoestrogens and careful evaluation of the epidemiological evidence and clinical trials of their potential vascular benefits would put forward the use of phytoestrogens as an alternative MHT for the relief of menopausal symptoms and amelioration of postmenopausal CVD. PMID:22070687

Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction.

PubMed

Barton, Matthias; Baretella, Oliver; Meyer, Matthias R

2012-02-01

Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis-related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium-derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, 'premature' vascular aging. Here, we will review some of the pathomechanisms involved in obesity-related activation of endothelium-dependent vasoconstriction, the clinical relevance of obesity-associated vascular risk, and therapeutic interventions using 'endothelial therapy' aiming at maintaining or restoring vascular endothelial health. This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Advanced 3D mesh manipulation in stereolithographic files and post-print processing for the manufacturing of patient-specific vascular flow phantoms

NASA Astrophysics Data System (ADS)

O'Hara, Ryan P.; Chand, Arpita; Vidiyala, Sowmya; Arechavala, Stacie M.; Mitsouras, Dimitrios; Rudin, Stephen; Ionita, Ciprian N.

2016-03-01

Complex vascular anatomies can cause the failure of image-guided endovascular procedures. 3D printed patient-specific vascular phantoms provide clinicians and medical device companies the ability to preemptively plan surgical treatments, test the likelihood of device success, and determine potential operative setbacks. This research aims to present advanced mesh manipulation techniques of stereolithographic (STL) files segmented from medical imaging and post-print surface optimization to match physiological vascular flow resistance. For phantom design, we developed three mesh manipulation techniques. The first method allows outlet 3D mesh manipulations to merge superfluous vessels into a single junction, decreasing the number of flow outlets and making it feasible to include smaller vessels. Next we introduced Boolean operations to eliminate the need to manually merge mesh layers and eliminate errors of mesh self-intersections that previously occurred. Finally we optimize support addition to preserve the patient anatomical geometry. For post-print surface optimization, we investigated various solutions and methods to remove support material and smooth the inner vessel surface. Solutions of chloroform, alcohol and sodium hydroxide were used to process various phantoms and hydraulic resistance was measured and compared with values reported in literature. The newly mesh manipulation methods decrease the phantom design time by 30 - 80% and allow for rapid development of accurate vascular models. We have created 3D printed vascular models with vessel diameters less than 0.5 mm. The methods presented in this work could lead to shorter design time for patient specific phantoms and better physiological simulations.

Advanced 3D Mesh Manipulation in Stereolithographic Files and Post-Print Processing for the Manufacturing of Patient-Specific Vascular Flow Phantoms.

PubMed

O'Hara, Ryan P; Chand, Arpita; Vidiyala, Sowmya; Arechavala, Stacie M; Mitsouras, Dimitrios; Rudin, Stephen; Ionita, Ciprian N

2016-02-27

Complex vascular anatomies can cause the failure of image-guided endovascular procedures. 3D printed patient-specific vascular phantoms provide clinicians and medical device companies the ability to preemptively plan surgical treatments, test the likelihood of device success, and determine potential operative setbacks. This research aims to present advanced mesh manipulation techniques of stereolithographic (STL) files segmented from medical imaging and post-print surface optimization to match physiological vascular flow resistance. For phantom design, we developed three mesh manipulation techniques. The first method allows outlet 3D mesh manipulations to merge superfluous vessels into a single junction, decreasing the number of flow outlets and making it feasible to include smaller vessels. Next we introduced Boolean operations to eliminate the need to manually merge mesh layers and eliminate errors of mesh self-intersections that previously occurred. Finally we optimize support addition to preserve the patient anatomical geometry. For post-print surface optimization, we investigated various solutions and methods to remove support material and smooth the inner vessel surface. Solutions of chloroform, alcohol and sodium hydroxide were used to process various phantoms and hydraulic resistance was measured and compared with values reported in literature. The newly mesh manipulation methods decrease the phantom design time by 30 - 80% and allow for rapid development of accurate vascular models. We have created 3D printed vascular models with vessel diameters less than 0.5 mm. The methods presented in this work could lead to shorter design time for patient specific phantoms and better physiological simulations.

Advanced 3D Mesh Manipulation in Stereolithographic Files and Post-Print Processing for the Manufacturing of Patient-Specific Vascular Flow Phantoms

PubMed Central

O’Hara, Ryan P.; Chand, Arpita; Vidiyala, Sowmya; Arechavala, Stacie M.; Mitsouras, Dimitrios; Rudin, Stephen; Ionita, Ciprian N.

2017-01-01

Complex vascular anatomies can cause the failure of image-guided endovascular procedures. 3D printed patient-specific vascular phantoms provide clinicians and medical device companies the ability to preemptively plan surgical treatments, test the likelihood of device success, and determine potential operative setbacks. This research aims to present advanced mesh manipulation techniques of stereolithographic (STL) files segmented from medical imaging and post-print surface optimization to match physiological vascular flow resistance. For phantom design, we developed three mesh manipulation techniques. The first method allows outlet 3D mesh manipulations to merge superfluous vessels into a single junction, decreasing the number of flow outlets and making it feasible to include smaller vessels. Next we introduced Boolean operations to eliminate the need to manually merge mesh layers and eliminate errors of mesh self-intersections that previously occurred. Finally we optimize support addition to preserve the patient anatomical geometry. For post-print surface optimization, we investigated various solutions and methods to remove support material and smooth the inner vessel surface. Solutions of chloroform, alcohol and sodium hydroxide were used to process various phantoms and hydraulic resistance was measured and compared with values reported in literature. The newly mesh manipulation methods decrease the phantom design time by 30 – 80% and allow for rapid development of accurate vascular models. We have created 3D printed vascular models with vessel diameters less than 0.5 mm. The methods presented in this work could lead to shorter design time for patient specific phantoms and better physiological simulations. PMID:28649165

Netrins and UNC5 receptors in angiogenesis.

PubMed

Freitas, Catarina; Larrivée, Bruno; Eichmann, Anne

2008-01-01

Both neuronal and vascular development require guidance to establish a precise branching pattern of these systems in the vertebrate body. Several molecules implicated in axon navigation have also been shown to regulate vessel sprouting. Among these guidance cues, Netrins constitute a family of diffusible molecules with a bifuncional role in axon pathfinding. Recent findings implicate Netrins in other developmental processes, including vascular development. We here review recent studies and discuss the possible dual function of Netrins and its receptors during branching of blood vessels in developmental and pathological angiogenesis.

The Integrity bare-metal stent made by continuous sinusoid technology.

PubMed

Turco, Mark A

2011-05-01

The Integrity Coronary Stent System (Medtronic Vascular, CA, USA) is a low-profile, open-cell, cobalt-chromium-alloy advanced bare-metal iteration of the well-known Driver/Micro-Driver Coronary Stent System (Medtronic Vascular). The Integrity stent is made with a process called continuous sinusoid technology. This process allows stent construction via wrapping a single thin strand of wire around a mandrel in a sinusoid configuration, with laser fusion of adjacent crowns. The wire-forming process and fusion pattern provide the stent with a continuous preferential bending plane, intended to allow easier access to, and smoother tracking within, distal and tortuous vessels while radial strength is maintained. Continuous sinusoid technology represents innovation in the design of stent platforms and will provide a future stent platform for newer technology, including drug-eluting stent platforms, drug-filled stents and core wire stents.

Melbourne vascular surgical association audit.

PubMed

Beiles, C Barry

2003-01-01

The formation of the Melbourne Vascular Surgical Association has led to the establishment of a vascular surgical audit programme that commenced in January 1999. This has allowed establishment of a benchmark for quality assurance in vascular surgery in Australia. A consultative process allowed widespread adoption of the audit across all public hospital vascular units in Melbourne and the two largest regional centres in Victoria. Data were collected at two points during admission: at operation and at discharge. Risk stratification, using logistic regression and risk-adjusted ratios for adverse events was assessed for comparison of outcomes between units for the first 3 years of data collection. There is regular contact with all participants for data feedback and quality control. The standard of vascular surgery across Victoria is consistent, and there has been excellent compliance by all academic vascular units. Private practice data are less complete, and only half of the vascular surgeons have participated. A statewide audit process is feasible and viable. Coordination by the Melbourne Vascular Surgical Association is crucial for its continued success.

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.

Arabidopsis thickvein mutation affects vein thickness and organ vascularization, and resides in a provascular cell-specific spermine synthase involved in vein definition and in polar auxin transport.

PubMed

Clay, Nicole K; Nelson, Timothy

2005-06-01

Polar auxin transport has been implicated in the induction of vascular tissue and in the definition of vein positions. Leaves treated with chemical inhibitors of polar auxin transport exhibited vascular phenotypes that include increased vein thickness and vascularization. We describe a recessive mutant, thickvein (tkv), which develops thicker veins in leaves and in inflorescence stems. The increased vein thickness is attributable to an increased number of vascular cells. Mutant plants have smaller leaves and shorter inflorescence stems, and this reduction in organ size and height is accompanied by an increase in organ vascularization, which appears to be attributable to an increase in the recruitment of cells into veins. Furthermore, although floral development is normal, auxin transport in the inflorescence stem is significantly reduced in the mutant, suggesting that the defect in auxin transport is responsible for the vascular phenotypes. In the primary root, the veins appear morphologically normal, but root growth in the tkv mutant is hypersensitive to exogenous cytokinin. The tkv mutation was found to reside in the ACL5 gene, which encodes a spermine synthase and whose expression is specific to provascular cells. We propose that ACL5/TKV is involved in vein definition (defining the boundaries between veins and nonvein regions) and in polar auxin transport, and that polyamines are involved in this process.

Arabidopsis thickvein Mutation Affects Vein Thickness and Organ Vascularization, and Resides in a Provascular Cell-Specific Spermine Synthase Involved in Vein Definition and in Polar Auxin Transport1

PubMed Central

Clay, Nicole K.; Nelson, Timothy

2005-01-01

Polar auxin transport has been implicated in the induction of vascular tissue and in the definition of vein positions. Leaves treated with chemical inhibitors of polar auxin transport exhibited vascular phenotypes that include increased vein thickness and vascularization. We describe a recessive mutant, thickvein (tkv), which develops thicker veins in leaves and in inflorescence stems. The increased vein thickness is attributable to an increased number of vascular cells. Mutant plants have smaller leaves and shorter inflorescence stems, and this reduction in organ size and height is accompanied by an increase in organ vascularization, which appears to be attributable to an increase in the recruitment of cells into veins. Furthermore, although floral development is normal, auxin transport in the inflorescence stem is significantly reduced in the mutant, suggesting that the defect in auxin transport is responsible for the vascular phenotypes. In the primary root, the veins appear morphologically normal, but root growth in the tkv mutant is hypersensitive to exogenous cytokinin. The tkv mutation was found to reside in the ACL5 gene, which encodes a spermine synthase and whose expression is specific to provascular cells. We propose that ACL5/TKV is involved in vein definition (defining the boundaries between veins and nonvein regions) and in polar auxin transport, and that polyamines are involved in this process. PMID:15894745

Spanish Clinical Guidelines on Vascular Access for Haemodialysis.

PubMed

Ibeas, José; Roca-Tey, Ramon; Vallespín, Joaquín; Moreno, Teresa; Moñux, Guillermo; Martí-Monrós, Anna; Del Pozo, José Luis; Gruss, Enrique; Ramírez de Arellano, Manel; Fontseré, Néstor; Arenas, María Dolores; Merino, José Luis; García-Revillo, José; Caro, Pilar; López-Espada, Cristina; Giménez-Gaibar, Antonio; Fernández-Lucas, Milagros; Valdés, Pablo; Fernández-Quesada, Fidel; de la Fuente, Natalia; Hernán, David; Arribas, Patricia; Sánchez de la Nieta, María Dolores; Martínez, María Teresa; Barba, Ángel

2017-11-01

Vascular access for haemodialysis is key in renal patients both due to its associated morbidity and mortality and due to its impact on quality of life. The process, from the creation and maintenance of vascular access to the treatment of its complications, represents a challenge when it comes to decision-making, due to the complexity of the existing disease and the diversity of the specialities involved. With a view to finding a common approach, the Spanish Multidisciplinary Group on Vascular Access (GEMAV), which includes experts from the five scientific societies involved (nephrology [S.E.N.], vascular surgery [SEACV], vascular and interventional radiology [SERAM-SERVEI], infectious diseases [SEIMC] and nephrology nursing [SEDEN]), along with the methodological support of the Cochrane Center, has updated the Guidelines on Vascular Access for Haemodialysis, published in 2005. These guidelines maintain a similar structure, in that they review the evidence without compromising the educational aspects. However, on one hand, they provide an update to methodology development following the guidelines of the GRADE system in order to translate this systematic review of evidence into recommendations that facilitate decision-making in routine clinical practice, and, on the other hand, the guidelines establish quality indicators which make it possible to monitor the quality of healthcare. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Vascular Endothelial Growth Factor–Mediated Islet Hypervascularization and Inflammation Contribute to Progressive Reduction of β-Cell Mass

PubMed Central

Agudo, Judith; Ayuso, Eduard; Jimenez, Veronica; Casellas, Alba; Mallol, Cristina; Salavert, Ariana; Tafuro, Sabrina; Obach, Mercè; Ruzo, Albert; Moya, Marta; Pujol, Anna; Bosch, Fatima

2012-01-01

Type 2 diabetes (T2D) results from insulin resistance and inadequate insulin secretion. Insulin resistance initially causes compensatory islet hyperplasia that progresses to islet disorganization and altered vascularization, inflammation, and, finally, decreased functional β-cell mass and hyperglycemia. The precise mechanism(s) underlying β-cell failure remain to be elucidated. In this study, we show that in insulin-resistant high-fat diet-fed mice, the enhanced islet vascularization and inflammation was parallel to an increased expression of vascular endothelial growth factor A (VEGF). To elucidate the role of VEGF in these processes, we have genetically engineered β-cells to overexpress VEGF (in transgenic mice or after adeno-associated viral vector-mediated gene transfer). We found that sustained increases in β-cell VEGF levels led to disorganized, hypervascularized, and fibrotic islets, progressive macrophage infiltration, and proinflammatory cytokine production, including tumor necrosis factor-α and interleukin-1β. This resulted in impaired insulin secretion, decreased β-cell mass, and hyperglycemia with age. These results indicate that sustained VEGF upregulation may participate in the initiation of a process leading to β-cell failure and further suggest that compensatory islet hyperplasia and hypervascularization may contribute to progressive inflammation and β-cell mass loss during T2D. PMID:22961079

Molecular basis for endothelial lumen formation and tubulogenesis during vasculogenesis and angiogenic sprouting

PubMed Central

Davis, George E.; Stratman, Amber N.; Sacharidou, Anastasia; Koh, Wonshill

2013-01-01

Many studies reveal a fundamental role for extracellular matrix-mediated signaling through integrins and Rho GTPases as well as matrix metalloproteinases (MMPs) in the molecular control of vascular tube morphogenesis in three-dimensional (3D) tissue environments. Recent work has defined an EC lumen signaling complex of proteins that controls these vascular morphogenic events. These findings reveal a signaling interdependence between Cdc42 and MT1-MMP to control the 3D matrix-specific process of EC tubulogenesis. The EC tube formation process results in the creation of a network of proteolytically-generated vascular guidance tunnels in 3D matrices that are utilized to remodel EC-lined tubes through EC motility and could facilitate processes such as flow-induced remodeling and arteriovenous EC sorting and differentiation. Within vascular guidance tunnels, key dynamic interactions occur between endothelial cells (ECs) and pericytes to affect vessel remodeling, diameter, and vascular basement membrane matrix assembly, a fundamental process necessary for endothelial tube maturation and stabilization. Thus, the EC lumen and tube formation mechanism coordinates the concomitant establishment of a network of vascular tubes within tunnel spaces to allow for flow responsiveness, EC-mural cell interactions, and vascular extracellular matrix assembly to control the development of the functional microcirculation. PMID:21482411

Inflammation and vascular remodeling in the ventral hippocampus contributes to vulnerability to stress.

PubMed

Pearson-Leary, J; Eacret, D; Chen, R; Takano, H; Nicholas, B; Bhatnagar, S

2017-06-27

During exposure to chronic stress, some individuals engage in active coping behaviors that promote resiliency to stress. Other individuals engage in passive coping that is associated with vulnerability to stress and with anxiety and depression. In an effort to identify novel molecular mechanisms that underlie vulnerability or resilience to stress, we used nonbiased analyses of microRNAs in the ventral hippocampus (vHPC) to identify those miRNAs differentially expressed in active (long-latency (LL)/resilient) or passive (short-latency (SL)/vulnerable) rats following chronic social defeat. In the vHPC of active coping rats, miR-455-3p level was increased, while miR-30e-3p level was increased in the vHPC of passive coping rats. Pathway analyses identified inflammatory and vascular remodeling pathways as enriched by genes targeted by these microRNAs. Utilizing several independent markers for blood vessels, inflammatory processes and neural activity in the vHPC, we found that SL/vulnerable rats exhibit increased neural activity, vascular remodeling and inflammatory processes that include both increased blood-brain barrier permeability and increased number of microglia in the vHPC relative to control and resilient rats. To test the relevance of these changes for the development of the vulnerable phenotype, we used pharmacological approaches to determine the contribution of inflammatory processes in mediating vulnerability and resiliency. Administration of the pro-inflammatory cytokine vascular endothelial growth factor-164 increased vulnerability to stress, while the non-steroidal anti-inflammatory drug meloxicam attenuated vulnerability. Collectively, these results show that vulnerability to stress is determined by a re-designed neurovascular unit characterized by increased neural activity, vascular remodeling and pro-inflammatory mechanisms in the vHPC. These results suggest that dampening inflammatory processes by administering anti-inflammatory agents reduces vulnerability to stress. These results have translational relevance as they suggest that administration of anti-inflammatory agents may reduce the impact of stress or trauma in vulnerable individuals.

Inflammation and vascular remodeling in the ventral hippocampus contributes to vulnerability to stress

PubMed Central

Pearson-Leary, J; Eacret, D; Chen, R; Takano, H; Nicholas, B; Bhatnagar, S

2017-01-01

During exposure to chronic stress, some individuals engage in active coping behaviors that promote resiliency to stress. Other individuals engage in passive coping that is associated with vulnerability to stress and with anxiety and depression. In an effort to identify novel molecular mechanisms that underlie vulnerability or resilience to stress, we used nonbiased analyses of microRNAs in the ventral hippocampus (vHPC) to identify those miRNAs differentially expressed in active (long-latency (LL)/resilient) or passive (short-latency (SL)/vulnerable) rats following chronic social defeat. In the vHPC of active coping rats, miR-455-3p level was increased, while miR-30e-3p level was increased in the vHPC of passive coping rats. Pathway analyses identified inflammatory and vascular remodeling pathways as enriched by genes targeted by these microRNAs. Utilizing several independent markers for blood vessels, inflammatory processes and neural activity in the vHPC, we found that SL/vulnerable rats exhibit increased neural activity, vascular remodeling and inflammatory processes that include both increased blood–brain barrier permeability and increased number of microglia in the vHPC relative to control and resilient rats. To test the relevance of these changes for the development of the vulnerable phenotype, we used pharmacological approaches to determine the contribution of inflammatory processes in mediating vulnerability and resiliency. Administration of the pro-inflammatory cytokine vascular endothelial growth factor-164 increased vulnerability to stress, while the non-steroidal anti-inflammatory drug meloxicam attenuated vulnerability. Collectively, these results show that vulnerability to stress is determined by a re-designed neurovascular unit characterized by increased neural activity, vascular remodeling and pro-inflammatory mechanisms in the vHPC. These results suggest that dampening inflammatory processes by administering anti-inflammatory agents reduces vulnerability to stress. These results have translational relevance as they suggest that administration of anti-inflammatory agents may reduce the impact of stress or trauma in vulnerable individuals. PMID:28654094

Vascular signaling abnormalities in Alzheimer disease.

PubMed

Grammas, Paula; Sanchez, Alma; Tripathy, Debjani; Luo, Ester; Martinez, Joseph

2011-08-01

Our laboratory has documented that brain microvessels derived from patients with Alzheimer disease (AD) express or release a myriad of factors that have been implicated in vascular activation and angiogenesis. In addition, we have documented that signaling cascades associated with vascular activation and angiogenesis are upregulated in AD-derived brain microvessels. These results are consistent with emerging data suggesting that factors and processes characteristic of vascular activation and angiogenesis are found in the AD brain. Despite increases in proangiogenic factors and signals in the AD brain, however, evidence for increased vascularity in AD is lacking. Cerebral hypoperfusion/hypoxia, a potent stimulus for vascular activation and angiogenesis, triggers hypometabolic, cognitive, and degenerative changes in the brain. In our working model, hypoxia stimulates the angiogenic process; yet, there is no new vessel growth. Therefore, there are no feedback signals to shut off vascular activation, and endothelial cells become irreversibly activated. This activation results in release of a large number of proteases, inflammatory proteins, and other gene products with biologic activity that can injure or kill neurons. Pathologic activation of brain vasculature may contribute noxious mediators that lead to neuronal injury and disease processes in AD brains. This concept is supported by preliminary experiments in our laboratory, which show that pharmacologic blockade of vascular activation improves cognitive function in an animal model of AD. Thus, "vascular activation" could be a novel, unexplored therapeutic target in AD.

Application of vascular aquatic plants for pollution removal, energy and food production in a biological system

NASA Technical Reports Server (NTRS)

Wolverton, B. C.; Barlow, R. M.; Mcdonald, R. C.

1975-01-01

Vascular aquatic plants such as water hyacinths (Eichhornia crassipes) (Mart.) Solms and alligator weeds (Alternanthera philoxeroides) (Mart.) Griesb., when utilized in a controlled biological system (including a regular program of harvesting to achieve maximum growth and pollution removal efficiency), may represent a remarkably efficient and inexpensive filtration and disposal system for toxic materials and sewage released into waters near urban and industrial areas. The harvested and processed plant materials are sources of energy, fertilizer, animal feed, and human food. Such a system has industrial, municipal, and agricultural applications.

Application of vascular aquatic plants for pollution removal, energy, and food production in a biological system

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

Wolverton, B.C.; Barlow, R.M.; Mcdonald, R.C.

1975-05-12

Vascular aquatic plants such as water hyacinths (Eichhornia crassipes) (Mart.) Solms and alligator weeds (Alternanthera philoxeroides) (Mart.) Griesb., when utilized in a controlled biological system (including a regular program of harvesting to achieve maximum growth and pollution removal efficiency), may represent a remarkably efficient and inexpensive filtration and disposal system for toxic materials and sewage released into waters near urban and industrial areas. The harvested and processed plant materials are sources of energy, fertilizer, animal feed, and human food. Such a system has industrial, municipal, and agricultural applications. (Author) (GRA)

[Morphological pathology of vessels in granulomatosis with polyangiitis (Wegener's disease)].

PubMed

Zerbino, D D; Zimba, E A

2015-01-01

to investigate the incidence of injuries in different vascular beds and the morphopathological changes in vessels in granulomatosis with polyangiitis. The morphopathological features of vascular injuries were investigated in 11 dead patients aged 16--74 years with granulomatosis with polyangiitis. Proliferative and destructive angiitis with predominant involvement of microcirculatory vessels and with development of necrosis-prone granulomas in their walls and perivascularly was established to underlie the clinical manifestations of granulomatosis with polyangiitis. The most typical localization of the pathologic process is the vessels of the upper respiratory tract, lungs, and kidneys. Cardiopulmonary and renal failures are causes of death in the majority of cases. It should be noted that the vessels of the heart, liver, and gastrointestinal tract are frequently involved in the pathological process. Vascular changes in these organs determine the clinical features of granulomatosis with polyangiitis and lead to a number of fatal complications. Granulomatosis with polyangiitis is a systemic disease with polymorphism of clinical manifestations, which requires in-depth analysis based on current precision patient examination methods, including a histopathological study.

The multiple roles of EG-VEGF/PROK1 in normal and pathological placental angiogenesis.

PubMed

Alfaidy, Nadia; Hoffmann, Pascale; Boufettal, Houssine; Samouh, Naima; Aboussaouira, Touria; Benharouga, Mohamed; Feige, Jean-Jacques; Brouillet, Sophie

2014-01-01

Placentation is associated with several steps of vascular adaptations throughout pregnancy. These vascular changes occur both on the maternal and fetal sides, consisting of maternal uterine spiral arteries remodeling and placental vasculogenesis and angiogenesis, respectively. Placental angiogenesis is a pivotal process for efficient fetomaternal exchanges and placental development. This process is finely controlled throughout pregnancy, and it involves ubiquitous and pregnancy-specific angiogenic factors. In the last decade, endocrine gland derived vascular endothelial growth factor (EG-VEGF), also called prokineticin 1 (PROK1), has emerged as specific placental angiogenic factor that controls many aspects of normal and pathological placental angiogenesis such as recurrent pregnancy loss (RPL), gestational trophoblastic diseases (GTD), fetal growth restriction (FGR), and preeclampsia (PE). This review recapitulates EG-VEGF mediated-angiogenesis within the placenta and at the fetomaternal interface and proposes that its deregulation might contribute to the pathogenesis of several placental diseases including FGR and PE. More importantly this paper argues for EG-VEGF clinical relevance as a potential biomarker of the onset of pregnancy pathologies and discusses its potential usefulness for future therapeutic directions.

Postischemic revascularization: from cellular and molecular mechanisms to clinical applications.

PubMed

Silvestre, Jean-Sébastien; Smadja, David M; Lévy, Bernard I

2013-10-01

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

The regulation of Jmjd3 upon the expression of NF-κB downstream inflammatory genes in LPS activated vascular endothelial cells

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

Yu, Shaoqing; Graduate School of Medicine, Nanchang University, Nanchang; Chen, Xia

Inflammatory mediators and adhesion molecules have been implicated in a variety of diseases including atherosclerosis. As both the mediator-releasing and targeted cells, vascular endothelial cells play key role in pathological processes. NF-κB signaling regulates a cluster of inflammatory factors in LPS-activated vascular endothelial cells but the underlying mechanisms remain largely unknown. Here, we investigated the epigenetic regulation of LPS upon the expression of inflammatory mediators and adhesion molecules. We found that LPS treatment promoted jmjd3 expression, enhanced Jmjd3 nuclear accumulation in human vascular endothelial cells. In addition, LPS enhanced the demethylation of H3K27me3, a specific substrate of Jmjd3. LPS treatmentmore » recruited Jmjd3 and NF-κB to the promoter region of target genes, suggesting Jmjd3 synergizes with NF-κB to activate the expression of target genes. We further found that Jmjd3 attenuated the methylation status in promoter region of target genes, culminating in target gene expression. Our findings unveil epigenetic regulations of LPS upon NF-κB pathway and identify Jmjd3 as a critical modulator of NF-κB pathway and potential therapeutic target for NF-κB related diseases including atherosclerosis.« less

The Interaction Between IGF-1, Atherosclerosis and Vascular Aging

PubMed Central

Higashi, Yusuke; Quevedo, Henry C.; Tiwari, Summit; Sukhanov, Sergiy; Shai, Shaw-Yung; Anwar, Asif; Delafontaine, Patrice

2014-01-01

The process of vascular aging encompasses alterations in the function of endothelial (EC) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species (ROS) generation and inflammatory signaling, increased migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein-B containing low density lipoproteins resulting in activation of endothelial cells and recruitment of monocytes. Activated endothelial cells secrete “chemokines” that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a pro-inflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and non-vascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 (IGF-1) exerts anti-oxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability. PMID:24943302

The Tissue-Engineered Vascular Graft—Past, Present, and Future

PubMed Central

Pashneh-Tala, Samand; MacNeil, Sheila

2016-01-01

Cardiovascular disease is the leading cause of death worldwide, with this trend predicted to continue for the foreseeable future. Common disorders are associated with the stenosis or occlusion of blood vessels. The preferred treatment for the long-term revascularization of occluded vessels is surgery utilizing vascular grafts, such as coronary artery bypass grafting and peripheral artery bypass grafting. Currently, autologous vessels such as the saphenous vein and internal thoracic artery represent the gold standard grafts for small-diameter vessels (<6 mm), outperforming synthetic alternatives. However, these vessels are of limited availability, require invasive harvest, and are often unsuitable for use. To address this, the development of a tissue-engineered vascular graft (TEVG) has been rigorously pursued. This article reviews the current state of the art of TEVGs. The various approaches being explored to generate TEVGs are described, including scaffold-based methods (using synthetic and natural polymers), the use of decellularized natural matrices, and tissue self-assembly processes, with the results of various in vivo studies, including clinical trials, highlighted. A discussion of the key areas for further investigation, including graft cell source, mechanical properties, hemodynamics, integration, and assessment in animal models, is then presented. PMID:26447530

Expression and Function of Anti-Inflammatory Interleukins: The Other Side of the Vascular Response to Injury

PubMed Central

Cuneo, Anthony A.; Autieri, Michael V.

2012-01-01

Common to multiple vascular diseases, including atherosclerosis, interventional restenosis, and transplant vasculopathy, is a localized inflammatory reaction. Activated vascular smooth muscle cells (VSMC) respond to local inflammation and migrate from the media into the lumen of the vessel where they proliferate and synthesize cytokines which they respond to in an autocrine fashion, sustaining the progression of the lesion. The deleterious effects of pro-inflammatory cytokines, particularly immunomodulatory interleukins, on vascular pathophysiology and development of these maladaptive processes have been the subject of intense study. Although a great deal of attention has been given to the negative effects of pro-inflammatory cytokines and interleukins, relatively little has been reported on the potentially beneficial paracrine and autocrine effects of anti-inflammatory interleukins on the vascular response to injury. The vast majority of emphasis on secretion and function of anti-inflammatory mediators has been placed on leukocytes. Consequently, the role of non-immune cells, and direct effects of anti-inflammatory interleukins on vascular cells is poorly understood. We will review the molecular mechanisms whereby anti-inflammatory interleukins inhibit signal transduction and gene expression in inflammatory cells. We will review studies in which beneficial “indirect” effects of anti-inflammatory interleukins on progression of vascular disease are achieved by modulation of immune function. We will also present the limited studies in which “direct” effects of these interleukins on VSMC and endothelial cells dampen the vascular response to injury. We propose that expression of immunomodulatory cytokines by activated vasculature may represent an auto-regulatory feed back mechanism to promote resolution of the vascular response to injury. PMID:19601851

Stroke injury, cognitive impairment and vascular dementia☆

PubMed Central

Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi

2016-01-01

The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700

Gap-free segmentation of vascular networks with automatic image processing pipeline.

PubMed

Hsu, Chih-Yang; Ghaffari, Mahsa; Alaraj, Ali; Flannery, Michael; Zhou, Xiaohong Joe; Linninger, Andreas

2017-03-01

Current image processing techniques capture large vessels reliably but often fail to preserve connectivity in bifurcations and small vessels. Imaging artifacts and noise can create gaps and discontinuity of intensity that hinders segmentation of vascular trees. However, topological analysis of vascular trees require proper connectivity without gaps, loops or dangling segments. Proper tree connectivity is also important for high quality rendering of surface meshes for scientific visualization or 3D printing. We present a fully automated vessel enhancement pipeline with automated parameter settings for vessel enhancement of tree-like structures from customary imaging sources, including 3D rotational angiography, magnetic resonance angiography, magnetic resonance venography, and computed tomography angiography. The output of the filter pipeline is a vessel-enhanced image which is ideal for generating anatomical consistent network representations of the cerebral angioarchitecture for further topological or statistical analysis. The filter pipeline combined with computational modeling can potentially improve computer-aided diagnosis of cerebrovascular diseases by delivering biometrics and anatomy of the vasculature. It may serve as the first step in fully automatic epidemiological analysis of large clinical datasets. The automatic analysis would enable rigorous statistical comparison of biometrics in subject-specific vascular trees. The robust and accurate image segmentation using a validated filter pipeline would also eliminate operator dependency that has been observed in manual segmentation. Moreover, manual segmentation is time prohibitive given that vascular trees have more than thousands of segments and bifurcations so that interactive segmentation consumes excessive human resources. Subject-specific trees are a first step toward patient-specific hemodynamic simulations for assessing treatment outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Creating Perfused Functional Vascular Channels Using 3D Bio-Printing Technology

PubMed Central

Lee, Vivian K.; Kim, Diana Y.; Ngo, Haygan; Lee, Young; Seo, Lan; Yoo, Seung-Schik; Vincent, Peter A.; Dai, Guohao

2014-01-01

We developed a methodology using 3D bio-printing technology to create a functional in vitro vascular channel with perfused open lumen using only cells and biological matrices. The fabricated vasculature has a tight, confluent endothelium lining, presenting barrier function for both plasma protein and high-molecular weight dextran molecule. The fluidic vascular channel is capable of supporting the viability of tissue up to 5mm in distance at 5 million cells/mL density under the physiological flow condition. In static-cultured vascular channels, active angiogenic sprouting from the vessel surface was observed whereas physiological flow strongly suppressed this process. Gene expression analysis were reported in this study to show the potential of this vessel model in vascular biology research. The methods have great potential in vascularized tissue fabrication using 3D bio-printing technology as the vascular channel is simultaneously created while cells and matrix are printed around the channel in desired 3D patterns. It can also serve as a unique experimental tool for investigating fundamental mechanisms of vascular remodeling with extracellular matrix and maturation process under 3D flow condition. PMID:24965886

Vascular endothelial growth factor signaling regulates the segregation of artery and vein via ERK activity during vascular development

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

Kim, Se-Hee; Schmitt, Christopher E.; Woolls, Melissa J.

Highlights: ► VEGF-A signaling regulates the segregation of axial vessels. ► VEGF-A signaling is mediated by PKC and ERK in this process. ► Ectopic activation of ERK is sufficient to rescue defects in vessel segregation. -- Abstract: Segregation of two axial vessels, the dorsal aorta and caudal vein, is one of the earliest patterning events occur during development of vasculature. Despite the importance of this process and recent advances in our understanding on vascular patterning during development, molecular mechanisms that coordinate the segregation of axial vessels remain largely elusive. In this report, we find that vascular endothelial growth factor-A (Vegf-A)more » signaling regulates the segregation of dorsal aorta and axial vein during development. Inhibition of Vegf-A pathway components including ligand Vegf-A and its cognate receptor Kdrl, caused failure in segregation of axial vessels in zebrafish embryos. Similarly, chemical inhibition of Mitogen-activated protein kinase kinase (Map2k1)/Extracellular-signal-regulated kinases (Erk) and phosphatidylinositol 3-kinases (PI3 K), which are downstream effectors of Vegf-A signaling pathway, led to the fusion of two axial vessels. Moreover, we find that restoring Erk activity by over-expression of constitutively active MEK in embryos with a reduced level of Vegf-A signaling can rescue the defects in axial vessel segregation. Taken together, our data show that segregation of axial vessels requires the function of Vegf-A signaling, and Erk may function as the major downstream effector in this process.« less

Rapid engineering of endothelial cell-lined vascular-like structures in in situ crosslinkable hydrogels.

PubMed

Kageyama, Tatsuto; Kakegawa, Takahiro; Osaki, Tatsuya; Enomoto, Junko; Ito, Taichi; Nittami, Tadashi; Fukuda, Junji

2014-06-01

Fabrication of perfusable vascular networks in vitro is one of the most critical challenges in the advancement of tissue engineering. Because cells consume oxygen and nutrients during the fabrication process, a rapid fabrication approach is necessary to construct cell-dense vital tissues and organs, such as the liver. In this study, we propose a rapid molding process using an in situ crosslinkable hydrogel and electrochemical cell transfer for the fabrication of perfusable vascular structures. The in situ crosslinkable hydrogel was composed of hydrazide-modified gelatin (gelatin-ADH) and aldehyde-modified hyaluronic acid (HA-CHO). By simply mixing these two solutions, the gelation occurred in less than 20 s through the formation of a stable hydrazone bond. To rapidly transfer cells from a culture surface to the hydrogel, we utilized a zwitterionic oligopeptide, which forms a self-assembled molecular layer on a gold surface. Human umbilical vein endothelial cells adhering on a gold surface via the oligopeptide layer were transferred to the hydrogel within 5 min, along with electrochemical desorption of the oligopeptides. This approach was applicable to cylindrical needles 200-700 µm in diameter, resulting in the formation of perfusable microchannels where the internal surface was fully enveloped with the transferred endothelial cells. The entire fabrication process was completed within 10 min, including 20 s for the hydrogel crosslinking and 5 min for the electrochemical cell transfer. This rapid fabrication approach may provide a promising strategy to construct perfusable vasculatures in cell-dense tissue constructs and subsequently allow cells to organize complicated and fully vascularized tissues while preventing hypoxic cell injury.

Signaling pathways effecting crosstalk between cartilage and adjacent tissues: Seminars in cell and developmental biology: The biology and pathology of cartilage.

PubMed

Maes, Christa

2017-02-01

Endochondral ossification, the mechanism responsible for the development of the long bones, is dependent on an extremely stringent coordination between the processes of chondrocyte maturation in the growth plate, vascular expansion in the surrounding tissues, and osteoblast differentiation and osteogenesis in the perichondrium and the developing bone center. The synchronization of these processes occurring in adjacent tissues is regulated through vigorous crosstalk between chondrocytes, endothelial cells and osteoblast lineage cells. Our knowledge about the molecular constituents of these bidirectional communications is undoubtedly incomplete, but certainly some signaling pathways effective in cartilage have been recognized to play key roles in steering vascularization and osteogenesis in the perichondrial tissues. These include hypoxia-driven signaling pathways, governed by the hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF), which are absolutely essential for the survival and functioning of chondrocytes in the avascular growth plate, at least in part by regulating the oxygenation of developing cartilage through the stimulation of angiogenesis in the surrounding tissues. A second coordinating signal emanating from cartilage and regulating developmental processes in the adjacent perichondrium is Indian Hedgehog (IHH). IHH, produced by pre-hypertrophic and early hypertrophic chondrocytes in the growth plate, induces the differentiation of adjacent perichondrial progenitor cells into osteoblasts, thereby harmonizing the site and time of bone formation with the developmental progression of chondrogenesis. Both signaling pathways represent vital mediators of the tightly organized conversion of avascular cartilage into vascularized and mineralized bone during endochondral ossification. Copyright © 2016. Published by Elsevier Ltd.

Possible role of mechanical force in regulating regeneration of the vascularized fat flap inside a tissue engineering chamber.

PubMed

Ye, Yuan; Yuan, Yi; Lu, Feng; Gao, Jianhua

2015-12-01

In plastic and reconstructive surgery, adipose tissue is widely used as effective filler for tissue defects. Strategies for treating soft tissue deficiency, which include free adipose tissue grafts, use of hyaluronic acid, collagen injections, and implantation of synthetic materials, have several clinical limitations. With the aim of overcoming these limitations, researchers have recently utilized tissue engineering chambers to produce large volumes of engineered vascularized fat tissue. However, the process of growing fat tissue in a chamber is still relatively limited, and can result in unpredictable or dissatisfactory final tissue volumes. Therefore, detailed understanding of the process is both necessary and urgent. Many studies have shown that mechanical force can change the function of cells via mechanotransduction. Here, we hypothesized that, besides the inflammatory response, one of the key factors to control the regeneration of vascularized fat flap inside a tissue engineering chamber might be the balance of mechanical forces. To test our hypothesis, we intend to change the balance of forces by means of measures in order to make the equilibrium point in favor of the direction of regeneration. If those measures proved to be feasible, they could be applied in clinical practice to engineer vascularized adipose tissue of predictable size and shape, which would in turn help in the advancement of tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulatory mechanisms for specification and patterning of plant vascular tissues.

PubMed

Caño-Delgado, Ana; Lee, Ji-Young; Demura, Taku

2010-01-01

Plant vascular tissues, the conduits of water, nutrients, and small molecules, play important roles in plant growth and development. Vascular tissues have allowed plants to successfully adapt to various environmental conditions since they evolved 450 Mya. The majority of plant biomass, an important source of renewable energy, comes from the xylem of the vascular tissues. Efforts have been made to identify the underlying mechanisms of cell specification and patterning of plant vascular tissues and their proliferation. The formation of the plant vascular system is a complex process that integrates signaling and gene regulation at transcriptional and posttranscriptional levels. Recently, a wealth of molecular genetic studies and the advent of cell biology and genomic tools have enabled important progress toward understanding its underlying mechanisms. Here, we provide a comprehensive review of the cell and developmental processes of plant vascular tissue and resources recently available for studying them that will enable the discovery of new ways to develop sustainable energy using plant biomass.

Nanotechnology in vascular tissue engineering: from nanoscaffolding towards rapid vessel biofabrication.

PubMed

Mironov, Vladimir; Kasyanov, Vladimir; Markwald, Roger R

2008-06-01

The existing methods of biofabrication for vascular tissue engineering are still bioreactor-based, extremely expensive, laborious and time consuming and, furthermore, not automated, which would be essential for an economically successful large-scale commercialization. The advances in nanotechnology can bring additional functionality to vascular scaffolds, optimize internal vascular graft surface and even help to direct the differentiation of stem cells into the vascular cell phenotype. The development of rapid nanotechnology-based methods of vascular tissue biofabrication represents one of most important recent technological breakthroughs in vascular tissue engineering because it dramatically accelerates vascular tissue assembly and, importantly, also eliminates the need for a bioreactor-based scaffold cellularization process.

Ex vivo method to visualize and quantify vascular networks in native and tissue engineered skin.

PubMed

Egaña, José Tomás; Condurache, Alexandru; Lohmeyer, Jörn Andreas; Kremer, Mathias; Stöckelhuber, Beate M; Lavandero, Sergio; Machens, Hans-Günther

2009-03-01

Neovascularization plays a pivotal role in tissue engineering and tissue regeneration. However, reliable technologies to visualize and quantify blood vessel networks in target tissue areas are still pending. In this work, we introduce a new method which allows comparing vascularization levels in normal and tissue-engineered skin. Normal skin was isolated, and vascular dermal regeneration was analyzed based on tissue transillumination and computerized digital segmentation. For tissue-engineered skin, a bilateral full skin defect was created in a nude mouse model and then covered with a commercially available scaffold for dermal regeneration. After 3 weeks, the whole skin (including scaffold for dermal regeneration) was harvested, and vascularization levels were analyzed. The blood vessel network in the skin was better visualized by transillumination than by radio-angiographic studies, the gold standard for angiographies. After visualization, the whole vascular network was digitally segmented showing an excellent overlapping with the original pictures. Quantification over the digitally segmented picture was performed, and an index of vascularization area (VAI) and length (VLI) of the vessel network was obtained in target tissues. VAI/VLI ratio was calculated to obtain the vessel size index. We present a new technique which has several advantages compared to others, as animals do not require intravascular perfusions, total areas of interest can be quantitatively analyzed at once, and the same target tissue can be processed for further experimental analysis.

Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review

PubMed Central

D'hondt, Sanne; Van Damme, Tim; Malfait, Fransiska

2018-01-01

Purpose Within the spectrum of the Ehlers-Danlos syndromes (EDS), vascular complications are usually associated with the vascular subtype of EDS. Vascular complications are also observed in other EDS subtypes, but the reports are anecdotal and the information is dispersed. To better document the nature of vascular complications among “nonvascular” EDS subtypes, we performed a systematic review. Methods We queried three databases for English-language studies from inception until May 2017, documenting both phenotypes and genotypes of patients with nonvascular EDS subtypes. The outcome included the number and nature of vascular complications. Results A total of 112 papers were included and data were collected from 467 patients, of whom 77 presented with a vascular phenotype. Severe complications included mainly hematomas (53%), frequently reported in musculocontractural and classical-like EDS; intracranial hemorrhages (18%), with a high risk in dermatosparaxis EDS; and arterial dissections (16%), frequently reported in kyphoscoliotic and classical EDS. Other, more minor, vascular complications were reported in cardiac-valvular, arthrochalasia, spondylodysplastic, and periodontal EDS. Conclusion Potentially life-threatening vascular complications are a rare but important finding in several nonvascular EDS subtypes, highlighting a need for more systematic documentation. This review will help familiarize clinicians with the spectrum of vascular complications in EDS and guide follow-up and management. PMID:28981071

Blood Vessels in Allotransplantation.

PubMed

Abrahimi, P; Liu, R; Pober, J S

2015-07-01

Human vascularized allografts are perfused through blood vessels composed of cells (endothelium, pericytes, and smooth muscle cells) that remain largely of graft origin and are thus subject to host alloimmune responses. Graft vessels must be healthy to maintain homeostatic functions including control of perfusion, maintenance of permselectivity, prevention of thrombosis, and participation in immune surveillance. Vascular cell injury can cause dysfunction that interferes with these processes. Graft vascular cells can be activated by mediators of innate and adaptive immunity to participate in graft inflammation contributing to both ischemia/reperfusion injury and allograft rejection. Different forms of rejection may affect graft vessels in different ways, ranging from thrombosis and neutrophilic inflammation in hyperacute rejection, to endothelialitis/intimal arteritis and fibrinoid necrosis in acute cell-mediated or antibody-mediated rejection, respectively, and to diffuse luminal stenosis in chronic rejection. While some current therapies targeting the host immune system do affect graft vascular cells, direct targeting of the graft vasculature may create new opportunities for preventing allograft injury and loss. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Insulin resistance, metabolic stress, and atherosclerosis

PubMed Central

Pansuria, Meghana; Xi, Hang; Li, Le; Yang, Xiao-Feng; Wang, Hong

2012-01-01

Atherosclerosis, a pathological process that underlies the development of cardiovascular disease, is the primary cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). T2DM is characterized by hyperglycemia and insulin resistance (IR), in which target tissues fail to respond to insulin. Systemic IR is associated with impaired insulin signaling in the metabolic tissues and vasculature. Insulin receptor is highly expressed in the liver, muscle, pancreas, and adipose tissue. It is also expressed in vascular cells. It has been suggested that insulin signaling in vascular cells regulates cell proliferation and vascular function. In this review, we discuss the association between IR, metabolic stress, and atherosclerosis with focus on 1) tissue and cell distribution of insulin receptor and its differential signaling transduction and 2) potential mechanism of insulin signaling impairment and its role in the development of atherosclerosis and vascular function in metabolic disorders including hyperglycemia, hypertension, dyslipidemia, and hyperhomocysteinemia. We propose that insulin signaling impairment is the foremost biochemical mechanism underlying increased cardiovascular morbidity and mortality in atherosclerosis, T2DM, and metabolic syndrome. PMID:22202099

Dynamic Measurement of Tumor Vascular Permeability and Perfusion using a Hybrid System for Simultaneous Magnetic Resonance and Fluorescence Imaging.

PubMed

Ren, Wuwei; Elmer, Andreas; Buehlmann, David; Augath, Mark-Aurel; Vats, Divya; Ripoll, Jorge; Rudin, Markus

2016-04-01

Assessing tumor vascular features including permeability and perfusion is essential for diagnostic and therapeutic purposes. The aim of this study was to compare fluorescence and magnetic resonance imaging (MRI)-based vascular readouts in subcutaneously implanted tumors in mice by simultaneous dynamic measurement of tracer uptake using a hybrid fluorescence molecular tomography (FMT)/MRI system. Vascular permeability was measured using a mixture of extravascular imaging agents, GdDOTA and the dye Cy5.5, and perfusion using a mixture of intravascular agents, Endorem and a fluorescent probe (Angiosense). Dynamic fluorescence reflectance imaging (dFRI) was integrated into the hybrid system for high temporal resolution. Excellent correspondence between uptake curves of Cy5.5/GdDOTA and Endorem/Angiosense has been found with correlation coefficients R > 0.98. The two modalities revealed good agreement regarding permeability coefficients and centers-of-gravity of the imaging agent distribution. The FMT/dFRI protocol presented is able to accurately map physiological processes and poses an attractive alternative to MRI for characterizing tumor neoangiogenesis.

Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing

PubMed Central

Kolluru, Gopi Krishna; Bir, Shyamal C.; Kevil, Christopher G.

2012-01-01

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin. Patients with DM are frequently afflicted with ischemic vascular disease or wound healing defect. It is well known that type 2 DM causes amplification of the atherosclerotic process, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. These complications ultimately lead to impairment of neovascularization and diabetic wound healing. Therapeutic angiogenesis remains an attractive treatment modality for chronic ischemic disorders including PAD and/or diabetic wound healing. Many experimental studies have identified better approaches for diabetic cardiovascular complications, however, successful clinical translation has been limited possibly due to the narrow therapeutic targets of these agents or the lack of rigorous evaluation of pathology and therapeutic mechanisms in experimental models of disease. This paper discusses the current body of evidence identifying endothelial dysfunction and impaired angiogenesis during diabetes. PMID:22611498

The challenge of methicillin-resistant Staphylococcus aureus prevention in hemodialysis therapy.

PubMed

Parker, Mark G; Doebbeling, Bradley N

2012-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) infections have challenged care process and resource utilization in the acute hospital care setting for nearly 30 years. These infections have become important causes of morbidity, mortality, and a source of concern in the primary and emergency care context over the past decade. As individuals receiving recurrent therapy with features of both ambulatory care and acute care, hemodialysis patients are exposed to numerous opportunities for MRSA acquisition. Surprisingly, high prevalence rates for MRSA colonization have been demonstrated for both hemodialysis patients and their care providers. The necessity of vascular access and the persistent high prevalence of endovascular catheter use among patients repeatedly exposed to healthcare settings provide the perfect milieu for the troubling rates of MRSA infection, particularly bloodstream infections, in outpatient dialysis care. Dialysis industry shifts, including increased requirements for compliance and reporting in other areas of dialysis care, tax resources for infection prevention processes. Multifaceted strategies that include reassessment of vascular access care, attention to the interruption of MRSA transmission dynamics, and emphasis on organizational learning processes are needed to accomplish a meaningful reduction in the morbidity, mortality, and cost associated with MRSA infections in dialysis care. © 2011 Wiley Periodicals, Inc.

Alteration of Endothelins: A Common Pathogenetic Mechanism in Chronic Diabetic Complications

PubMed Central

Khan, Zia Ali; Cukiernik, Mark; Fukuda, Gen; Chen, Shali; Mukherjee, Suranjana

2002-01-01

Endothelin (ET) peptides perform several physiological, vascular, and nonvascular functions and are widely distributed in a number of tissues. They are altered in several disease processes including diabetes. Alteration of ETs have been demonstrated in organs of chronic diabetic complications in both experimental and clinical studies. The majority of the effects of ET alteration in diabetes are due to altered vascular function. Furthermore, ET antagonists have been shown to prevent structural and functional changes induced by diabetes in animal models. This review discusses the contribution of ETs in the pathogenesis and the potential role of ET antagonism in the treatment of chronic diabetic complications. PMID:12546275

Endoscopic Management of Vascular Sinonasal Tumors, Including Angiofibroma.

PubMed

Snyderman, Carl H; Pant, Harshita

2016-06-01

The greatest challenge in the surgical treatment of angiofibromas is dealing with the hypervascularity of these tumors. Staging systems that take into account the vascularity of the tumor may be more prognostic. A variety of treatment strategies are used to deal with the vascularity of angiofibromas, including preoperative embolization, segmentation of the tumor into vascular territories, use of hemostatic tools, and staging of surgery. Even large angiofibromas with intracranial extension and residual vascularity can be successfully managed by a skull base team using endoscopic techniques. Copyright © 2016 Elsevier Inc. 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.

Toxicity of Vascular Disrupting Chemicals to Developing Zebrafish

EPA Science Inventory

Vascular development is integral to proper embryonic development and disruption of that process can have serious developmental consequences. We performed static 48-hr exposures of transgenic TG(kdr:EGFP)s843 zebrafish (Danio rerio) embryos with the known vascular inhibitors Vatal...

Pattern and density of vascularization in mammalian testes, ovaries, and ovotestes.

PubMed

Lupiáñez, Darío G; Real, Francisca M; Dadhich, Rajesh K; Carmona, Francisco D; Burgos, Miguel; Barrionuevo, Francisco J; Jiménez, Rafael

2012-05-01

According to the classical paradigm, the vasculature of the embryonic testis is more dense and complex than that of the ovary, but recent studies based on whole-mount detection of Caveolin-1 (CAV1) as an endothelial cell marker, have suggested that the level of ovarian vascularization is higher than previously assumed. However, this new hypothesis has been neither tested using alternative methodology nor investigated in other mammalian species. In this paper, we have studied the vascularization process in the gonads of males and females of two mammalian species, the mouse (Mus musculus) and the Iberian mole (Talpa occidentalis). Our results show that the pattern of testis vascularization is very well conserved among mammals, including both pre- and postnatal stages of development and, at least in the mole, it is conserved irrespectively of whether the testicular tissue is XY or XX. We have shown that CAV1 is present not only in endothelial cells but also in prefollicular oocytes and in an ovarian population of somatic cortical cells. These data clearly establish that: (1) according to the classical hypothesis, the degree of vascularization of the developing ovary is lower than that of the testis, (2) ovarian vascularization is also evolutionarily conserved as it occurs similarly both in moles and in mice, and (3) that the degree of vascular development of the mammalian ovary is age-dependent increasing significatively at puberty. The expression of CAV1 in the ovary of most animal taxa, from nematodes to mammals, strongly suggests a role for this gene in the female meiosis. © 2012 WILEY PERIODICALS, INC.

Antiangiogenic Therapy for Ischemic Retinopathies

PubMed Central

Al-Latayfeh, Motasem; Silva, Paolo S.; Sun, Jennifer K.; Aiello, Lloyd Paul

2012-01-01

Neovascularization is a common pathological process in various retinal vascular disorders including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). The development of neovascular vessels may lead to complications such as vitreous hemorrhage, fibrovascular tissue formation, and traction retinal detachments. Ultimately, irreversible vision loss may result. Various proangiogenic factors are involved in these complex processes. Different antiangiogenic drugs have been formulated in an attempt treat these vascular disorders. One factor that plays a major role in the development of retinal neovascularization is vascular endothelial growth factor (VEGF). Anti-VEGF agents are currently FDA approved for the treatment of AMD and RVO. They are also extensively used as an off-label treatment for diabetic macular edema (DME), proliferative DR, and neovascular glaucoma. However, at this time, the long-term safety of chronic VEGF inhibition has not been extensively evaluated. A large and rapidly expanding body of research on angiogenesis is being conducted at multiple centers across the globe to determine the exact contributions and interactions among a variety of angiogenic factors in an effort to determine the therapeutic potential of antiangiogenic agent in the treatment of a variety of retinal diseases. PMID:22675660

MiR-144 regulates hematopoiesis and vascular development by targeting meis1 during zebrafish development.

PubMed

Su, Zhenhong; Si, Wenxia; Li, Lei; Zhou, Bisheng; Li, Xiuchun; Xu, Yan; Xu, Chengqi; Jia, Haibo; Wang, Qing K

2014-04-01

Hematopoiesis is a dynamic process by which peripheral blood lineages are developed. It is a process tightly regulated by many intrinsic and extrinsic factors, including transcriptional factors and signaling molecules. However, the epigenetic regulation of hematopoiesis, for example, regulation via microRNAs (miRNAs), remains incompletely understood. Here we show that miR-144 regulates hematopoiesis and vascular development in zebrafish. Overexpression of miR-144 inhibited primitive hematopoiesis as demonstrated by a reduced number of circulating blood cells, reduced o-dianisidine staining of hemoglobin, and reduced expression of hbαe1, hbβe1, gata1 and pu.1. Overexpression of miR-144 also inhibited definitive hematopoiesis as shown by reduced expression of runx1 and c-myb. Mechanistically, miR-144 regulates hematopoiesis by repressing expression of meis1 involved in hematopoiesis. Both real-time RT-PCR and Western blot analyses showed that overexpression of miR-144 repressed expression of meis1. Bioinformatic analysis predicts a target binding sequence for miR-144 at the 3'-UTR of meis1. Deletion of the miR-144 target sequence eliminated the repression of meis1 expression mediated by miR-144. The miR-144-mediated abnormal phenotypes were partially rescued by co-injection of meis1 mRNA and could be almost completely rescued by injection of both meis1 and gata1 mRNA. Finally, because meis1 is involved in vascular development, we tested the effect of miR-144 on vascular development. Overexpression of miR-144 resulted in abnormal vascular development of intersegmental vessels in transgenic zebrafish with Flk1p-EGFP, and the defect was rescued by co-injection of meis1 mRNA. These findings establish miR-144 as a novel miRNA that regulates hematopoiesis and vascular development by repressing expression of meis1. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biology of vascular malformations of the brain.

PubMed

Leblanc, Gabrielle G; Golanov, Eugene; Awad, Issam A; Young, William L

2009-12-01

This review discusses recent research on the genetic, molecular, cellular, and developmental mechanisms underlying the etiology of vascular malformations of the brain (VMBs), including cerebral cavernous malformation, sporadic brain arteriovenous malformation, and the arteriovenous malformations of hereditary hemorrhagic telangiectasia. Summary of Review- The identification of gene mutations and genetic risk factors associated with cerebral cavernous malformation, hereditary hemorrhagic telangiectasia, and sporadic arteriovenous malformation has enabled the development of animal models for these diseases and provided new insights into their etiology. All of the genes associated with VMBs to date have known or plausible roles in angiogenesis and vascular remodeling. Recent work suggests that the angiogenic process most severely disrupted by VMB gene mutation is that of vascular stabilization, the process whereby vascular endothelial cells form capillary tubes, strengthen their intercellular junctions, and recruit smooth muscle cells to the vessel wall. In addition, there is now good evidence that in some cases, cerebral cavernous malformation lesion formation involves a genetic 2-hit mechanism in which a germline mutation in one copy of a cerebral cavernous malformation gene is followed by a somatic mutation in the other copy. There is also increasing evidence that environmental second hits can produce lesions when there is a mutation to a single allele of a VMB gene. Recent findings begin to explain how mutations in VMB genes render vessels vulnerable to rupture when challenged with other inauspicious genetic or environmental factors and have suggested candidate therapeutics. Understanding of the cellular mechanisms of VMB formation and progression in humans has lagged behind that in animal models. New knowledge of lesion biology will spur new translational work. Several well-established clinical and genetic database efforts are already in place, and further progress will be facilitated by collaborative expansion and standardization of these.

Initial experience with the Cardiva Boomerang vascular closure device in diagnostic catheterization.

PubMed

Doyle, Brendan J; Godfrey, Michael J; Lennon, Ryan J; Ryan, James L; Bresnahan, John F; Rihal, Charanjit S; Ting, Henry H

2007-02-01

The authors studied the safety and efficacy of the Cardiva Boomerang vascular closure device in patients undergoing diagnostic cardiac catheterization. Conventional vascular closure devices (sutures, collagen plugs, or metal clips) have been associated with catastrophic complications including arterial occlusion and foreign body infections; furthermore, they cannot be utilized in patients with peripheral vascular disease or vascular access site in a vessel other than the common femoral artery. The Cardiva Boomerang device facilitates vascular hemostasis without leaving any foreign body behind at the access site, can be used in peripheral vascular disease, and can be used in vessels other than the common femoral artery A total of 96 patients undergoing transfemoral diagnostic cardiac catheterization were included in this study, including 25 (26%) patients with contraindications to conventional closure devices. Femoral angiography was performed prior to deployment of the Cardiva Boomerang closure device. Patients were ambulated at 1 hr after hemostasis was achieved. The device was successfully deployed and hemostasis achieved with the device alone in 95 (99%) patients. The device failed to deploy in 1 (1%) patient and required conversion to standard manual compression. Minor complications were observed in 5 (5%) patients. No patients experienced major complications including femoral hematoma > 4 cm, red blood cell transfusion, retroperitoneal bleed, arteriovenous fistula, pseudoaneurysm, infection, arterial occlusion, or vascular surgery. The Cardiva Boomerang device is safe and effective in patients undergoing diagnostic cardiac catheterization using the transfemoral approach, facilitating early ambulation with low rates of vascular complications. (c) 2006 Wiley-Liss, Inc.

Retinal vascular imaging in early life: insights into processes and risk of cardiovascular disease

PubMed Central

Li, Ling‐Jun; Ikram, Mohammad Kamran

2015-01-01

Abstract Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. In recent years, studies have shown that the origins of CVD may be traced to vascular and metabolic processes in early life. Retinal vascular imaging is a new technology that allows detailed non‐invasive in vivo assessment and monitoring of the microvasculature. In this systematic review, we described the application of retinal vascular imaging in children and adolescents, and we examined the use of retinal vascular imaging in understanding CVD risk in early life. We reviewed all publications with quantitative retinal vascular assessment in two databases: PubMed and Scopus. Early life CVD risk factors were classified into four groups: birth risk factors, environmental risk factors, systemic risk factors and conditions linked to future CVD development. Retinal vascular changes were associated with lower birth weight, shorter gestational age, low‐fibre and high‐sugar diet, lesser physical activity, parental hypertension history, childhood hypertension, childhood overweight/obesity, childhood depression/anxiety and childhood type 1 diabetes mellitus. In summary, there is increasing evidence supporting the view that structural changes in the retinal microvasculature are associated with CVD risk factors in early life. Thus, the retina is a useful site for pre‐clinical assessment of microvascular processes that may underlie the future development of CVD in adulthood. PMID:26435039

Imaging of cerebrovascular pathology in animal models of Alzheimer's disease

PubMed Central

Klohs, Jan; Rudin, Markus; Shimshek, Derya R.; Beckmann, Nicolau

2014-01-01

In Alzheimer's disease (AD), vascular pathology may interact with neurodegeneration and thus aggravate cognitive decline. As the relationship between these two processes is poorly understood, research has been increasingly focused on understanding the link between cerebrovascular alterations and AD. This has at last been spurred by the engineering of transgenic animals, which display pathological features of AD and develop cerebral amyloid angiopathy to various degrees. Transgenic models are versatile for investigating the role of amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic concepts. In addition, research has benefited from the development of novel imaging techniques, which are capable of characterizing vascular pathology in vivo. They provide vascular structural read-outs and have the ability to assess the functional consequences of vascular dysfunction as well as to visualize and monitor the molecular processes underlying these pathological alterations. This article focusses on recent in vivo small animal imaging studies addressing vascular aspects related to AD. With the technical advances of imaging modalities such as magnetic resonance, nuclear and microscopic imaging, molecular, functional and structural information related to vascular pathology can now be visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid-β (Aβ) deposition as well as Aβ transport pathways have been shown to be useful to characterize their dynamics and to elucidate their role in the development of cerebral amyloid angiopathy and AD. Structural and functional imaging read-outs have been employed to describe the deleterious affects of Aβ on vessel morphology, hemodynamics and vascular integrity. More recent imaging studies have also addressed how inflammatory processes partake in the pathogenesis of the disease. Moreover, imaging can be pivotal in the search for novel therapies targeting the vasculature. PMID:24659966

Childhood Vascular Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Vascular tumors in children are a spectrum of diseases that includes infantile, congenital, spindle cell and epithelioid hemangiomas, as well as angiofibromas, hemangioendotheliomas, and angiosarcomas. Get detailed information about the many types of vascular tumors including clinical presentation, diagnosis, prognosis and treatment in this summary for clinicians.

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

Immediate and long-term consequences of vascular toxicity during zebrafish development

EPA Science Inventory

Proper formation of the vascular system is necessary for embryogenesis, and chemical disruption of vascular development may be a key event driving developmental toxicity. In order to test the effect of environmental chemicals on this critical process, we developed a quantitative ...

Haptoglobin Preserves Vascular Nitric Oxide Signaling during Hemolysis.

PubMed

Schaer, Christian A; Deuel, Jeremy W; Schildknecht, Daniela; Mahmoudi, Leila; Garcia-Rubio, Ines; Owczarek, Catherine; Schauer, Stefan; Kissner, Reinhard; Banerjee, Uddyalok; Palmer, Andre F; Spahn, Donat R; Irwin, David C; Vallelian, Florence; Buehler, Paul W; Schaer, Dominik J

2016-05-15

Hemolysis occurs not only in conditions such as sickle cell disease and malaria but also during transfusion of stored blood, extracorporeal circulation, and sepsis. Cell-free Hb depletes nitric oxide (NO) in the vasculature, causing vasoconstriction and eventually cardiovascular complications. We hypothesize that Hb-binding proteins may preserve vascular NO signaling during hemolysis. Characterization of an archetypical function by which Hb scavenger proteins could preserve NO signaling during hemolysis. We investigated NO reaction kinetics, effects on arterial NO signaling, and tissue distribution of cell-free Hb and its scavenger protein complexes. Extravascular translocation of cell-free Hb into interstitial spaces, including the vascular smooth muscle cell layer of rat and pig coronary arteries, promotes vascular NO resistance. This critical disease process is blocked by haptoglobin. Haptoglobin does not change NO dioxygenation rates of Hb; rather, the large size of the Hb:haptoglobin complex prevents Hb extravasation, which uncouples NO/Hb interaction and vasoconstriction. Size-selective compartmentalization of Hb functions as a substitute for red blood cells after hemolysis and preserves NO signaling in the vasculature. We found that evolutionarily and structurally unrelated Hb-binding proteins, such as PIT54 found in avian species, functionally converged with haptoglobin to protect NO signaling by sequestering cell-free Hb in large protein complexes. Sequential compartmentalization of Hb by erythrocytes and scavenger protein complexes is an archetypical mechanism, which may have supported coevolution of hemolysis and normal vascular function. Therapeutic supplementation of Hb scavengers may restore vascular NO signaling and attenuate disease complications in patients with hemolysis.

Management of Low-Flow Vascular Malformations: Clinical Presentation, Classification, Patient Selection, Imaging and Treatment

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

McCafferty, Ian, E-mail: ian.mccafferty@uhb.nhs.uk

This review article aims to give an overview of the current state of imaging, patient selection, agents and techniques used in the management of low-flow vascular malformations. The review includes the current classifications for low-flow vascular malformations including the 2014 updates. Clinical presentation and assessment is covered with a detailed section on the common sclerosant agents used to treat low-flow vascular malformations, including dosing and common complications. Imaging is described with a guide to a simple stratification of the use of imaging for diagnosis and interventional techniques.

The 50 most influential original articles in vascular surgery during the last 25 years.

PubMed

Stegall, Frank; Corey, Michael; Dattilo, Jeffery

2014-09-01

We have compiled a list of the 50 most-cited original articles in the field of vascular surgery during the last 25 years to highlight the important changes in practice that have occurred during this interval and provide surgical trainees in vascular surgery ready access to such influential articles. A Web of Knowledge Citation Index Search was performed in December 2013 for the most-cited journal articles in the discipline of vascular surgery. We searched the term "vascular" in the cited reference search area and then further narrowed our results to exclude all categories except "surgery," "general internal medicine," and "cardiac/cardiovascular systems." We included only documents labeled as "articles" and those published in English. Articles dealing with cardiac surgery, interventional cardiology, and cardiovascular biology were excluded. Our search period was from January 1, 1988, through December 3, 2013. The 50 most frequently cited works were chosen, and a citation density was calculated for each, reflecting the average number of citations each received per year since publication. The articles were then sorted into a defined category, based on the clinical subject to which they pertained. The Citation Index Search resulted 80,379 articles, of which the top 50 were indexed and organized according to their citation density and area within the scope of clinical vascular surgery. The number of citations ranged from 218 to 3593. The median citation density was 50.2 (range, 11.3-201.3). This report is a representation of the most-cited original publications in the field of clinical vascular surgery during the last 25 years. This is an effort to highlight the seminal works that have shaped the discipline of vascular surgery as well as to provide a concise reference list for the surgical trainee in the process of his or her education. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

PubMed

Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

2016-01-01

Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions associate with deeper vessel injury affecting vascular smooth muscle cells.

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke

PubMed Central

Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

2016-01-01

Purpose Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Methods Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3–7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Results Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Conclusions Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions associate with deeper vessel injury affecting vascular smooth muscle cells. PMID:26815842

Imaging the floor of the mouth and the sublingual space.

PubMed

La'porte, Sarah J; Juttla, Jaspal K; Lingam, Ravi K

2011-01-01

A wide range of pathologic processes may involve the floor of the mouth, the part of the oral cavity that is located beneath the tongue. They include lesions that arise uniquely in this location (eg, ranula, submandibular duct obstruction) as well as various malignancies, inflammatory processes, and vascular abnormalities that may also occur elsewhere in the head and neck. Some lesions that arise in superficial tissues such as the mucosa may be easily diagnosed at physical examination. However, computed tomography, magnetic resonance imaging, or ultrasonography may be necessary for a reliable assessment of lesion extension to deeper structures. In such cases, knowledge of the complex muscular, vascular, glandular, ductal, and neural anatomy of the region is important for accurate diagnosis and treatment planning. Familiarity with the radiologic imaging appearances of the floor of the mouth and recognition of anatomic landmarks such as the mylohyoid and hyoglossus muscles are especially useful for localizing disease within this region.

Modeling and processing of laser Doppler reactive hyperaemia signals

NASA Astrophysics Data System (ADS)

Humeau, Anne; Saumet, Jean-Louis; L'Huiller, Jean-Pierre

2003-07-01

Laser Doppler flowmetry is a non-invasive method used in the medical domain to monitor the microvascular blood cell perfusion through tissue. Most commercial laser Doppler flowmeters use an algorithm calculating the first moment of the power spectral density to give the perfusion value. Many clinical applications measure the perfusion after a vascular provocation such as a vascular occlusion. The response obtained is then called reactive hyperaemia. Target pathologies include diabetes, hypertension and peripheral arterial occlusive diseases. In order to have a deeper knowledge on reactive hyperaemia acquired by the laser Doppler technique, the present work first proposes two models (one analytical and one numerical) of the observed phenomenon. Then, a study on the multiple scattering between photons and red blood cells occurring during reactive hyperaemia is carried out. Finally, a signal processing that improves the diagnosis of peripheral arterial occlusive diseases is presented.

Vascular system modeling in parallel environment - distributed and shared memory approaches

PubMed Central

Jurczuk, Krzysztof; Kretowski, Marek; Bezy-Wendling, Johanne

2011-01-01

The paper presents two approaches in parallel modeling of vascular system development in internal organs. In the first approach, new parts of tissue are distributed among processors and each processor is responsible for perfusing its assigned parts of tissue to all vascular trees. Communication between processors is accomplished by passing messages and therefore this algorithm is perfectly suited for distributed memory architectures. The second approach is designed for shared memory machines. It parallelizes the perfusion process during which individual processing units perform calculations concerning different vascular trees. The experimental results, performed on a computing cluster and multi-core machines, show that both algorithms provide a significant speedup. PMID:21550891

Vascular oxidative stress: a key factor in the development of hypertension associated with ethanol consumption.

PubMed

Ceron, Carla S; Marchi, Katia C; Muniz, Jaqueline J; Tirapelli, Carlos R

2014-01-01

The observation that the excessive consumption of ethyl alcohol (ethanol) is associated with high blood pressure is nearing its centennial mark. Mechanisms linking ethanol consumption and hypertension are complex and not fully understood. It is established that chronic ethanol consumption leads to hypertension and that this process is a multimediated event involving increased sympathetic activity, stimulation of the renin-angiotensin-aldosterone system with a subsequent increase in vascular oxidative stress and endothelial dysfunction. Under physiological conditions, reactive oxygen species (ROS) play an important role as a signaling molecule in the control of vascular tone and endothelial function. Increased ROS bioavailability is associated with important processes underlying vascular injury in cardiovascular disease such as endothelial dysfunction, vascular remodeling, and inflammation. Studies focusing on molecular mechanisms showed a link between overproduction of ROS in the vasculature and ethanol-induced hypertension. Of the ROS generated in vascular cells, superoxide anion (O2(-)) and hydrogen peroxide (H2O2) appear to be especially important. Ethanol-mediated generation of O2(-) and H2O2 in vascular tissues is associated with elevations in intracellular calcium ([Ca(2+)]i), reduced nitric oxide (NO) bioavailability, endothelial dysfunction and vasoconstriction. O2(-) can also act as a vascular signaling molecule regulating signaling pathways that lead to vascular contraction. Thus, through increased generation of ROS and activation of redox-sensitive pathways, ethanol induces vascular dysfunction, a response that might contribute to the hypertension associated with ethanol consumption. The present article reviews the role of ROS in vascular (patho)biology of ethanol.

7 CFR 51.3416 - Classification of defects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Maximum allowed for U.S. No. 2 processing Occurring outside of or not entirely confined to the vascular ring Internal Black Spot, Internal Discoloration, Vascular Browning, Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5% waste 10% waste. Occurring entirely within the vascular ring Hollow Heart or...

[Exercise for prevention of osteoporosis and other lifestyle-related diseases].

PubMed

Suzuki, Takao

2011-05-01

The prevalence of lifestyle-related diseases including hypertension, dyslipidemia (hyperlipidemia) and diabetes increases with aging, and all these conditions are risk factors of arteriosclerotic diseases such as cerebrovascular event (stroke) and myocardial infarction. The term "metabolic domino" has been used to describe the collective concept of the development and progression of these lifestyle-related diseases, the sequence of events, and the progression process of complications. Like the first tile of a domino toppling game, undesirable lifestyle such as overeating and underexercising first triggers obesity, and is followed in succession by onset of an insulin resistance state (underlied by a genetic background indigenous to Japanese) , hypertension, hyperlipidemia, and further postprandial hyperglycemia (the pre-diabetic state) , the so-called metabolic syndrome, at around the same time. On the other hand, apart from the other lifestyle-related diseases, the prevalence of osteoporosis also increases rapidly accompanying aging. Osteoporosis is known to be strongly related to disorders due to the metabolic domino such as arteriosclerosis and vascular calcification, and a new disease category called "osteo-vascular interaction" has attracted attention recently. Regarding "osteo-vascular interaction" , a close relation between bone density loss or osteoporotic changes and vascular lesion-associated lifestyle-related diseases such as hypertension, dyslipidemia and diabetes has been reported. Therefore, as a common preventive factor for bone mass loss or osteoporosis and lifestyle-related diseases including hypertension, dyslipidemia and diabetes (osteo-vascular interaction) , exercise has been recognized anew as an important non-pharmaceutical therapy that should take top priority. This article overviews the evidence of exercise therapy for the prevention of osteoporosis and other lifestyle-related diseases, from the viewpoint of health promotion, especially of the skeletal system (motor system) .

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

Standing balance in people with trans-tibial amputation due to vascular causes: A literature review.

PubMed

Seth, Mayank; Lamberg, Eric

2017-08-01

Balance is an important variable to consider during the rehabilitation process of individuals with trans-tibial amputation. Limited evidence exists on the balance abilities of people with trans-tibial amputation due to vascular causes. The purpose of this article is to review literature and determine if standing balance is diminished in people with trans-tibial amputation due to vascular causes. Literature review. Data were obtained from PubMed, Google Scholar, OandP.org , CINHAL, and Science Direct. Studies were selected only if they included standing balance assessment of people with unilateral trans-tibial amputation due to vascular causes. The review yielded seven articles that met the inclusion criteria. The general test methodology required participants to stand still on force platforms, with feet together, while center of pressure or postural sway was recorded. According to the findings of this review, individuals with trans-tibial amputees due to vascular causes have diminished balance abilities. Limited evidence suggests their balance might be further diminished as compared to individuals with trans-tibial amputation due to trauma. Although the evidence is limited, because of the underlying pathology and presence of comorbidities in individuals with trans-tibial amputation due to vascular causes, one cannot ignore these findings, as even a minor injury from a fall may develop into a non-healing ulcer and affect their health and well-being more severely than individuals with trans-tibial amputation due to trauma. Clinical relevance Individuals with trans-tibial amputation due to vascular causes have diminished balance abilities compared to healthy individuals and individuals with trans-tibial amputation due to trauma. This difference should be considered when designing and fabricating prostheses. Prosthetists and rehabilitation clinicians should consider designing amputation cause-specific rehabilitation interventions, focussing on balance and other functional limitations related to comorbidities of amputation.

Gastrin-releasing peptide induces monocyte adhesion to vascular endothelium by upregulating endothelial adhesion molecules

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

Kim, Mi-Kyoung; Park, Hyun-Joo; Department of Dental Pharmacology, BK21 PLUS Project, School of Dentistry, Pusan National University, Yangsan 626-870

Gastrin-releasing peptide (GRP) is a neuropeptide that plays roles in various pathophysiological conditions including inflammatory diseases in peripheral tissues; however, little is known about whether GRP can directly regulate endothelial inflammatory processes. In this study, we showed that GRP promotes the adhesion of leukocytes to human umbilical vein endothelial cells (HUVECs) and the aortic endothelium. GRP increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by activating nuclear factor-κB (NF-κB) in endothelial cells. In addition, GRP activated extracellular signal-regulated kinase 1/2 (ERK1/2), p38MAPK, and AKT, and the inhibition of these signaling pathways significantly reduced GRP-inducedmore » monocyte adhesion to the endothelium. Overall, our results suggested that GRP may cause endothelial dysfunction, which could be of particular relevance in the development of vascular inflammatory disorders. - Highlights: • GRP induces adhesion of monocytes to vascular endothelium. • GRP increases the expression of endothelial adhesion molecules through the activation of NF-κB. • ERK1/2, p38MAPK, and Akt pathways are involved in the GRP-induced leukocyte adhesiveness to endothelium.« less

Pathophysiological mechanisms of high-intensity focused ultrasound-mediated vascular occlusion and relevance to non-invasive fetal surgery

PubMed Central

Shaw, C. J.; ter Haar, G. R.; Rivens, I. H.; Giussani, D. A.; Lees, C. C.

2014-01-01

High-intensity focused ultrasound (HIFU) is a non-invasive technology, which can be used occlude blood vessels in the body. Both the theory underlying and practical process of blood vessel occlusion are still under development and relatively sparse in vivo experimental and therapeutic data exist. HIFU would however provide an alternative to surgery, particularly in circumstances where serious complications inherent to surgery outweigh the potential benefits. Accordingly, the HIFU technique would be of particular utility for fetal and placental interventions, where open or endoscopic surgery is fraught with difficulty and likelihood of complications including premature delivery. This assumes that HIFU could be shown to safely and effectively occlude blood vessels in utero. To understand these mechanisms more fully, we present a review of relevant cross-specialty literature on the topic of vascular HIFU and suggest an integrative mechanism taking into account clinical, physical and engineering considerations through which HIFU may produce vascular occlusion. This model may aid in the design of HIFU protocols to further develop this area, and might be adapted to provide a non-invasive therapy for conditions in fetal medicine where vascular occlusion is beneficial. PMID:24671935

Adolescents with vascular frontal lesion: A neuropsychological follow up case study.

PubMed

Chávez, Clara L; Yáñez, Guillermina; Catroppa, Cathy; Rojas, Sulema; Escartin, Erick; Hearps, Stephen J C; García, Antonio

2016-01-01

The objective of this research was to identify clinically significant changes in cognitive functions in three adolescents who underwent surgery for resection of a focal vascular lesion in the frontal lobe. Cognitive functions, executive function, behavior regulation, emotion regulation, and social abilities were assessed prior to surgery, six and 24 months post-discharge. Significant clinical changes were observed during all the assessments. Cognitive changes after surgery are not homogeneous. Most of the significant clinical changes were improvements. Especially the significant clinical changes presented in EF domains were only improvements; these results suggest that EF were affected by the vascular lesion and benefitted by the surgery. After resection of a vascular lesion between 15 and 16 years of age the affected executive functions can continue the maturation process. Our results highlight the importance that assessments must include emotional aspects, even if deficits in these domains are not presented in the acute phase. Rehabilitation methods should promote the development of skills that help patients and their families to manage the emotional and behavioral changes that emerge once they are discharged from the hospital. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Ubiquitin carboxyl terminal hydrolase L1 negatively regulates TNF{alpha}-mediated vascular smooth muscle cell proliferation via suppressing ERK activation

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

Ichikawa, Tomonaga; Li, Jinqing; Dong, Xiaoyu

2010-01-01

Deubiquitinating enzymes (DUBs) appear to be critical regulators of a multitude of processes such as proliferation, apoptosis, differentiation, and inflammation. We have recently demonstrated that a DUB of ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) inhibits vascular lesion formation via suppressing inflammatory responses in vasculature. However, the precise underlying mechanism remains to be defined. Herein, we report that a posttranscriptional up-regulation of UCH-L1 provides a negative feedback to tumor necrosis factor alpha (TNF{alpha})-mediated activation of extracellular signal-regulated kinases (ERK) and proliferation in vascular smooth muscle cells (VSMCs). In rat adult VSMCs, adenoviral over-expression of UCH-L1 inhibited TNF{alpha}-induced activation of ERK andmore » DNA synthesis. In contrast, over-expression of UCH-L1 did not affect platelet derived growth factor (PDGF)-induced VSMC proliferation and activation of growth stimulating cascades including ERK. TNF{alpha} hardly altered UCH-L1 mRNA expression and stability; however, up-regulated UCH-L1 protein expression via increasing UCH-L1 translation. These results uncover a novel mechanism by which UCH-L1 suppresses vascular inflammation.« less

Microvascular Remodeling and Wound Healing: A Role for Pericytes

PubMed Central

Dulmovits, Brian M.; Herman, Ira M.

2012-01-01

Physiologic wound healing is highly dependent on the coordinated functions of vascular and non-vascular cells. Resolution of tissue injury involves coagulation, inflammation, formation of granulation tissue, remodeling and scarring. Angiogenesis, the growth of microvessels the size of capillaries, is crucial for these processes, delivering blood-borne cells, nutrients and oxygen to actively remodeling areas. Central to angiogenic induction and regulation is microvascular remodeling, which is dependent upon capillary endothelial cell and pericyte interactions. Despite our growing knowledge of pericyte-endothelial cell crosstalk, it is unclear how the interplay among pericytes, inflammatory cells, glia and connective tissue elements shape microvascular injury response. Here, we consider the relationships that pericytes form with the cellular effectors of healing in normal and diabetic environments, including repair following injury and vascular complications of diabetes, such as diabetic macular edema and proliferative diabetic retinopathy. In addition, pericytes and stem cells possessing “pericyte-like” characteristics are gaining considerable attention in experimental and clinical efforts aimed at promoting healing or eradicating ocular vascular proliferative disorders. As the origin, identification and characterization of microvascular pericyte progenitor populations remains somewhat ambiguous, the molecular markers, structural and functional characteristics of pericytes will be briefly reviewed. PMID:22750474

FGF-dependent metabolic control of vascular development

PubMed Central

Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-01-01

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822

FGF-dependent metabolic control of vascular development.

PubMed

Yu, Pengchun; Wilhelm, Kerstin; Dubrac, Alexandre; Tung, Joe K; Alves, Tiago C; Fang, Jennifer S; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G; Hirschi, Karen K; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-05-11

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes. Although much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism, little is understood about the role of fibroblast growth factors (FGFs) in this context. Here we identify FGF receptor (FGFR) signalling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signalling inputs results in decreased glycolysis, leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/Fgfr3 double mutant mice, while HK2 overexpression partly rescues the defects caused by suppression of FGF signalling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development.

Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

PubMed Central

Nicolosi, Pier Andrea; Tombetti, Enrico; Maugeri, Norma; Rovere-Querini, Patrizia; Brunelli, Silvia; Manfredi, Angelo A.

2016-01-01

Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc). The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment. PMID:27069480

Early events in geotropism of seedling shoots

NASA Technical Reports Server (NTRS)

Pickard, B. G.

1985-01-01

Developments during the first ten minutes of geotropic stimulation in plant seedling shoots are reviewed. Topics include induction and curvature; early processes; the relationship between auxin, electric field, calcium, and differential growth; gravity reception leading to Went-Cholodny transport; and comparison of root and shoot. Early processes reviewed are sedimentation of amyloplasts, release of ethylene, rise of electrical and auxin asymmetry, redistribution of calcium, asymmetric vascular transport, increase in tendency to deposit callose, and simulation of putative exocytotic voltage transients.

Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by Video-Rate Intravital Microscopy and 3D Image Processing.

PubMed

Pang, Yonggang; Tsigkou, Olga; Spencer, Joel A; Lin, Charles P; Neville, Craig; Grottkau, Brian

2015-10-01

Vascularization is a key challenge in tissue engineering. Three-dimensional structure and microcirculation are two fundamental parameters for evaluating vascularization. Microscopic techniques with cellular level resolution, fast continuous observation, and robust 3D postimage processing are essential for evaluation, but have not been applied previously because of technical difficulties. In this study, we report novel video-rate confocal microscopy and 3D postimage processing techniques to accomplish this goal. In an immune-deficient mouse model, vascularized bone tissue was successfully engineered using human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in a poly (D,L-lactide-co-glycolide) (PLGA) scaffold. Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in vivo to visualize the vascular structure in the engineered bone and the microcirculation of the blood cells. Postimage processing was applied to perform 3D image reconstruction, by analyzing microvascular networks and calculating blood cell viscosity. The 3D volume reconstructed images show that the hMSCs served as pericytes stabilizing the microvascular network formed by HUVECs. Using orthogonal imaging reconstruction and transparency adjustment, both the vessel structure and blood cells within the vessel lumen were visualized. Network length, network intersections, and intersection densities were successfully computed using our custom-developed software. Viscosity analysis of the blood cells provided functional evaluation of the microcirculation. These results show that by 8 weeks, the blood vessels in peripheral areas function quite similarly to the host vessels. However, the viscosity drops about fourfold where it is only 0.8 mm away from the host. In summary, we developed novel techniques combining intravital microscopy and 3D image processing to analyze the vascularization in engineered bone. These techniques have broad applicability for evaluating vascularization in other engineered tissues as well.

[Introduction and advantage analysis of the stepwise method for the construction of vascular trees].

PubMed

Zhang, Yan; Xie, Haiwei; Zhu, Kai

2010-08-01

A new method for constructing the model of vascular trees was proposed in this paper. By use of this method, the arterial trees in good agreement with the actual structure could be grown. In this process, all vessels in the vascular tree were divided into two groups: the conveying vessels, and the delivering branches. And different branches could be built by different ways. Firstly, the distributing rules of conveying vessels were ascertained by use of measurement data, and then the conveying vessels were constructed in accordance to the statistical rule and optimization criterion. Lastly, delivering branches were modeled by constrained constructive optimization (CCO) on the conveying vessel-trees which had already been generated. In order to compare the CCO method and stepwise method proposed here, two 3D arterial trees of human tongue were grown with their vascular tree having a special structure. Based on the corrosion casts of real arterial tree of human tongue, the data about the two trees constructed by different methods were compared and analyzed, including the averaged segment diameters at respective levels, the distribution and the diameters of the branches of first level at respective directions. The results show that the vascular tree built by stepwise method is more similar to the true arterial of human tongue when compared against the tree built by CCO method.

Microcomputed tomography characterization of neovascularization in bone tissue engineering applications.

PubMed

Young, Simon; Kretlow, James D; Nguyen, Charles; Bashoura, Alex G; Baggett, L Scott; Jansen, John A; Wong, Mark; Mikos, Antonios G

2008-09-01

Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs.

Intermountain Range plant names and symbols

Treesearch

A. Perry Plummer; Stephen B. Monsen; Richard Stevens

1977-01-01

This revised alphabetical list of botanical and common names of vascular plants that primarily grow on wildlands of the Intermountain region and adjacent areas has been assembled for use in quickly recording occurrence of plants in the field and for rapid machine processing of field data. Included are plants found in Utah, Nevada, southern Idaho, and Wyoming, and most...

Regulation of programmed cell death or apoptosis in atherosclerosis.

PubMed

Geng, Y J

1997-01-01

Intimal thickening caused by accumulation of cells, lipids, and connective tissue characterizes atherosclerosis, an arterial disease that leads to cardiac and cerebral infarction. Apoptosis, or genetically programmed cell death, is important for the development and morphogenesis of organs and tissues. As in other tissues, cells of cardiovascular tissues can undergo apoptosis. Increased apoptosis has been found in both human and animal atherosclerotic lesions, mediating tissue turnover and lesion development. In addition to vascular cells, many activated immune cells, mainly macrophages and T cells, are present in atherosclerotic lesions, where these cells produce biologically active substances such as the proinflammatory cytokines tumor necrosis factor, interleukin-1 (IL-1), and interferon-gamma. Simultaneous exposure to these cytokines may trigger apoptosis of vascular smooth muscle cells. The products of death-regulating genes including Fas/Fas ligand, members of IL-1 beta cysteinyl protease (caspase) family, the tumor suppressive gene p53, and the protooncogene c-myc have been found in vascular cells and may participate in the regulation of vascular apoptosis during the development of atherosclerosis. Abnormal occurrence of apoptosis may take place in atherosclerotic lesions, including attenuation or acceleration of the apoptotic death process. The former may cause an increase in the cellularity of the lesions, and the latter can reduce cellular components important for maintaining the integrity and stability of the plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of patients with atherosclerosis and its major complications, heart attack and stroke.

Biochemical factors modulating female genital sexual arousal physiology.

PubMed

Traish, Abdulmaged M; Botchevar, Ella; Kim, Noel N

2010-09-01

Female genital sexual arousal responses are complex neurophysiological processes consisting of central and peripheral components that occur following sexual stimulation. The peripheral responses in sexual arousal include genital vasocongestion, engorgement and lubrication resulting from a surge of vaginal and clitoral blood flow. These hemodynamic events are mediated by a host of neurotransmitters and vasoactive agents. To discuss the role of various biochemical factors modulating female genital sexual arousal responses. A comprehensive literature review was conducted using the PubMed database and citations were selected, based on topical relevance, and examined for study methodology and major findings. Data from peer-reviewed publications. Adrenergic as well as non-adrenergic non-cholinergic neurotransmitters play an important role in regulating genital physiological responses by mediating vascular and non-vascular smooth muscle contractility. Vasoactive peptides and neuropeptides also modulate genital sexual responses by regulating vascular and non-vascular smooth muscle cells and epithelial function. The endocrine milieu, particularly sex steroid hormones, is critical in the maintenance of tissue structure and function. Reduced levels of estrogens and androgen are associated with dramatic alterations in genital tissue structure, including the nerve network, as well as the response to physiological modulators. Furthermore, estrogen and androgen deficiency is associated with reduced expression of sex steroid receptors and most importantly with attenuated genital blood flow and lubrication in response to pelvic nerve stimulation. This article provides an integrated framework describing the physiological and molecular basis of various pathophysiological conditions associated with female genital sexual arousal dysfunction. © 2010 International Society for Sexual Medicine.

A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation

ClinicalTrials.gov

2017-08-08

Ischemia; Peripheral Arterial Disease; Peripheral Vascular Disease; Vascular Disease; Arterial Occlusive Disease; Arteriosclerosis; Atherosclerosis; Cardiovascular Disease; Pathologic Processes; Orthopedic Procedures; Amputation

Tumor Vessel Development and Expansion in Ewing's Sarcoma: A Review of the Vasculogenesis Process and Clinical Trials with Vascular-Targeting Agents

PubMed Central

Stewart, Keri S.; Kleinerman, Eugenie S.

2011-01-01

Ewing's sarcoma accounts for a disproportionately high portion of the overall pediatric mortality rate compared to its rare incidence in the pediatric population. Little progress has been made since the introduction of traditional chemotherapies, and understanding the biology of the tumor is critical for developing new therapies. Ewing's sarcomas rely on a functional vascular supply, which is formed by a combination of angiogenesis and vasculogenesis. Recent insights into the molecular regulation of bone marrow (BM) cell participation in vascular development have identified VEGF, SDF-1α, and DLL4 as critical players in the vasculogenesis process. Clinical trials using vascular targeting agents, specifically targeting VEGF or DLL4, are underway. PMID:21785569

Mechanical Properties of High Entropy Alloy Al0.1CoCrFeNi for Peripheral Vascular Stent Application.

PubMed

Alagarsamy, Karthik; Fortier, Aleksandra; Komarasamy, Mageshwari; Kumar, Nilesh; Mohammad, Atif; Banerjee, Subhash; Han, Hai-Chao; Mishra, Rajiv S

2016-12-01

High entropy alloys (HEAs) are new class of metallic materials with five or more principal alloying elements. Due to this distinct concept of alloying, the HEAs exhibit unique properties compared to conventional alloys. The outstanding properties of HEAs include increased strength, superior wear resistance, high temperature stability, increased fatigue properties, good corrosion, and oxidation resistance. Such characteristics of HEAs have generated significant interest among the scientific community. However, their applications are yet to be explored. This paper discusses the mechanical behavior and microstructure of Al 0.1 CoCrFeNi HEA subjected to thermo-mechanical processing, and its potential application in peripheral vascular stent implants that are prone to high failure rates. Results show that Al 0.1 CoCrFeNi alloy possesses characteristics that compare well against currently used stent materials and it can potentially find use in peripheral vascular stent implants and extend their life-cycle.

Implementation of a dedicated cardiovascular and stroke unit in a crowded emergency department of a tertiary public hospital in Brazil: effect on mortality rates.

PubMed

Nasi, Luiz A; Ferreira-Da-Silva, Andre L; Martins, Sheila C O; Furtado, Mariana V; Almeida, Andrea G; Brondani, Rosane; Wirth, Letícia; Kluck, Marisa; Polanczyk, Carisi A

2014-01-01

Emergency department (ED) care for acute vascular diseases faces the challenge of overcrowding. A vascular unit is a specialized, protocol-oriented unit in the ED with a team trained to manage acute vascular disorders, including stroke, coronary syndromes, pulmonary embolism (PE), and aortic diseases. The objective was to compare case fatality rates for selected cardiovascular conditions before and after the implementation of a vascular unit. Patients with the selected diagnoses admitted to the ED in two different time periods, 2002 through 2005 (before unit opening) and 2007 to 2010 (after vascular unit opening), were identified by ICD-10 codes, and their electronic records were reviewed. Case fatality rates were calculated and compared for both time periods. The period prior to unit implementation (2002 through 2005) included 4,164 patients, and the vascular unit period (2007 to 2010) included 6,280 patients. Overall, the case fatality rate for acute vascular conditions decreased from 9% to 7.3% with vascular unit implementation (p = 0.002). The in-hospital mortality rates for acute coronary syndrome (ACS) dropped from 6% to 3.8% (p = 0.003), and for acute PE dropped from 32.1% to 10.8% (p < 0.001). The stroke case-fatality rate did not decrease despite improvements in the quality of stroke health care indicators. The vascular unit strategy has the potential to reduce overall mortality for most acute vascular conditions. © 2013 by the Society for Academic Emergency Medicine.

Vascular-Derived Vegfa Promotes Cortical Interneuron Migration and Proximity to the Vasculature in the Developing Forebrain

PubMed Central

Barber, Melissa; Andrews, William D; Memi, Fani; Gardener, Phillip; Ciantar, Daniel; Tata, Mathew; Ruhrberg, Christiana; Parnavelas, John G

2018-01-01

Abstract Vascular endothelial growth factor (Vegfa) is essential for promoting the vascularization of the embryonic murine forebrain. In addition, it directly influences neural development, although its role in the forming forebrain is less well elucidated. It was recently suggested that Vegfa may influence the development of GABAergic interneurons, inhibitory cells with crucial signaling roles in cortical neuronal circuits. However, the mechanism by which it affects interneuron development remains unknown. Here we investigated the developmental processes by which Vegfa may influence cortical interneuron development by analyzing transgenic mice that ubiquitously express the Vegfa120 isoform to perturb its signaling gradient. We found that interneurons reach the dorsal cortex at mid phases of corticogenesis despite an aberrant vascular network. Instead, endothelial ablation of Vegfa alters cortical interneuron numbers, their intracortical distribution and spatial proximity to blood vessels. We show for the first time that vascular-secreted guidance factors promote early-migrating interneurons in the intact forebrain in vivo and identify a novel role for vascular-Vegfa in this process. PMID:29901792

Stroke from systemic vascular disorders in Saudi children. The devastating role of hypernatremic dehydration.

PubMed

Salih, Mustafa A; Zahraa, Jihad N; Al-Jarallah, Ahmed A; Alorainy, Ibrahim A; Hassan, Hamdy H

2006-03-01

Systemic vascular disorders, leading to childhood stroke, include volume depletion or systemic hypotension and hypernatremic dehydration. We describe 3 cases of stroke following systemic vascular disorders. These were diagnosed during a prospective and retrospective study on childhood stroke, which included 104 patients. Post-gastroenteritis hypernatremic dehydration is an important, potentially preventable, cause of stroke in Saudi children.

Activation of PPARδ counteracts angiotensin II-induced ROS generation by inhibiting rac1 translocation in vascular smooth muscle cells.

PubMed

Lee, Hanna; Ham, Sun Ah; Kim, Min Young; Kim, Jae-Hwan; Paek, Kyung Shin; Kang, Eun Sil; Kim, Hyo Jung; Hwang, Jung Seok; Yoo, Taesik; Park, Chankyu; Kim, Jin-Hoi; Lim, Dae-Seog; Han, Chang Woo; Seo, Han Geuk

2012-07-01

Angiotensin II (Ang II)-mediated modification of the redox milieu of vascular smooth muscle cells (VSMCs) has been implicated in several pathophysiological processes, including cell proliferation, migration and differentiation. In this study, we demonstrate that the peroxisome proliferator-activated receptor (PPAR) δ counteracts Ang II-induced production of reactive oxygen species (ROS) in VSMCs. Activation of PPARδ by GW501516, a specific ligand for PPARδ, significantly reduced Ang II-induced ROS generation in VSMCs. This effect was, however, reversed in the presence of small interfering (si)RNA against PPARδ. The marked increase in ROS levels induced by Ang II was also eliminated by the inhibition of phosphatidylinositol 3-kinase (PI3K) but not of protein kinase C, suggesting the involvement of the PI3K/Akt signalling pathway in this process. Accordingly, ablation of Akt with siRNA further enhanced the inhibitory effects of GW501516 in Ang II-induced superoxide production. Ligand-activated PPARδ also blocked Ang II-induced translocation of Rac1 to the cell membrane, inhibiting the activation of NADPH oxidases and consequently ROS generation. These results indicate that ligand-activated PPARδ plays an important role in the cellular response to oxidative stress by decreasing ROS generated by Ang II in vascular cells.

Salicylic acid prevents Trichoderma harzianum from entering the vascular system of roots.

PubMed

Alonso-Ramírez, Ana; Poveda, Jorge; Martín, Ignacio; Hermosa, Rosa; Monte, Enrique; Nicolás, Carlos

2014-10-01

Trichoderma is a soil-borne fungal genus that includes species with a significant impact on agriculture and industrial processes. Some Trichoderma strains exert beneficial effects in plants through root colonization, although little is known about how this interaction takes place. To better understand this process, the root colonization of wild-type Arabidopsis and the salicylic acid (SA)-impaired mutant sid2 by a green fluorescent protein (GFP)-marked Trichoderma harzianum strain was followed under confocal microscopy. Trichoderma harzianum GFP22 was able to penetrate the vascular tissue of the sid2 mutant because of the absence of callose deposition in the cell wall of root cells. In addition, a higher colonization of sid2 roots by GFP22 compared with that in Arabidopsis wild-type roots was detected by real-time polymerase chain reaction. These results, together with differences in the expression levels of plant defence genes in the roots of both interactions, support a key role for SA in Trichoderma early root colonization stages. We observed that, without the support of SA, plants were unable to prevent the arrival of the fungus in the vascular system and its spread into aerial parts, leading to later collapse. © 2014 BSPP AND JOHN WILEY & SONS LTD.

VESGEN Mapping of Bioactive Protection against Intestinal Inflammation: Application to Human Spaceflight and ISS Experiments

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, P. A.; Chen, X.; Kelly, C. P.; Reinecker, H. C.

2011-01-01

Challenges to successful space exploration and colonization include adverse physiological reactions to micro gravity and space radiation factors. Constant remodeling of the microvasculature is critical for tissue preservation, wound healing, and recovery after ischemia. Regulation of the vascular system in the intestine is particularly important to enable nutrient absorption while maintaining barrier function and mucosal defense against micro biota. Although tremendous progress has been made in understanding the molecular circuits regulating neovascularization, our knowledge of the adaptations of the vascular system to environmental challenges in the intestine remains incomplete. This is in part because of the lack of methods to observe and quantify the complex processes associated with vascular responses in vivo. Developed by GRC as a mature beta version, pre-release research software, VESsel GENeration Analysis (VESGEN) maps and quantifies the fractal-based complexity of vascular branching for novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and microvascular remodeling. Here we demonstrate that VESGEN can be used to characterize the dynamic vascular responses to acute intestinal inflammation and mucosal recovery from in vivo confocal microscopic 3D image series. We induced transient intestinal inflammation in mice by DSS treatment and investigated whether the ability of the pro biotic yeast Saccharomyces boulardii (Sb) to protect against intestinal inflammation was due to regulation of vascular remodeling. A primary characteristic of inflammation is excessive neovascularization (angiogenesis) resulting in fragile vessels prone to bleeding. Morphological parameters for triplicate specimens revealed that Sb treatment greatly reduced the inflammatory response of vascular networks by an average of 78%. This resulted from Sb inhibition of vascular endothelial growth factor receptor signaling, a major angiogenesis signaling pathway. It needs to be determined whether pro biotic yeast represents a promising approach to GI protection in space. GRC performed only the VESGEN post-testing analysis.

[Inflammatory process in atherogenesis: new facts about old flame].

PubMed

Vucević, Danijela; Radak, Dorde; Radosavljević, Tatjana; Mladenović, Dusan; Milovanović, Ivan

2012-01-01

INTRODUCTION. Atherosclerosis is a progressive, multifactorial, diffuse, multisystemic, chronic, inflammatory disease, which is manifested by disorders of vascular, immune and metabolic system. Pathogenesis of this disease is not fully understood. Endothelial Dysfunction and Inflammatory Process. Endothelial dysfunction is recognized as the crucial step in atherogenesis. A lot of studies have confirmed the involvement of various mediators of inflammation in initial proatherogenic processes, such as the upregulation of adhesion molecules on endothelial cells, binding of low density lipoproteins to endothelium, activation of macrophages and proliferation of vascular smooth muscle cells. Fatty stain and Inflammatory Process. Fatty stain consists of foam cell accumulation. After foam cell formation, mediators of inflammation initiate a series ofintracellular events that include the induction of inflammatory cytokines. Thus, a vicious circle of inflammation, modification of lipoproteins and further inflammation can be maintained in the artery. Transitory Lesion and Inflammatory Process. In transitory lesion intensive phagocytosis of oxidized low density lipoproteins additionally activates monocytes and macrophages and consequently facilitates and exacerbates the inflammatory response. Fibrotic Plaque and Inflammatory Process. Inflammatory process, matrix-degrading metalloproteinases activity, platelets aggregation and smooth muscle cells proliferation play a central role in development of fibrotic plaque. Complex Lesion and Inflammatory Process. It has been shown that inflammation is closely related to the development of atherosclerotic plaque rupture. The contribution of inflammatory process has become increasingly meaningful in understanding the initiation, progression and clinical manifestations ofatherosclerosis.

Regulation of endothelial Fas expression as a mechanism of promotion of vascular integrity by mural cells in tumors.

PubMed

Kamei, Ryosuke; Tanaka, Hiroyoshi Y; Kawano, Takao; Morii, Chiharu; Tanaka, Sayaka; Nishihara, Hiroshi; Iwata, Caname; Kano, Mitsunobu R

2017-05-01

Angiogenesis is a multi-step process that culminates in vascular maturation whereby nascent vessels stabilize to become functional, and mural cells play an essential role in this process. Recent studies have shown that mural cells in tumors also promote and maintain vascular integrity, with wide-reaching clinical implications including the regulation of tumor growth, metastases, and drug delivery. Various regulatory signaling pathways have been hitherto implicated, but whether regulation of Fas-dependent apoptotic mechanisms is involved has not yet been fully investigated. We first compared endothelial FAS staining in human pancreatic ductal adenocarcinomas and colon carcinomas and show that the latter, characterized by lower mural cell coverage of tumor vasculature, demonstrated higher expression of FAS than the former. Next, in an in vitro coculture system of MS-1 and 10T1/2 cells as endothelial and mural cells respectively, we show that mural cells decreased endothelial Fas expression. Then, in an in vivo model in which C26 colon carcinoma cells were inoculated together with MS-1 cells alone or with the further addition of 10T1/2 cells, we demonstrate that mural cells prevented hemorrhage. Finally, knockdown of endothelial Fas sufficiently recapitulated the protection against hemorrhage seen with the addition of mural cells. These results together suggest that regulation of endothelial Fas signaling is involved in the promotion of vascular integrity by mural cells in tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Implementing clinical process management of vascular wounds in a tertiary facility: impact evaluation of a performance improvement project.

PubMed

Avruscio, Giampiero; Tocco-Tussardi, Ilaria; Bordignon, Greta; Vindigni, Vincenzo

2017-01-01

Chronic vascular wounds have a significant economic and social impact on our society calling for allocation of a great deal of attention and resources. Efforts should be oriented toward the achievement of the most effective and efficient clinical management. The Angiology Unit at the University Hospital of Padova, Italy, developed a performance improvement project to enhance the quality of practice for vascular ulcers. The project consisted in a multistep process comprising a critical revision of the previous clinical process management, staff education, tightening connections between operators and services, and creation of a position for a wound care nurse. The previous standard of practice was modified according to the results of revision and the current evidence-based practice. The new standard of practice reached its full application in September 2015. The number of patients treated and the number of visits in 2015 remained almost unvaried from 2014. However, the total annual expenditure for treating vascular ulcers was reduced by ~60% from the previous year. Standardization of guidelines and practice is effective in creating an efficient clinical management and in reducing the economic burden of vascular ulcers.

Proangiogenic hematopoietic cells of monocytic origin: roles in vascular regeneration and pathogenic processes of systemic sclerosis.

PubMed

Yamaguchi, Yukie; Kuwana, Masataka

2013-02-01

New blood vessel formation is critical, not only for organ development and tissue regeneration, but also for various pathologic processes, such as tumor development and vasculopathy. The maintenance of the postnatal vascular system requires constant remodeling, which occurs through angiogenesis, vasculogenesis, and arteriogenesis. Vasculogenesis is mediated by the de novo differentiation of mature endothelial cells from endothelial progenitor cells (EPCs). Early studies provided evidence that bone marrow-derived CD14⁺ monocytes can serve as a subset of EPCs because of their expression of endothelial markers and ability to promote neovascularization in vitro and in vivo. However, the current consensus is that monocytic cells do not give rise to endothelial cells in vivo, but function as support cells, by promoting vascular formation and repair through their immediate recruitment to the site of vascular injury, secretion of proangiogenic factors, and differentiation into mural cells. These monocytes that function in a supporting role in vascular repair are now termed monocytic pro-angiogenic hematopoietic cells (PHCs). Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by excessive fibrosis and microvasculopathy, along with poor vascular formation and repair. We recently showed that in patients with SSc, circulating monocytic PHCs increase dramatically and have enhanced angiogenic potency. These effects may be induced in response to defective vascular repair machinery. Since CD14⁺ monocytes can also differentiate into fibroblast-like cells that produce extracellular matrix proteins, here we propose a new hypothesis that aberrant monocytic PHCs, once mobilized into circulation, may also contribute to the fibrotic process of SSc.

Fusion of uniluminal vascular spheroids: a model for assembly of blood vessels

PubMed Central

Fleming, Paul A.; Argraves, W. Scott; Gentile, Carmine; Neagu, Adrian; Forgacs, Gabor; Drake, Christopher J.

2010-01-01

Here, we evaluated the self-assembly properties of uniluminal vascular spheroids having outer layers of vascular smooth muscle cells and a contiguous inner layer of endothelial cells lining a central lumen. We showed that while pairs of uniluminal vascular spheroids suspended in culture medium fused to form a larger diameter spheroidal structure, spheroids in collagen hydrogels formed elongated structures. These findings highlight the potential use of uniluminal vascular spheroids as modules to engineer blood vessels. We also demonstrate that uniluminal vascular spheroid fusion conforms to models describing the coalescence of liquid drops. Furthermore, the fusion of uniluminal vascular spheroids in vitro closely resembled the in vivo process by which the descending aorta forms from the fusion of the paired dorsal aortae during embryonic development. Together, the findings indicate that tissue liquidity underlies uniluminal vascular spheroid fusion and that in vivo anastomosis of blood vessels may involve a similar mechanism. PMID:19918756

Vascular surgery is an unattractive career option for current basic surgical trainees: a regional perspective.

PubMed

Currie, S; Coughlin, P A; Bhasker, S; Hossain, J; Irvine, C D; Curley, P J

2007-11-01

The workload of vascular services will substantially increase in the foreseeable future with the recent changes in surgical training presenting a challenge to training and recruitment in vascular surgery. This study aimed to determine the current feelings towards vascular surgery as a career choice from basic surgical trainees (BSTs) within a single region. BSTs from a single region were questioned. Probable career specialty choice was ascertained, as were suggestions for changes to the career pathway of a vascular surgeon to make it a more attractive career choice. Seventy-seven of 110 BSTs returned the questionnaire. Of the 77, 52 had previous experience of a vascular firm. Ten BSTs had been on a pure vascular firm as an SHO and 52 had been on a general surgical firm. No BST specified vascular surgery as their ultimate career choice. Career choices included general surgery (n = 30), orthopaedics (n = 17), plastic surgery (n = 9) and urology (n = 5). Thirty-three BSTs would not be tempted at all to a career in vascular surgery. Changes in the career structure that would result in BSTs contemplating a career in vascular surgery included the inclusion of endovascular surgery (n = 13), no compulsion to undertake a period of research (n = 5), pure vascular training (n = 2), more general surgical training (n = 2) and less onerous on-calls when older (n = 2). The lack of trainees wishing to become vascular surgeons is of grave concern. Increasing the endovascular capabilities of vascular surgeons as well as altering the stance on research may have an increasingly positive role in recruitment.

Roll, Spin, Wash, or Filter? Processing of Lipoaspirate for Autologous Fat Grafting: An Updated, Evidence-Based Review of the Literature.

PubMed

Cleveland, Emily C; Albano, Nicholas J; Hazen, Alexes

2015-10-01

The use of autologous adipose tissue harvested through liposuction techniques for soft-tissue augmentation has become commonplace among cosmetic and reconstructive surgeons alike. Despite its longstanding use in the plastic surgery community, substantial controversy remains regarding the optimal method of processing harvested lipoaspirate before grafting. This evidence-based review builds on prior examinations of the literature to evaluate both established and novel methods for lipoaspirate processing. A comprehensive, systematic review of the literature was conducted using Ovid MEDLINE in January of 2015 to identify all relevant publications subsequent to the most recent review on this topic. Randomized controlled trials, clinical trials, and comparative studies comparing at least two of the following techniques were included: decanting, cotton gauze (Telfa) rolling, centrifugation, washing, filtration, and stromal vascular fraction isolation. Nine articles comparing various methods of processing human fat for autologous grafting were selected based on inclusion and exclusion criteria. Five compared established processing techniques (i.e., decanting, cotton gauze rolling, centrifugation, and washing) and four publications evaluated newer proprietary technologies, including washing, filtration, and/or methods to isolate stromal vascular fraction. The authors failed to find compelling evidence to advocate a single technique as the superior method for processing lipoaspirate in preparation for autologous fat grafting. A paucity of high-quality data continues to limit the clinician's ability to determine the optimal method for purifying harvested adipose tissue. Novel automated technologies hold promise, particularly for large-volume fat grafting; however, extensive additional research is required to understand their true utility and efficiency in clinical settings.

Use of the national surgical quality improvement program to reduce surgical mortality: implementation of intensive preoperative screening and intervention.

PubMed

Konstantinidis, Agathoklis; Fogel, Sandy; Jones, James; Gilliam, Brenda; Kundzins, John; Baker, Christopher

2014-09-01

The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data at our institution indicated that surgical mortality was significantly higher than expected. This study examines the effect of implementation of a strict, intensive preoperative screening and intervention process on postoperative mortality at our institution, as measured by the NSQIP. Carilion Roanoke Memorial Hospital (CRMH) is a 763-bed tertiary care hospital serving a population of one million people in southwest Virginia. Data were collected for NSQIP at CRMH from July 2007 to December 2012. In January 2010, a new preoperative process was implemented to include risk assessment and intervention for hypertension, cardiac disease, pulmonary disease, diabetes, renal disease, and obstructive sleep apnea. Before initiation of our preoperative program (July 2007 to January 2010), odds ratios (ORs) for 30-day mortality in general and vascular cases were significantly higher than expected (1.40, 1.43, 1.58, and 1.56 in successive reporting periods). Beginning with the first report after implementation of the preoperative screening program, CRMH showed a progressively decreasing OR for overall 30-day mortality (1.26, 1.19, 1.14, 0.86, 0.82, 0.84, 0.89) with similar reductions in both general (0.92) and vascular (0.92) surgery. The implementation of an intensive preoperative screening and intervention process in our institution was accompanied by a significant decrease in the 30-day mortality for general surgery and vascular procedures, as measured by the NSQIP.

Modelling the development and arrangement of the primary vascular structure in plants.

PubMed

Cartenì, Fabrizio; Giannino, Francesco; Schweingruber, Fritz Hans; Mazzoleni, Stefano

2014-09-01

The process of vascular development in plants results in the formation of a specific array of bundles that run throughout the plant in a characteristic spatial arrangement. Although much is known about the genes involved in the specification of procambium, phloem and xylem, the dynamic processes and interactions that define the development of the radial arrangement of such tissues remain elusive. This study presents a spatially explicit reaction-diffusion model defining a set of logical and functional rules to simulate the differentiation of procambium, phloem and xylem and their spatial patterns, starting from a homogeneous group of undifferentiated cells. Simulation results showed that the model is capable of reproducing most vascular patterns observed in plants, from primitive and simple structures made up of a single strand of vascular bundles (protostele), to more complex and evolved structures, with separated vascular bundles arranged in an ordered pattern within the plant section (e.g. eustele). The results presented demonstrate, as a proof of concept, that a common genetic-molecular machinery can be the basis of different spatial patterns of plant vascular development. Moreover, the model has the potential to become a useful tool to test different hypotheses of genetic and molecular interactions involved in the specification of vascular tissues.

Multimodal Retinal Imaging in Incontinentia Pigmenti Including Optical Coherence Tomography Angiography: Findings From an Older Cohort With Mild Phenotype.

PubMed

Liu, Tin Yan Alvin; Han, Ian C; Goldberg, Morton F; Linz, Marguerite O; Chen, Connie J; Scott, Adrienne W

2018-05-01

Incontinentia pigmenti (IP) is a rare, X-linked dominant disease with potentially severe ocular complications that predominantly affect the peripheral retina. However, little is known about its effects on the macula. To describe the structural and vascular abnormalities observed in the maculas of patients with IP and to correlate these findings with peripheral pathologies. Prospective, cross-sectional study at Wilmer Eye Institute, Johns Hopkins University. Five participants with a clinical diagnosis of IP were included and underwent multimodal imaging with ultra-wide-field fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), and OCT angiography. The structural and vascular abnormalities observed on spectral-domain OCT and OCT angiography and their correlation with peripheral pathologies seen on ultra-wide-field FA. A total of 9 eyes from 5 patients (median age, 20.5 years; range, 8.4-54.2 years) were included. Median Snellen visual acuity was 20/32 (range, 20/16 to 20/63). ultra-wide-field FA-identified retinal vascular abnormalities in all 7 eyes in which FA was obtained. These abnormalities included microaneurysms, areas of nonperfusion, and vascular anastomoses, most of which were peripheral to the standard view of 30° FA with peripheral sweeps. Structural abnormalities were observed in 6 eyes on spectral-domain OCT, including inner retinal thinning and irregularities in the outer plexiform layer. Optical coherence tomography angiography abnormalities were noted in all 9 eyes, including decreased vascular density, abnormal vascular loops, and flow loss in the superficial and deep plexuses, which corresponded to areas of retinal thinning on spectral-domain OCT. Although our study is limited by the small sample size, the findings suggest that multimodal imaging is useful for detecting structural and vascular abnormalities that may not be apparent on ophthalmoscopy in patients with IP. Macular pathologies, especially a decrease in vascular density on OCT angiography, are common. Further studies are needed to characterize further the association between macular and peripheral abnormalities in patients with IP.

Shear-induced endothelial mechanotransduction: the interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications

PubMed Central

2014-01-01

Hemodynamic shear stress, the blood flow-generated frictional force acting on the vascular endothelial cells, is essential for endothelial homeostasis under normal physiological conditions. Mechanosensors on endothelial cells detect shear stress and transduce it into biochemical signals to trigger vascular adaptive responses. Among the various shear-induced signaling molecules, reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in vascular homeostasis and diseases. In this review, we explore the molecular, cellular, and vascular processes arising from shear-induced signaling (mechanotransduction) with emphasis on the roles of ROS and NO, and also discuss the mechanisms that may lead to excessive vascular remodeling and thus drive pathobiologic processes responsible for atherosclerosis. Current evidence suggests that NADPH oxidase is one of main cellular sources of ROS generation in endothelial cells under flow condition. Flow patterns and magnitude of shear determine the amount of ROS produced by endothelial cells, usually an irregular flow pattern (disturbed or oscillatory) producing higher levels of ROS than a regular flow pattern (steady or pulsatile). ROS production is closely linked to NO generation and elevated levels of ROS lead to low NO bioavailability, as is often observed in endothelial cells exposed to irregular flow. The low NO bioavailability is partly caused by the reaction of ROS with NO to form peroxynitrite, a key molecule which may initiate many pro-atherogenic events. This differential production of ROS and RNS (reactive nitrogen species) under various flow patterns and conditions modulates endothelial gene expression and thus results in differential vascular responses. Moreover, ROS/RNS are able to promote specific post-translational modifications in regulatory proteins (including S-glutathionylation, S-nitrosylation and tyrosine nitration), which constitute chemical signals that are relevant in cardiovascular pathophysiology. Overall, the dynamic interplay between local hemodynamic milieu and the resulting oxidative and S-nitrosative modification of regulatory proteins is important for ensuing vascular homeostasis. Based on available evidence, it is proposed that a regular flow pattern produces lower levels of ROS and higher NO bioavailability, creating an anti-atherogenic environment. On the other hand, an irregular flow pattern results in higher levels of ROS and yet lower NO bioavailability, thus triggering pro-atherogenic effects. PMID:24410814

Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation.

PubMed

Bressan, Michael; Davis, Patricia; Timmer, John; Herzlinger, Doris; Mikawa, Takashi

2009-02-01

Embryonic blood vessel formation is initially mediated through the sequential differentiation, migration, and assembly of endothelial cells (ECs). While many molecular signals that promote vascular development have been identified, little is known about suppressors of this process. In higher vertebrates, including birds and mammals, the vascular network forms throughout the embryonic disk with the exception of a region along the midline. We have previously shown that the notochord is responsible for the generation and maintenance of the avascular midline and that BMP antagonists expressed by this embryonic tissue, including Noggin and Chordin, can mimic this inhibitory role. Here we report that the notochord suppresses the generation of ECs from the mesoderm both in vivo and in vitro. We also report that the notochord diminishes the ability of mature ECs to organize into a primitive plexus. Furthermore, Noggin mimics notochord-based inhibition by preventing mesodermal EC generation and mature EC network formation. These findings suggest that the mesoderm surrounding the midline is competent to give rise to ECs and to form blood vessels, but that notochord derived-BMP antagonists suppress EC differentiation and maturation processes leading to inhibition of midline vessel formation.

Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

PubMed

Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

2016-06-01

Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

Vascular plugs - A key companion to Interventionists - 'Just Plug it'.

PubMed

Ramakrishnan, Sivasubramanian

2015-01-01

Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory. Copyright © 2015. Published by Elsevier B.V.

Management of Major Vascular Injury During Endoscopic Endonasal Skull Base Surgery.

PubMed

Gardner, Paul A; Snyderman, Carl H; Fernandez-Miranda, Juan C; Jankowitz, Brian T

2016-06-01

A major vascular injury is the most feared complication of endoscopic sinus and skull base surgery. Risk factors for vascular injury are discussed, and an algorithm for management of a major vascular injury is presented. A team of surgeons (otolaryngology and neurosurgery) is important for identification and control of a major vascular injury applying basic principles of vascular control. A variety of techniques can be used to control a major injury, including coagulation, a muscle patch, sacrifice of the artery, and angiographic stenting. Immediate and close angiographic follow-up is critical to prevent and manage subsequent complications of vascular injury. Copyright © 2016 Elsevier Inc. All rights reserved.

[Malignant vascular tumors of the vulva].

PubMed

Chokoeva, A; Tchernev, G

2015-01-01

Due to the increased vascularity as well as the unique anatomical structure, vascular lesions, which occur in the female reproductive system are common observed and diverse by their morphology. The majority of them are benign, including vascular malformations, lesions due to vascular hyperplasia, tumors with significant vascular component and others. Malignant vascular tumors are rare in the area of the vulva accounting about 1% of all vulvar lesions with vascular origin. Kaposi sarcoma, epithelioid hemangioepithelioma and epithelioid angiosarcoma have been reported with vulvar localization. With a view to their rare incidence, nonspecific clinical manifestation and aggressive behavior associated with high mortality, we present the most common malignant tumors of vascular origin arising in the vulva, as we emphasize on their epidemiology and clinical features, differential diagnosis and therapeutic algorithms for this rare type of malignancies.

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.

Boron and Poloxamer (F68 and F127) Containing Hydrogel Formulation for Burn Wound Healing.

PubMed

Demirci, Selami; Doğan, Ayşegül; Karakuş, Emre; Halıcı, Zekai; Topçu, Atila; Demirci, Elif; Sahin, Fikrettin

2015-11-01

Burn injuries, the most common and destructive forms of wounds, are generally accompanied with life-threatening infections, inflammation, reduced angiogenesis, inadequate extracellular matrix production, and lack of growth factor stimulation. In the current study, a new antimicrobial carbopol-based hydrogel formulated with boron and pluronic block copolymers was evaluated for its healing activity using in vitro cell culture techniques and an experimental burn model. Cell viability, gene expression, and wound healing assays showed that gel formulation increased wound healing potential. In vitro tube-like structure formation and histopathological examinations revealed that gel not only increased wound closure by fibroblastic cell activity, but also induced vascularization process. Moreover, gel formulation exerted remarkable antimicrobial effects against bacteria, yeast, and fungi. Migration, angiogenesis, and contraction-related protein expressions including collagen, α-smooth muscle actin, transforming growth factor-β1, vimentin, and vascular endothelial growth factor were considerably enhanced in gel-treated groups. Macrophage-specific antigen showed an oscillating expression at the burn wounds, indicating the role of initial macrophage migration to the wound site and reduced inflammation phase. This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively. The formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.

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

Consensus recommendations for essential vascular care in low- and middle-income countries

PubMed Central

Stewart, Barclay T; Gyedu, Adam; Giannou, Christos; Mishra, Brijesh; Rich, Norman; Wren, Sherry; Mock, Charles; Kushner, Adam L

2016-01-01

Introduction Many low- and middle-income countries (LMICs) are ill equipped to care for the large and growing burden of vascular conditions. We aimed to develop essential vascular care recommendations that would be feasible for implementation at nearly every setting worldwide, regardless of national income. Methods The normative Delphi method was used to achieve consensus on essential vascular care resources among 27 experts in multiple areas of vascular care and public health, as well as with experience in LMIC healthcare. Five anonymous, iterative rounds of survey with controlled feedback and a statistical response were used to reach consensus on essential vascular care resources. Results The matrices provide recommendations for 92 vascular care resources at each of the four levels of care in most LMICs (i.e. primary health centers, and first-level, referral, and tertiary hospitals). The recommendations include both essential and desirable resources and encompass the following categories: screening, counseling, and evaluation; diagnostics; medical care; surgical care; equipment and supplies; and medications. Conclusion The resources recommended have the potential to improve LMIC healthcare systems’ ability to respond to the large and growing burden of vascular conditions. Many of these resources can be provided with thoughtful planning and organization without significant increases in cost. However, the resources must be incorporated into a framework that includes surveillance of vascular conditions, monitoring and evaluation of vascular capacity and care, a well functioning pre- and inter-hospital transport system, and vascular training for both existing and future healthcare providers. PMID:27432199

Consensus recommendations for essential vascular care in low- and middle-income countries.

PubMed

Stewart, Barclay T; Gyedu, Adam; Giannou, Christos; Mishra, Brijesh; Rich, Norman; Wren, Sherry M; Mock, Charles; Kushner, Adam L

2016-12-01

Many low- and middle-income countries (LMICs) are ill equipped to care for the large and growing burden of vascular conditions. We aimed to develop essential vascular care recommendations that would be feasible for implementation at nearly every setting worldwide, regardless of national income. The normative Delphi method was used to achieve consensus on essential vascular care resources among 27 experts in multiple areas of vascular care and public health as well as with experience in LMIC health care. Five anonymous, iterative rounds of survey with controlled feedback and a statistical response were used to reach consensus on essential vascular care resources. The matrices provide recommendations for 92 vascular care resources at each of the four levels of care in most LMICs, comprising primary health centers and first-level, referral, and tertiary hospitals. The recommendations include essential and desirable resources and encompass the following categories: screening, counseling, and evaluation; diagnostics; medical care; surgical care; equipment and supplies; and medications. The resources recommended have the potential to improve the ability of LMIC health care systems to respond to the large and growing burden of vascular conditions. Many of these resources can be provided with thoughtful planning and organization, without significant increases in cost. However, the resources must be incorporated into a framework that includes surveillance of vascular conditions, monitoring and evaluation of vascular capacity and care, a well functioning prehospital and interhospital transport system, and vascular training for existing and future health care providers. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Photonic Monitoring in Real-time of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Gene Expression Under Relaxin-induced Conditions in a Novel Murine Wound Model

USDA-ARS?s Scientific Manuscript database

Relaxin is known to promote vascular endotheilial growth factor (VEGF) expression in reproductive tissue and successful wound-healing is dependent upon good vascularization of wound sites, a process that relaxin may facilitate. Thus, the objective of this study was to evaluate the efficacy of relaxi...

Microcomputed Tomography Characterization of Neovascularization in Bone Tissue Engineering Applications

PubMed Central

Young, Simon; Kretlow, James D.; Nguyen, Charles; Bashoura, Alex G.; Baggett, L. Scott; Jansen, John A.; Wong, Mark

2008-01-01

Abstract Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs. PMID:18657028

Breast tumor angiogenesis analysis using 3D power Doppler ultrasound

NASA Astrophysics Data System (ADS)

Chang, Ruey-Feng; Huang, Sheng-Fang; Lee, Yu-Hau; Chen, Dar-Ren; Moon, Woo Kyung

2006-03-01

Angiogenesis is the process that correlates to tumor growth, invasion, and metastasis. Breast cancer angiogenesis has been the most extensively studied and now serves as a paradigm for understanding the biology of angiogenesis and its effects on tumor outcome and patient prognosis. Most studies on characterization of angiogenesis focus on pixel/voxel counts more than morphological analysis. Nevertheless, in cancer, the blood flow is greatly affected by the morphological changes, such as the number of vessels, branching pattern, length, and diameter. This paper presents a computer-aided diagnostic (CAD) system that can quantify vascular morphology using 3-D power Doppler ultrasound (US) on breast tumors. We propose a scheme to extract the morphological information from angiography and to relate them to tumor diagnosis outcome. At first, a 3-D thinning algorithm helps narrow down the vessels into their skeletons. The measurements of vascular morphology significantly rely on the traversing of the vascular trees produced from skeletons. Our study of 3-D assessment of vascular morphological features regards vessel count, length, bifurcation, and diameter of vessels. Investigations into 221 solid breast tumors including 110 benign and 111 malignant cases, the p values using the Student's t-test for all features are less than 0.05 indicating that the proposed features are deemed statistically significant. Our scheme focuses on the vascular architecture without involving the technique of tumor segmentation. The results show that the proposed method is feasible, and have a good agreement with the diagnosis of the pathologists.

The expression dynamics of mechanosensitive genes in extra-embryonic vasculature after heart starts to beat in chick embryo.

PubMed

Rajendran, Saranya; Sundaresan, Lakshmikirupa; Rajendran, Krithika; Selvaraj, Monica; Gupta, Ravi; Chatterjee, Suvro

2016-02-11

Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13. Therefore, we propose a novel in vivo model to study the flow experienced by developing endothelium. Using this model, we aimed to capture the transcriptome dynamics of the pre- and post-flow conditions. RNA was isolated from extra embryonic area vasculosa (EE-AV) pooled from three chick embryos between HH10-HH13 and RNA sequencing was performed. The whole transcriptome sequencing of chick identified up-regulation of some of the previously well-known mechanosensitive genes including NFR2, HAND1, CTGF and KDR. GO analyses of the up-regulated genes revealed enrichment of several biological processes including heart development, extracellular matrix organization, cell-matrix adhesion, cell migration, blood vessel development, patterning of blood vessels, collagen fibril organization. Genes encoding for gap junctions proteins which are involved in vascular remodeling and arterial-venous differentiation, and genes involved in cell-cell adhesion, and ECM interactions were significantly up-regulated. Validation of selected genes through semi quantitative PCR was performed. The study indicates that shear stress plays a major role in development. Through appropriate validation, this platform can serve as an in vivo model to study conditions of disturbed flow in pathology as well as normal flow during development.

Informed decision-making in elective major vascular surgery: analysis of 145 surgeon-patient consultations.

PubMed

Etchells, Edward; Ferrari, Michel; Kiss, Alex; Martyn, Nikki; Zinman, Deborah; Levinson, Wendy

2011-06-01

Prior studies show significant gaps in the informed decision-making process, a central goal of surgical care. These studies have been limited by their focus on low-risk decisions, single visits rather than entire consultations, or both. Our objectives were, first, to rate informed decision-making for major elective vascular surgery based on audiotapes of actual physician-patient conversations and, second, to compare ratings of informed decision-making for first visits to ratings for multiple visits by the same patient over time. We prospectively enrolled patients for whom vascular surgical treatment was a potential option at a tertiary care outpatient vascular surgery clinic. We audio-taped all surgeon-patient conversations, including multiple visits when necessary, until a decision was made. Using an existing method, we evaluated the transcripts for elements of decision-making, including basic elements (e.g., an explanation of the clinical condition), intermediate elements (e.g., risks and benefits) and complex elements (e.g., uncertainty around the decision). We analyzed 145 surgeon-patient consultations. Overall, 45% of consultations contained complex elements, whereas 23% did not contain the basic elements of decision-making. For the 67 consultations that involved multiple visits, ratings were significantly higher when evaluating all visits (50% complex elements) compared with evaluating only the first visit (33% complex elements, p < 0.001.) We found that 45% of consultations contained complex elements, which is higher than prior studies with similar methods. Analyzing decision-making over multiple visits yielded different results than analyzing decision-making for single visits.

CT Angiography after 20 Years

PubMed Central

Rubin, Geoffrey D.; Leipsic, Jonathon; Schoepf, U. Joseph; Fleischmann, Dominik; Napel, Sandy

2015-01-01

Through a marriage of spiral computed tomography (CT) and graphical volumetric image processing, CT angiography was born 20 years ago. Fueled by a series of technical innovations in CT and image processing, over the next 5–15 years, CT angiography toppled conventional angiography, the undisputed diagnostic reference standard for vascular disease for the prior 70 years, as the preferred modality for the diagnosis and characterization of most cardiovascular abnormalities. This review recounts the evolution of CT angiography from its development and early challenges to a maturing modality that has provided unique insights into cardiovascular disease characterization and management. Selected clinical challenges, which include acute aortic syndromes, peripheral vascular disease, aortic stent-graft and transcatheter aortic valve assessment, and coronary artery disease, are presented as contrasting examples of how CT angiography is changing our approach to cardiovascular disease diagnosis and management. Finally, the recently introduced capabilities for multispectral imaging, tissue perfusion imaging, and radiation dose reduction through iterative reconstruction are explored with consideration toward the continued refinement and advancement of CT angiography. PMID:24848958

Managing peatland vegetation for drinking water treatment.

PubMed

Ritson, Jonathan P; Bell, Michael; Brazier, Richard E; Grand-Clement, Emilie; Graham, Nigel J D; Freeman, Chris; Smith, David; Templeton, Michael R; Clark, Joanna M

2016-11-18

Peatland ecosystem services include drinking water provision, flood mitigation, habitat provision and carbon sequestration. Dissolved organic carbon (DOC) removal is a key treatment process for the supply of potable water downstream from peat-dominated catchments. A transition from peat-forming Sphagnum moss to vascular plants has been observed in peatlands degraded by (a) land management, (b) atmospheric deposition and (c) climate change. Here within we show that the presence of vascular plants with higher annual above-ground biomass production leads to a seasonal addition of labile plant material into the peatland ecosystem as litter recalcitrance is lower. The net effect will be a smaller litter carbon pool due to higher rates of decomposition, and a greater seasonal pattern of DOC flux. Conventional water treatment involving coagulation-flocculation-sedimentation may be impeded by vascular plant-derived DOC. It has been shown that vascular plant-derived DOC is more difficult to remove via these methods than DOC derived from Sphagnum, whilst also being less susceptible to microbial mineralisation before reaching the treatment works. These results provide evidence that practices aimed at re-establishing Sphagnum moss on degraded peatlands could reduce costs and improve efficacy at water treatment works, offering an alternative to 'end-of-pipe' solutions through management of ecosystem service provision.

Targeted disruption of deep-lying neocortical microvessels in rat using ultrashort laser pulses

NASA Astrophysics Data System (ADS)

Nishimura, Nozomi; Schaffer, Christopher B.; Friedman, Beth; Tsai, Philbert S.; Lyden, Patrick D.; Kleinfeld, David

2004-06-01

The study of neurovascular diseases such as vascular dementia and stroke require novel models of targeted vascular disruption in the brain. We describe a model of microvascular disruption in rat neocortex that uses ultrashort laser pulses to induce localized injury to specific targeted microvessels and uses two-photon microscopy to monitor and guide the photodisruption process. In our method, a train of high-intensity, 100-fs laser pulses is tightly focused into the lumen of a blood vessel within the upper 500 μm of cortex. Photodisruption induced by these laser pulses creates injury to a single vessel located at the focus of the laser, leaving the surrounding tissue intact. This photodisruption results in three modalities of localized vascular injury. At low power, blood plasma extravasation can be induced. The vessel itself remains intact, while serum is extravasated into the intercellular space. Localized ischemia caused by an intravascular clot results when the photodisruption leads to a brief disturbance of the vascular walls that initiates an endogenous clotting cascade. The formation of a localized thrombus stops the blood flow at the location of the photodisruption. A hemorrhage, defined as a large extravasation of blood including plasma and red blood cells, results when higher laser power is used. The targeted vessel does not remain intact.

Genes associated with Type 2 Diabetes and vascular complications.

PubMed

Montesanto, Alberto; Bonfigli, Anna Rita; Crocco, Paolina; Garagnani, Paolo; De Luca, Maria; Boemi, Massimo; Marasco, Elena; Pirazzini, Chiara; Giuliani, Cristina; Franceschi, Claudio; Passarino, Giuseppe; Testa, Roberto; Olivieri, Fabiola; Rose, Giuseppina

2018-02-04

Type 2 Diabetes (T2D) is a chronic disease associated with a number of micro- and macrovascular complications that increase the morbidity and mortality of patients. The risk of diabetic complications has a strong genetic component. To this end, we sought to evaluate the association of 40 single nucleotide polymorphisms (SNPs) in 21 candidate genes with T2D and its vascular complications in 503 T2D patients and 580 healthy controls. The genes were chosen because previously reported to be associated with T2D complications and/or with the aging process. We replicated the association of T2D risk with I GF2BP rs4402960 and detected novel associations with TERT rs2735940 and rs2736098. The addition of these SNPs to a model including traditional risk factors slightly improved risk prediction. After stratification of patients according to the presence/absence of vascular complications, we found significant associations of variants in the CAT , FTO , and UCP1 genes with diabetic retinopathy and nephropathy. Additionally, a variant in the ADIPOQ gene was found associated with macrovascular complications. Notably, these genes are involved in some way in mitochondrial biology and reactive oxygen species regulation. Hence, our findings strongly suggest a potential link between mitochondrial oxidative homeostasis and individual predisposition to diabetic vascular complications.

The Vascular Microarchitecture of the Human Fetal Pancreas: A Corrosion Casting and Scanning Electron Microscopy Study.

PubMed

Gorczyca, Janusz; Tomaszewski, Krzysztof A; Henry, Brandon Michael; Pękala, Przemysław Andrzej; Pasternak, Artur; Mizia, Ewa; Walocha, Jerzy A

2017-01-01

Detailed knowledge on the development of the pancreas is required to understand the variability in its blood supply. The aim of our study was to use the corrosion casting method combined with scanning electron microscopy to study the organization of the pancreatic microcirculation in human fetuses. The study was conducted on 28 human fetuses aged 18 to 25 gestational weeks. The fetal vasculature was appropriately prepared and then perfused with a low-viscosity Mercox CL-2R resin. The prepared vascular casts of the surface of the fetal pancreas were then examined in scanning electron microscopy and digitally analyzed. The lobular structure of the pancreas has a strong impact on the organization of the microvasculature. The lobular networks were supplied by the interlobular arteries and drained by the interlobular veins. The vascular system of fetal human pancreas has many portal connections, including islet-lobule and islet-duct portal circulations, which likely play a key role in the coordination of both endocrine and exocrine pancreatic functions. The organization of the microvascular network of the human pancreas in fetuses aged 18 to 25 gestational weeks is very similar to that of an adult but with more prominent features suggesting active processes of angiogenesis and vascular remodeling.

Managing peatland vegetation for drinking water treatment

PubMed Central

Ritson, Jonathan P.; Bell, Michael; Brazier, Richard E.; Grand-Clement, Emilie; Graham, Nigel J. D.; Freeman, Chris; Smith, David; Templeton, Michael R.; Clark, Joanna M.

2016-01-01

Peatland ecosystem services include drinking water provision, flood mitigation, habitat provision and carbon sequestration. Dissolved organic carbon (DOC) removal is a key treatment process for the supply of potable water downstream from peat-dominated catchments. A transition from peat-forming Sphagnum moss to vascular plants has been observed in peatlands degraded by (a) land management, (b) atmospheric deposition and (c) climate change. Here within we show that the presence of vascular plants with higher annual above-ground biomass production leads to a seasonal addition of labile plant material into the peatland ecosystem as litter recalcitrance is lower. The net effect will be a smaller litter carbon pool due to higher rates of decomposition, and a greater seasonal pattern of DOC flux. Conventional water treatment involving coagulation-flocculation-sedimentation may be impeded by vascular plant-derived DOC. It has been shown that vascular plant-derived DOC is more difficult to remove via these methods than DOC derived from Sphagnum, whilst also being less susceptible to microbial mineralisation before reaching the treatment works. These results provide evidence that practices aimed at re-establishing Sphagnum moss on degraded peatlands could reduce costs and improve efficacy at water treatment works, offering an alternative to ‘end-of-pipe’ solutions through management of ecosystem service provision. PMID:27857210

H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects

PubMed Central

Kumar, Gaurav; Chhabra, Aastha; Mishra, Shalini; Kalam, Haroon; Kumar, Dhiraj; Meena, Ramniwas; Ahmad, Yasmin; Bhargava, Kalpana; Prasad, Dipti N.; Sharma, Manish

2016-01-01

Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased ‘statistical co-expression networks’ generated utilizing temporal, differential transcriptome signatures of hippocampus—centrally involved in regulating cognition—implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment. PMID:27211559

Micromachined needles and lancets with design adjustable bevel angles

NASA Astrophysics Data System (ADS)

Sparks, Douglas; Hubbard, Timothy

2004-08-01

A new method of micromachining hollow needles and two-dimensional needle arrays from single crystal silicon is described. The process involves a combination of fusion bonding, photolithography and anisotropic plasma etching. The cannula produced with this process can have design adjustable bevel angles, wall thickness and channel dimensions. A subset of processing steps can be employed to produce silicon blades and lancets with design adjustable bevel angles and shaft dimensions. Applications for this technology include painless drug infusion, blood diagnosis, glucose monitoring, cellular injection and the manufacture of microkeratomes for ocular, vascular and neural microsurgery.

Increased Serum Alkaline Phosphatase and Serum Phosphate as Predictors of Mortality after Stroke

PubMed Central

S, Pratibha; JB, Agadi

2014-01-01

Context: Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. Aims: To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Materials and Methods: Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Results: Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged. PMID:25300293

Increased serum alkaline phosphatase and serum phosphate as predictors of mortality after stroke.

PubMed

S, Pratibha; S, Praveen-Kumar; Jb, Agadi

2014-08-01

Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged.

A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability

PubMed Central

2014-01-01

Background Numerous inflammation-related pathways have been shown to play important roles in atherogenesis. Rapid and efficient assessment of the relative influence of each of those pathways is a challenge in the era of “omics” data generation. The aim of the present work was to develop a network model of inflammation-related molecular pathways underlying vascular disease to assess the degree of translatability of preclinical molecular data to the human clinical setting. Methods We constructed and evaluated the Vascular Inflammatory Processes Network (V-IPN), a model representing a collection of vascular processes modulated by inflammatory stimuli that lead to the development of atherosclerosis. Results Utilizing the V-IPN as a platform for biological discovery, we have identified key vascular processes and mechanisms captured by gene expression profiling data from four independent datasets from human endothelial cells (ECs) and human and murine intact vessels. Primary ECs in culture from multiple donors revealed a richer mapping of mechanisms identified by the V-IPN compared to an immortalized EC line. Furthermore, an evaluation of gene expression datasets from aortas of old ApoE-/- mice (78 weeks) and human coronary arteries with advanced atherosclerotic lesions identified significant commonalities in the two species, as well as several mechanisms specific to human arteries that are consistent with the development of unstable atherosclerotic plaques. Conclusions We have generated a new biological network model of atherogenic processes that demonstrates the power of network analysis to advance integrative, systems biology-based knowledge of cross-species translatability, plaque development and potential mechanisms leading to plaque instability. PMID:24965703

Physiological and Therapeutic Vascular Remodeling Mediated by Hypoxia-Inducible Factor 1

NASA Astrophysics Data System (ADS)

Sarkar, Kakali; Semenza, Gregg L.

Angiogenesis along with arteriogenesis and vasculogenesis is a fundamental process in ischemic repair in adult animals including humans. Hypoxia-inducible factor 1 (HIF-1) plays a central role in mediating adaptive responses to hypoxia/ischemia by expressing angiogenic cytokines/growth factors and their cognate receptors. Angiogenic growth factors are the homing signal for circulating angiogenic cells (CACs), which are mobilized to peripheral blood from bone marrow, recruited to target tissues, and promote vascularization. Impairment of HIF-1-mediated gene transcription contributes to the impaired vascular responses in peripheral vascular disease that are associated with aging and diabetes. Promoting neovascularization in ischemic tissues is a promising strategy for the treatment of peripheral vascular disease when surgical or catheter-based revascularization is not possible. Intramuscular injection of an adenovirus encoding a constitutively active form of HIF-1α (AdCA5), into the ischemic limb of diabetic mice increases the recovery of limb perfusion and function, rescues the diabetes-associated impairment of CACs, and increases vascularization. Administration of AdCA5 overcomes the effect of aging on recovery of blood flow in middle-aged mice following femoral artery ligation in a mouse model of age-dependent critical limb ischemia. Intramuscular injection of AdCA5 along with intravenous injection of bone-marrow-derived angiogenic cells cultured in the presence of prolyl-4-hydroxylase inhibitor dimethyloxalylglycine, increases blood flow and limb salvage in old mice following femoral artery ligation. HIF-1α gene therapy increases homing of bone-marrow-derived cells, whereas induction of HIF-1 in these cells increases their retention in the ischemic tissue by increasing their adhesion to endothelium leading to synergistic effects of combined therapy on improving blood flow.

Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein.

PubMed

Kumar, Devender; Ristow, Laura C; Shi, Meiqing; Mukherjee, Priyanka; Caine, Jennifer A; Lee, Woo-Yong; Kubes, Paul; Coburn, Jenifer; Chaconas, George

2015-12-01

Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d-/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration.

Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein

PubMed Central

Kumar, Devender; Ristow, Laura C.; Shi, Meiqing; Mukherjee, Priyanka; Caine, Jennifer A.; Lee, Woo-Yong; Kubes, Paul; Coburn, Jenifer; Chaconas, George

2015-01-01

Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d -/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration. PMID:26684456

Plasma treatment effect on angiogenesis in wound healing process evaluated in vivo using angiographic optical coherence tomography

NASA Astrophysics Data System (ADS)

Kim, D. W.; Park, T. J.; Jang, S. J.; You, S. J.; Oh, W. Y.

2016-12-01

Non-thermal atmospheric pressure plasma holds promise for promoting wound healing. However, plasma-induced angiogenesis, which is important to better understand the underlying physics of plasma treatment effect on wound healing, remains largely unknown. We therefore evaluated the effect of non-thermal plasma on angiogenesis during wound healing through longitudinal monitoring over 30 days using non-invasive angiographic optical coherence tomography imaging in vivo. We demonstrate that the plasma-treated vascular wound area of mouse ear was noticeably decreased as compared to that of control during the early days in the wound healing process. We also observed that the vascular area density was increased in the plasma affected region near the wound as compared to the plasma unaffected region. The difference in the vascular wound area and the vascular area density peaked around day 3. This indicates that the plasma treatment induced additional angiogenic effects in the wound healing process especially during the early days. This non-invasive optical angiographic approach for in vivo time-lapse imaging provides further insights into elucidating plasma-induced angiogenesis in the wound healing process and its application in the biomedical plasma evaluation.

Interventional MR: vascular applications.

PubMed

Smits, H F; Bos, C; van der Weide, R; Bakker, C J

1999-01-01

Three strategies for visualisation of MR-dedicated guidewires and catheters have been proposed, namely active tracking, the technique of locally induced field inhomogeneity and passive susceptibility-based tracking. In this article the pros and cons of these techniques are discussed, including the development of MR-dedicated guidewires and catheters, scan techniques, post-processing tools, and display facilities for MR tracking. Finally, some of the results obtained with MR tracking are discussed.

Vascularization strategies for tissue engineers.

PubMed

Dew, Lindsey; MacNeil, Sheila; Chong, Chuh Khiun

2015-01-01

All tissue-engineered substitutes (with the exception of cornea and cartilage) require a vascular network to provide the nutrient and oxygen supply needed for their survival in vivo. Unfortunately the process of vascular ingrowth into an engineered tissue can take weeks to occur naturally and during this time the tissues become starved of essential nutrients, leading to tissue death. This review initially gives a brief overview of the processes and factors involved in the formation of new vasculature. It then summarizes the different approaches that are being applied or developed to overcome the issue of slow neovascularization in a range of tissue-engineered substitutes. Some potential future strategies are then discussed.

Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

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

Gao, Fu; Chambon, Pierre; Tellides, George

Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our studymore » was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2{sup f/f}) and their corresponding wild-type background mice (MyhCre.Tgfbr2{sup WT/WT}) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.« less

Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

PubMed Central

Hoffman, Jared D.; Parikh, Ishita; Green, Stefan J.; Chlipala, George; Mohney, Robert P.; Keaton, Mignon; Bauer, Bjoern; Hartz, Anika M. S.; Lin, Ai-Ling

2017-01-01

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age) and compared those to old mice (18–20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD. PMID:28993728

Strategies in Interventional Radiology: Formation of an Interdisciplinary Center of Vascular Anomalies - Chances and Challenges for Effective and Efficient Patient Management.

PubMed

Sadick, Maliha; Dally, Franz Josef; Schönberg, Stefan O; Stroszczynski, Christian; Wohlgemuth, Walter A

2017-10-01

Background  Radiology is an interdisciplinary field dedicated to the diagnosis and treatment of numerous diseases and is involved in the development of multimodal treatment concepts. Method  Interdisciplinary case management, a broad spectrum of diagnostic imaging facilities and dedicated endovascular radiological treatment options are valuable tools that allow radiology to set up an interdisciplinary center for vascular anomalies. Results  Image-based diagnosis combined with endovascular treatment options is an essential tool for the treatment of patients with highly complex vascular diseases. These vascular anomalies can affect numerous parts of the body so that a multidisciplinary treatment approach is required for optimal patient care. Conclusion  This paper discusses the possibilities and challenges regarding effective and efficient patient management in connection with the formation of an interdisciplinary center for vascular anomalies with strengthening of the clinical role of radiologists. Key points   · Vascular anomalies, which include vascular tumors and malformations, are complex to diagnose and treat.. · There are far more patients with vascular anomalies requiring therapy than interdisciplinary centers for vascular anomalies - there is currently a shortage of dedicated interdisciplinary centers for vascular anomalies in Germany that can provide dedicated care for affected patients.. · Radiology includes a broad spectrum of diagnostic and minimally invasive therapeutic tools which allow the formation of an interdisciplinary center for vascular anomalies for effective, efficient and comprehensive patient management.. Citation Format · Sadick M, Dally FJ, Schönberg SO et al. Strategies in Interventional Radiology: Formation of an Interdisciplinary Center of Vascular Anomalies - Chances and Challenges for Effective and Efficient Patient Management. Fortschr Röntgenstr 2017; 189: 957 - 966. © Georg Thieme Verlag KG Stuttgart · New York.

The 2006 William Feinberg lecture: shifting the paradigm from stroke to global vascular risk estimation.

PubMed

Sacco, Ralph L

2007-06-01

By the year 2010, it is estimated that 18.1 million people worldwide will die annually because of cardiovascular diseases and stroke. "Global vascular risk" more broadly includes the multiple overlapping disease silos of stroke, myocardial infarction, peripheral arterial disease, and vascular death. Estimation of global vascular risk requires consideration of a variety of variables including demographics, environmental behaviors, and risk factors. Data from multiple studies suggest continuous linear relationships between the physiological vascular risk modulators of blood pressure, lipids, and blood glucose rather than treating these conditions as categorical risk factors. Constellations of risk factors may be more relevant than individual categorical components. Exciting work with novel risk factors may also have predictive value in estimates of global vascular risk. Advances in imaging have led to the measurement of subclinical conditions such as carotid intima-media thickness and subclinical brain conditions such as white matter hyperintensities and silent infarcts. These subclinical measurements may be intermediate stages in the transition from asymptomatic to symptomatic vascular events, appear to be associated with the fundamental vascular risk factors, and represent opportunities to more precisely quantitate disease progression. The expansion of studies in molecular epidemiology and detection of genetic markers underlying vascular risks also promises to extend our precision of global vascular risk estimation. Global vascular risk estimation will require quantitative methods that bundle these multi-dimensional data into more precise estimates of future risk. The power of genetic information coupled with data on demographics, risk-inducing behaviors, vascular risk modulators, biomarkers, and measures of subclinical conditions should provide the most realistic approximation of an individual's future global vascular risk. The ultimate public health benefit, however, will depend on not only identification of global vascular risk but also the realization that we can modify this risk and prove the prediction models wrong.

Tetrahydrobiopterin in Cardiovascular Health and Disease

PubMed Central

Bendall, Jennifer K.; Douglas, Gillian; McNeill, Eileen; Channon, Keith M.

2014-01-01

Abstract Tetrahydrobiopterin (BH4) functions as a cofactor for several important enzyme systems, and considerable evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of cardiovascular health and disease. BH4 bioavailability is determined by a balance of enzymatic de novo synthesis and recycling, versus degradation in the setting of oxidative stress. Augmenting vascular BH4 levels by pharmacological supplementation has been shown in experimental studies to enhance NO bioavailability. However, it has become more apparent that the role of BH4 in other enzymatic pathways, including other NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on important aspects of vascular homeostasis, inflammation, and cardiac function. This article reviews the role of BH4 in cardiovascular development and homeostasis, as well as in pathophysiological processes such as endothelial and vascular dysfunction, atherosclerosis, inflammation, and cardiac hypertrophy. We discuss the therapeutic potential of BH4 in cardiovascular disease states and attempt to address how this modulator of intracellular NO-redox balance may ultimately provide a powerful new treatment for many cardiovascular diseases. Antioxid. Redox Signal. 20, 3040–3077. PMID:24294830

Angiogenesis in the female reproductive organs: pathological implications

PubMed Central

Reynolds, Lawrence P; Grazul-Bilska, Anna T; Redmer, Dale A

2002-01-01

The female reproductive organs (ovary, uterus, and placenta) are some of the few adult tissues that exhibit regular intervals of rapid growth. They also are highly vascular and have high rates of blood flow. Angiogenesis, or vascular growth, is therefore an important component of the growth and function of these tissues. As with many other tissues, vascular endothelial growth factors (VEGFs) and fibroblast growth factors (FGFs) appear to be major angiogenic factors in the female reproductive organs. A variety of pathologies of the female reproductive organs are associated with disturbances of the angiogenic process, including dysfunctional uterine bleeding, endometrial hyperplasia and carcinoma, endometriosis, failed implantation and subnormal foetal growth, myometrial fibroids (uterine leiomyomas) and adenomyosis, ovarian hyperstimulation syndrome, ovarian carcinoma, and polycystic ovary syndrome. These pathologies are also associated with altered expression of VEGFs and/or FGFs. In the near future, angiogenic or antiangiogenic compounds may prove to be effective therapeutic agents for treating these pathologies. In addition, monitoring of angiogenesis or angiogenic factor expression may provide a means of assessing the efficacy of these therapies. PMID:12485460

Vascular biology: cellular and molecular profiling.

PubMed

Baird, Alison E; Wright, Violet L

2006-02-01

Our understanding of the mechanisms underlying cerebrovascular atherosclerosis has improved in recent years, but significant gaps remain. New insights into the vascular biological processes that result in ischemic stroke may come from cellular and molecular profiling studies of the peripheral blood. In recent cellular profiling studies, increased levels of a proinflammatory T-cell subset (CD4 (+)CD28 (-)) have been associated with stroke recurrence and death. Expansion of this T-cell subset may occur after ischemic stroke and be a pathogenic mechanism leading to recurrent stroke and death. Increases in certain phenotypes of endothelial cell microparticles have been found in stroke patients relative to controls, possibly indicating a state of increased vascular risk. Molecular profiling approaches include gene expression profiling and proteomic methods that permit large-scale analyses of the transcriptome and the proteome, respectively. Ultimately panels of genes and proteins may be identified that are predictive of stroke risk. Cellular and molecular profiling studies of the peripheral blood and of atherosclerotic plaques may also pave the way for the development of therapeutic agents for primary and secondary stroke prevention.

Classification of the terminal arterial vascularization of the appendix with a view to its use in reconstructive microsurgery.

PubMed

Ouattara, Djibril; Kipré, Yvan Zunon; Broalet, Esperance; Séri, Fréjuis Gotta; Angaté, Hervé Yangni; Bi N'Guessan, Gabriel Gnanazan; Kassanyou, Salami

2007-12-01

The aim of this study was to examine the arterial vascularization of the appendix, in order to propose a classification of the different vascular types of the appendix for the realization of free transfer in reconstructive microsurgery. We achieved the removal as a monobloc of the cecum, of a part of the ileum, and the upper colon, then conducted the intra-arterial injection of a mixture composed of minium, and went on to the dissection of 25 specimens of appendix from West Africa. We analyzed the appendicular territory vascularized by the different discovered arteries. The average length of the appendix was 10.5 cm, ranging from 6.5 to 13.5 cm. The vascularization of the appendix was guaranteed by three arteries: the main appendicular artery, the ceco-appendicular artery and by one or several appendicular accessory arteries. We found five types of vascularization of the appendix according to the number and type of artery needed to guarantee the vascularization of the whole of the appendix including its base. It is evident from this study that a detailed analysis of the vascularization of the appendix is necessary before its removal for a reconstructive microsurgery, because in three cases out of four, the transplant must include at least two vessels in order to guarantee the whole of its vascularization.

Combined Dual-Task Gait Training and Aerobic Exercise to Improve Cognition, Mobility, and Vascular Health in Community-Dwelling Older Adults at Risk for Future Cognitive Decline1.

PubMed

Gregory, Michael A; Boa Sorte Silva, Narlon C; Gill, Dawn P; McGowan, Cheri L; Liu-Ambrose, Teresa; Shoemaker, J Kevin; Hachinski, Vladimir; Holmes, Jeff; Petrella, Robert J

2017-01-01

This 6-month experimental case series study investigated the effects of a dual-task gait training and aerobic exercise intervention on cognition, mobility, and cardiovascular health in community-dwelling older adults without dementia. Participants exercised 40 min/day, 3 days/week for 26 weeks on a Biodex GaitTrainer2 treadmill. Participants were assessed at baseline (V0), interim (V1: 12-weeks), intervention endpoint (V2: 26-weeks), and study endpoint (V3: 52-weeks). The study outcomes included: cognition [executive function (EF), processing speed, verbal fluency, and memory]; mobility: usual & dual-task gait (speed, step length, and stride time variability); and vascular health: ambulatory blood pressure, carotid arterial compliance, and intima-media thickness (cIMT). Fifty-six participants [age: 70(6) years; 61% female] were included in this study. Significant improvements following the exercise program (V2) were observed in cognition: EF (p = 0.002), processing speed (p < 0.001), verbal fluency [digit symbol coding (p < 0.001), phonemic verbal fluency (p < 0.001)], and memory [immediate recall (p < 0.001) and delayed recall (p < 0.001)]; mobility: usual & dual-task gait speed (p = 0.002 and p < 0.001, respectively) and step length (p = 0.001 and p = 0.003, respectively); and vascular health: cIMT (p = 0.002). No changes were seen in the remaining outcomes. In conclusion, 26 weeks of dual-task gait training and aerobic exercise improved performance on a number of cognitive outcomes, while increasing usual & dual-task gait speed and step length in a sample of older adults without dementia.

Genomic and non-genomic effects of androgens in the cardiovascular system: clinical implications

PubMed Central

Lucas-Herald, Angela K.; Alves-Lopes, Rheure; Montezano, Augusto C.; Ahmed, S. Faisal

2017-01-01

The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells. Androgens are essential for many developmental and physiological processes, especially in male reproductive tissues. It is now clear that androgens have multiple actions besides sex differentiation and sexual maturation and that many physiological systems are influenced by androgens, including regulation of cardiovascular function [nitric oxide (NO) release, Ca2+ mobilization, vascular apoptosis, hypertrophy, calcification, senescence and reactive oxygen species (ROS) generation]. This review focuses on evidence indicating that interplay between genomic and non-genomic actions of testosterone may influence cardiovascular function. PMID:28645930

Angiogenesis and microvasculature in the female reproductive organs: physiological and pathological implications.

PubMed

Shimizu, Takashi; Hoshino, Yumi; Miyazaki, Hitoshi; Sato, Eimei

2012-01-01

The female reproductive organs such as ovary, uterus, and placenta are some of the few adult tissues that exhibit regular intervals of rapid growth, and are highly vascularized and have high rates of blood flow. Angiogenesis is a process of vascular growth that is mainly limited to the reproductive system in healthy adult animals. The development of new blood vessels in the ovary and uterus is essential to guarantee the necessary supply of nutrients and hormones. The genetic and molecular mechanisms that control the development of capillary blood vessels in the reproductive organs are beginning to be elucidated. Reproductive organs contain and produce angiogenic factors which may act alone or in concert to regulate the process of vasculature. Vascular endothelial growth factors (VEGFs) and fibroblast growth factor (FGFs) are key factors for vascular system in the reproductive organs. Recent numerous studies reported several roles of VEGFs and FGFs on ovarian and uterine functions. In this review, we focus on the involvement of VEGFs and FGFs as angiogenic factors on reproductive organs and vascular therapy for diseases of reproductive organs using anti-angiogenic agents.

Optical coherence tomography angiography monitors human cutaneous wound healing over time.

PubMed

Deegan, Anthony J; Wang, Wendy; Men, Shaojie; Li, Yuandong; Song, Shaozhen; Xu, Jingjiang; Wang, Ruikang K

2018-03-01

In vivo imaging of the complex cascade of events known to be pivotal elements in the healing of cutaneous wounds is a difficult but essential task. Current techniques are highly invasive, or lack the level of vascular and structural detail required for accurate evaluation, monitoring and treatment. We aimed to use an advanced optical coherence tomography (OCT)-based angiography (OCTA) technique for the non-invasive, high resolution imaging of cutaneous wound healing. We used a clinical prototype OCTA to image, identify and track key vascular and structural adaptations known to occur throughout the healing process. Specific vascular parameters, such as diameter and density, were measured to aid our interpretations under a spatiotemporal framework. We identified multiple distinct, yet overlapping stages, hemostasis, inflammation, proliferation, and remodeling, and demonstrated the detailed vascularization and anatomical attributes underlying the multifactorial processes of dermatologic wound healing. OCTA provides an opportunity to both qualitatively and quantitatively assess the vascular response to acute cutaneous damage and in the future, may help to ascertain wound severity and possible healing outcomes; thus, enabling more effective treatment options.

Optical coherence tomography angiography monitors human cutaneous wound healing over time

PubMed Central

Deegan, Anthony J.; Wang, Wendy; Men, Shaojie; Li, Yuandong; Song, Shaozhen; Xu, Jingjiang

2018-01-01

Background In vivo imaging of the complex cascade of events known to be pivotal elements in the healing of cutaneous wounds is a difficult but essential task. Current techniques are highly invasive, or lack the level of vascular and structural detail required for accurate evaluation, monitoring and treatment. We aimed to use an advanced optical coherence tomography (OCT)-based angiography (OCTA) technique for the non-invasive, high resolution imaging of cutaneous wound healing. Methods We used a clinical prototype OCTA to image, identify and track key vascular and structural adaptations known to occur throughout the healing process. Specific vascular parameters, such as diameter and density, were measured to aid our interpretations under a spatiotemporal framework. Results We identified multiple distinct, yet overlapping stages, hemostasis, inflammation, proliferation, and remodeling, and demonstrated the detailed vascularization and anatomical attributes underlying the multifactorial processes of dermatologic wound healing. Conclusions OCTA provides an opportunity to both qualitatively and quantitatively assess the vascular response to acute cutaneous damage and in the future, may help to ascertain wound severity and possible healing outcomes; thus, enabling more effective treatment options. PMID:29675355

The Whitening of Brown Fat and Its Implications for Weight Management in Obesity.

PubMed

Shimizu, Ippei; Walsh, Kenneth

2015-06-01

Systemic inflammation resulting from dysfunction of white adipose tissue (WAT) accelerates the pathologies of diabetes and cardiovascular diseases. In contrast to WAT, brown adipose tissue (BAT) is abundant in mitochondria that produce heat by uncoupling respiratory chain process of ATP synthesis. Besides BAT's role in thermogenesis, accumulating evidence has shown that it is involved in regulating systemic metabolism. Studies have analyzed the "browning" processes of WAT as a means to combat obesity, whereas few studies have focused on the impact and molecular mechanisms that contribute to obesity-linked BAT dysfunction--a process that is associated with the "whitening" of this tissue. Compared to WAT, a dense vascular network is required to support the high energy consumption of BAT. Recently, vascular rarefaction was shown to be a significant causal factor in the whitening of BAT in mouse models. Vascular insufficiency leads to mitochondrial dysfunction and loss in BAT and contributes to systemic insulin resistance. These data suggest that BAT "whitening," resulting from vascular dysfunction, can impact obesity and obesity-linked diseases. Conversely, agents that promote BAT function could have utility in the treatment of these conditions.

[Numerical modeling of shape memory alloy vascular stent's self-expandable progress and "optimized grid" of stent].

PubMed

Xu, Qiang; Liu, Yulan; Wang, Biao; He, Jin

2008-10-01

Vascular stent is an important medical appliance for angiocardiopathy. Its key deformation process is the expandable progress of stent in the vessel. The important deformation behaviour corresponds to two mechanics targets: deformation and stress. This paper is devoted to the research and development of vascular stent with proprietary intellectual property rights. The design of NiTinol self-expandable stent is optimized by means of finite element software. ANSYS is used to build the finite element simulation model of vascular stent; the molding material is NiTinol shape memory alloy. To cope with the factors that affect the structure of stent, the shape of grid and so on, the self-expanding process of Nitinol stent is simulated through computer. By making a comparison between two kinds of stents with similar grid structure, we present a new concept of "Optimized Grid" of stent.

A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis.

PubMed

Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

2017-01-01

Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.

Optimal Surgical Therapy in a Porcine (Sus scrofa) Model of Extra-Thoracic Penetrating Trauma Resulting in Hemorrhagic Shock: ED Thoracotomy vs. Immediate Trans-Abdominal Vascular Control. A Porcine Model for Evaluating the Management of Non-Compressible Torso Hemorrhage

DTIC Science & Technology

2010-11-08

celiac aortic clamping (n=6), direct vascular control (n=6), and endovascular aortic occlusion n=6). This study presents a large animal model of class...including thoracic aortic clamping, supra- celiac aortic clamping, direct vascular control, and proximal endovascular balloon occlusion. Following vascular...subsequently underwent non-compressible hemorrhage with thoracic aortic clamping (n=6), supra- celiac aortic clamping (n=6), direct vascular control (n=6

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.

Towards organ printing: engineering an intra-organ branched vascular tree.

PubMed

Visconti, Richard P; Kasyanov, Vladimir; Gentile, Carmine; Zhang, Jing; Markwald, Roger R; Mironov, Vladimir

2010-03-01

Effective vascularization of thick three-dimensional engineered tissue constructs is a problem in tissue engineering. As in native organs, a tissue-engineered intra-organ vascular tree must be comprised of a network of hierarchically branched vascular segments. Despite this requirement, current tissue-engineering efforts are still focused predominantly on engineering either large-diameter macrovessels or microvascular networks. We present the emerging concept of organ printing or robotic additive biofabrication of an intra-organ branched vascular tree, based on the ability of vascular tissue spheroids to undergo self-assembly. The feasibility and challenges of this robotic biofabrication approach to intra-organ vascularization for tissue engineering based on organ-printing technology using self-assembling vascular tissue spheroids including clinically relevantly vascular cell sources are analyzed. It is not possible to engineer 3D thick tissue or organ constructs without effective vascularization. An effective intra-organ vascular system cannot be built by the simple connection of large-diameter vessels and microvessels. Successful engineering of functional human organs suitable for surgical implantation will require concomitant engineering of a 'built in' intra-organ branched vascular system. Organ printing enables biofabrication of human organ constructs with a 'built in' intra-organ branched vascular tree.

Vascular Cognitive Impairment in a Memory Clinic Population: Rationale and Design of the "Utrecht-Amsterdam Clinical Features and Prognosis in Vascular Cognitive Impairment" (TRACE-VCI) Study.

PubMed

Boomsma, Jooske Marije Funke; Exalto, Lieza Geertje; Barkhof, Frederik; van den Berg, Esther; de Bresser, Jeroen; Heinen, Rutger; Koek, Huiberdina Lena; Prins, Niels Daniël; Scheltens, Philip; Weinstein, Henry Chanoch; van der Flier, Wiesje Maria; Biessels, Geert Jan

2017-04-19

Vascular Cognitive Impairment (VCI) refers to cognitive dysfunction due to vascular brain injury, as a single cause or in combination with other, often neurodegenerative, etiologies. VCI is a broad construct that captures a heterogeneous patient population both in terms of cognitive and noncognitive symptoms and in terms of etiology and prognosis. This provides a challenge when applying this construct in clinical practice. This paper presents the rationale and design of the TRACE-VCI study, which investigates the clinical features and prognosis of VCI in a memory clinic setting. The TRACE-VCI project is an observational, prospective cohort study of 861 consecutive memory clinic patients with possible VCI. Between 2009 and 2013, patients were recruited through the Amsterdam Dementia Cohort of the VU University Medical Centre (VUMC) (N=665) and the outpatient memory clinic and VCI cohort of the University Medical Centre Utrecht (UMCU) (N=196). We included all patients attending the clinics with magnetic resonance imaging (MRI) evidence of vascular brain injury. Patients with a primary etiology other than vascular brain injury or neurodegeneration were excluded. Patients underwent an extensive 1-day memory clinic evaluation including an interview, physical and neurological examination, assessment of biomarkers (including those for Alzheimer-type pathologies), extensive neuropsychological testing, and an MRI scan of the brain. For prognostic analyses, the composite primary outcome measure was defined as accelerated cognitive decline (change of clinical dementia rating ≥1 or institutionalization) or (recurrent) major vascular events or death over the course of 2 years. The mean age at baseline was 67.7 (SD 8.5) years and 46.3% of patients (399/861) were female. At baseline, the median Clinical Dementia Rating was 0.5 (interquartile range [IQR] 0.5-1.0) and the median Mini-Mental State Examination score was 25 (IQR 22-28). The clinical diagnosis at baseline was dementia in 52.4% of patients (451/861), mild cognitive impairment in 24.6% (212/861), and no objective cognitive impairment in the remaining 23.0% (198/861). The TRACE-VCI study represents a large cohort of well-characterized patients with VCI in a memory clinic setting. Data processing and collection for follow-up are currently being completed. The TRACE-VCI study will provide insight into the clinical features of memory clinic patients that meet VCI criteria and establish key prognostic factors for further cognitive decline and (recurrent) major vascular events. ©Jooske Marije Funke Boomsma, Lieza Geertje Exalto, Frederik Barkhof, Esther van den Berg, Jeroen de Bresser, Rutger Heinen, Huiberdina Lena Koek, Niels Daniël Prins, Philip Scheltens, Henry Chanoch Weinstein, Wiesje Maria van der Flier, Geert Jan Biessels. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 19.04.2017.

Stem cell-derived vascular endothelial cells and their potential application in regenerative medicine

USDA-ARS?s Scientific Manuscript database

Although a 'vascular stem cell' population has not been identified or generated, vascular endothelial and mural cells (smooth muscle cells and pericytes) can be derived from currently known pluripotent stem cell sources, including human embryonic stem cells and induced pluripotent stem cells. We rev...

Involvement of the Warburg effect in non-tumor diseases processes.

PubMed

Chen, Zhe; Liu, Meiqing; Li, Lanfang; Chen, Linxi

2018-04-01

Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid β-mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non-tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non-tumor diseases. © 2017 Wiley Periodicals, Inc.

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress

PubMed Central

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-01-01

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis-induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research. PMID:29156574

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress.

PubMed

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-11-18

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis -induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research.

Revascularization procedures for Kienböck disease.

PubMed

Kakar, Sanjeev; Giuffre, Jennifer L; Shin, Alexander Y

2011-03-01

The goals of treatment in Kienböck disease include preservation of wrist function, maintaining normal wrist kinematics, and revascularization of the necrotic lunate when and if possible. A variety of pedicled vascularized bone graft options exist and include but are not limited to pedicled grafts from the volar radius, dorsal radius, metacarpal heads or bases, and pisiform. Of the various treatment options, pedicled vascularized bone grafts from the dorsal distal radius based on the fourth and fifth extensor compartment arteries has been successful in the revascularization of the necrotic lunate at our institution. Vascularized bone grafting is an attractive alternative to conventional bone grafting by improving the local biological environment and thereby promoting revascularization. Recent advances in the anatomy and physiology of vascularized pedicled bone grafts have increased our ability to apply them to the treatment of Kienböck disease. The purpose of this article is to describe the various types of pedicled vascularized bone graft available, to detail the vascular anatomy of the dorsal distal radius, and to describe the surgical technique of our preferred vascularized bone graft (the fourth+fifth extensor compartment artery graft). In addition, the indications, contraindications, and outcomes are described.

Retinal microvascular changes and subsequent vascular events after ischemic stroke.

PubMed

De Silva, D A; Manzano, J J F; Liu, E Y; Woon, F-P; Wong, W-X; Chang, H-M; Chen, C; Lindley, R I; Wang, J J; Mitchell, P; Wong, T-Y; Wong, M-C

2011-08-30

Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007. Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2-4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models. Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20-4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14-6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31-5.86) compared to those without FAN. Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors.

Integrated approaches to spatiotemporally directing angiogenesis in host and engineered tissues.

PubMed

Kant, Rajeev J; Coulombe, Kareen L K

2018-03-15

The field of tissue engineering has turned towards biomimicry to solve the problem of tissue oxygenation and nutrient/waste exchange through the development of vasculature. Induction of angiogenesis and subsequent development of a vascular bed in engineered tissues is actively being pursued through combinations of physical and chemical cues, notably through the presentation of topographies and growth factors. Presenting angiogenic signals in a spatiotemporal fashion is beginning to generate improved vascular networks, which will allow for the creation of large and dense engineered tissues. This review provides a brief background on the cells, mechanisms, and molecules driving vascular development (including angiogenesis), followed by how biomaterials and growth factors can be used to direct vessel formation and maturation. Techniques to accomplish spatiotemporal control of vascularization include incorporation or encapsulation of growth factors, topographical engineering, and 3D bioprinting. The vascularization of engineered tissues and their application in angiogenic therapy in vivo is reviewed herein with an emphasis on the most densely vascularized tissue of the human body - the heart. Vascularization is vital to wound healing and tissue regeneration, and development of hierarchical networks enables efficient nutrient transfer. In tissue engineering, vascularization is necessary to support physiologically dense engineered tissues, and thus the field seeks to induce vascular formation using biomaterials and chemical signals to provide appropriate, pro-angiogenic signals for cells. This review critically examines the materials and techniques used to generate scaffolds with spatiotemporal cues to direct vascularization in engineered and host tissues in vitro and in vivo. Assessment of the field's progress is intended to inspire vascular applications across all forms of tissue engineering with a specific focus on highlighting the nuances of cardiac tissue engineering for the greater regenerative medicine community. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Design and rationale of the AngioSeal versus the Radial approach In acute coronary SyndromE (ARISE) trial: a randomized comparison of a vascular closure device versus the radial approach to prevent vascular access site complications in non-ST-segment elevation acute coronary syndrome patients.

PubMed

de Andrade, Pedro Beraldo; E Mattos, Luiz Alberto Piva; Tebet, Marden André; Rinaldi, Fábio Salerno; Esteves, Vinícius Cardozo; Nogueira, Ederlon Ferreira; França, João Ítalo Dias; de Andrade, Mônica Vieira Athanazio; Barbosa, Robson Alves; Labrunie, André; Abizaid, Alexandre Antônio Cunha; Sousa, Amanda Guerra de Moraes Rego

2013-12-18

Arterial access is a major site of bleeding complications after invasive coronary procedures. Among strategies to decrease vascular complications, the radial approach is an established one. Vascular closure devices provide more comfort to patients and decrease hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications, requiring evidence through adequately designed randomized trials. The aim of this study is to compare the radial versus femoral approach using a vascular closure device for the incidence of arterial puncture site vascular complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy. ARISE is a national, multicenter, non-inferiority randomized clinical trial. Two hundred patients with non-ST-segment elevation acute coronary syndrome will be randomized to either radial or femoral access using a vascular closure device. The primary outcome is the occurrence of vascular complications at an arterial puncture site 30 days after the procedure, including major bleeding, retroperitoneal hematoma, compartment syndrome, hematoma ≥ 5 cm, pseudoaneurysm, arterio-venous fistula, infection, limb ischemia, arterial occlusion, adjacent nerve injury or the need for vascular surgical repair. Enrollment was initiated in September 2012, and until October 2013 91 patients were included. The inclusion phase is expected to last until the second half of 2014. The ARISE trial will help define the role of a vascular closure device as a bleeding avoidance strategy in patients with NSTEACS. ClinicalTrials.gov identifier: NCT01653587.

Radionuclide evaluation of free vascularized bone graft viability. [/sup 99m/Tc-methylene diphosphonate

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

Lisbona, R.; Rennie, W.R.J.; Daniel, R.K.

1980-02-01

Free vascularized bone grafting is a new technique applied to the reconstructive surgery of long bones affected by aggressive benign or malignant processes, as well as traumatic deficiencies. These bone lesions may be treated by en bloc excision and replacement with fibular segments or osteocutaneous flaps from the groin isolated on their vascular pedicle. Microvascular anastomosis of the pedicle at the recipient site is necessary. Radionuclide bone imaging is unique in the assessment of the free vascularized bone graft because postoperative graft uptake of radiopharmaceutical reflects patent anastomoses and segmental bone viability.

Quantifying Therapeutic and Diagnostic Efficacy in 2D Microvascular Images

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia; Vickerman, Mary B.; Keith, Patricia A.

2009-01-01

VESGEN is a newly automated, user-interactive program that maps and quantifies the effects of vascular therapeutics and regulators on microvascular form and function. VESGEN analyzes two-dimensional, black and white vascular images by measuring important vessel morphology parameters. This software guides the user through each required step of the analysis process via a concise graphical user interface (GUI). Primary applications of the VESGEN code are 2D vascular images acquired as clinical diagnostic images of the human retina and as experimental studies of the effects of vascular regulators and therapeutics on vessel remodeling.

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

Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

PubMed

Fisher, Mark

2008-01-01

Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

Setting high-impact clinical research priorities for the Society for Vascular Surgery.

PubMed

Kraiss, Larry W; Conte, Michael S; Geary, Randolph L; Kibbe, Melina; Ozaki, C Keith

2013-02-01

With the overall goal of enhancing the effectiveness and efficiency of vascular care, the Society for Vascular Surgery (SVS) recently completed a process by which it identified its top clinical research priorities to address critical gaps in knowledge guiding practitioners in prevention and treatment of vascular disease. After a survey of the SVS membership, a panel of SVS committee members and opinion leaders considered 53 distinct research questions through a structured process that resulted in identification of nine clinical issues that were felt to merit immediate attention by vascular investigators and external funding agencies. These are, in order of priority: (1) define optimal management of asymptomatic carotid stenosis, (2) compare the effectiveness of medical vs invasive treatment (open or endovascular) of vasculogenic claudication, (3) compare effectiveness of open vs endovascular infrainguinal revascularization as initial treatment of critical limb ischemia, (4) develop and compare the effectiveness of clinical strategies to reduce cardiovascular and other perioperative complications (eg, wound) after vascular intervention, (5) compare the effectiveness of strategies to enhance arteriovenous fistula maturation and durability, (6) develop best practices for management of chronic venous ulcer, (7) define optimal adjunctive medical therapy to enhance the success of lower extremity revascularization, (8) identify and evaluate medical therapy to prevent abdominal aortic aneurysm growth, and (9) evaluate ultrasound vs computed tomographic angiography surveillance after endovascular aneurysm repair. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Rivastigmine for vascular cognitive impairment.

PubMed

Birks, Jacqueline; McGuinness, Bernadette; Craig, David

2013-05-31

Vascular dementia represents the second most common type of dementia after Alzheimer's disease. In older patients, in particular, the combination of vascular dementia and Alzheimer's disease is common, and is referred to as mixed dementia. The classification of vascular dementia broadly follows three clinico-pathological processes: multi-infarct dementia, single strategic infarct dementia and subcortical dementia. Not all victims fulfil strict criteria for dementia and may be significantly cognitively impaired without memory loss, when the term vascular cognitive impairment (VCI) is more useful. Currently, no established standard treatment for VCI exists. Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer's disease and VCI, raising the possibility that cholinesterase inhibitors - such as rivastigmine - which are beneficial in Alzheimer's disease, may also be beneficial for VCI. To assess the efficacy of rivastigmine compared with placebo in the treatment of people with vascular cognitive impairment (VCI), vascular dementia or mixed dementia. We searched ALOIS (the Cochrane Dementia and Cognitive Improvement Group's Specialized Register) on 12 February 2013 using the terms: rivastigmine, exelon, "SDZ ENA 713". ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS), numerous trial registries and grey literature sources. All unconfounded randomized double-blind trials comparing rivastigmine with placebo in the treatment of people with VCI, vascular dementia or mixed dementia were eligible for inclusion. Two reviewers extracted and assessed data independently, and agreement was reached after discussion. They noted results concerning adverse effects. Three trials, with a total of 800 participants, were identified for inclusion. The participants in one trial did not have dementia, while the other two studies included participants with dementia of different severities. The dose of rivastigmine was different in each study. No pooling of study results was attempted because of these differences between the studies.One trial included 40 participants with subcortical vascular dementia (age range 40 to 90 years) with a mean mini-mental state examination (MMSE) score of 13.0 and 13.4 in the rivastigmine and placebo arms, respectively. Treatment over 26 weeks was limited to 3 mg rivastigmine twice daily, or placebo. No significant difference was found on any outcome measure relevant to cognition, neuropsychiatric symptoms, function or global rating, or in the number of withdrawals before the end of treatment.Another trial included 710 participants with vascular dementia, including subcortical and cortical forms (age range 50 to 85 years). Over 24 weeks, a mean dose of rivastigmine of 9.4 mg/day was achieved versus placebo. Baseline MMSE was identical for both groups, at 19.1. Statistically significant advantage in cognitive response (but not with global impression of change or non-cognitive measures) was seen with rivastigmine treatment at 24 weeks (MMSE change from baseline MD 0.6, 95% CI 0.11 to 1.09, P value 0.02; Vascular Dementia Assessment Scale (VaDAS) change from baseline MD -1.3, 95% CI-2.62 to 0.02, P value 0.05 ). Significantly higher rates of vomiting, nausea, diarrhoea and anorexia and withdrawals from treatment were noted in the participants randomized to rivastigmine compared with placebo (withdrawals rivastigmine 90/365, placebo 48/345, OR 2.02, 95% CI 1.38 to 2.98) (withdrawals due to an adverse event rivastigmine 49/365, placebo 19/345, OR 2.66, 95% CI 1.53 to 4.62, P value 0.0005).The third study included 50 participants (age range 48 to 84 years) with mean MMSE scores of 23.7 and 23.9 in the rivastigmine and placebo arms, respectively. Over a 24-week period, participants labelled as having cognitive impairment but no dementia (CIND) following ischaemic stroke were given up to 4.5 mg rivastigmine twice daily, or placebo. Primary and secondary outcome measures showed no statistically significant difference when considering neurocognitive abilities, function, neuropsychiatric symptoms and global performance. One participant in the rivastigmine group and two in the placebo group discontinued their medication because of an adverse effect. There is some evidence of benefit of rivastigmine in VCI from trial data from three studies. However, this conclusion is based on one large study. Rivastigmine is capable of inducing side effects that lead to withdrawal in a significant proportion of patients.

Therapeutic Angiogenesis by Gene Therapy for Critical Limb Ischemia: Choice of Biological Agent.

PubMed

Sanada, Fumihiro; Taniyama, Yoshiaki; Azuma, Junya; Yuka, Ikeda-Iwabe; Kanbara, Yasuhiro; Iwabayashi, Masaaki; Rakugi, Hiromi; Morishita, Ryuichi

2014-04-01

Peripheral artery disease (PAD) is caused by atherosclerosis, hardening and narrowing arteries over time due to buildup of fatty deposit in vascular bed called plaque. Severe blockage of an artery of the lower extremity markedly reduce blood flow, resulting in critical limb ischemia (CLI) manifested by a variety of clinical syndromes including rest pain in the feet or toes, ulcer and gangrene with infection. Despite significant advances in clinical care and interventions for revascularization, patients with CLI remain at high risk for amputation and cardiovascular death. To overcome this unmet need, therapeutic angiogenesis using angiogenic growth factors has evolved in an attempt to increase blood flow in ischemic limb. Initial animal studies and phase I clinical trials with vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF) demonstrated promising results, inspiring scientists to progress forward. However, more rigorous phase II and III clinical trials have failed to demonstrate beneficial effects of these angiogenic growth factors to date. Recently, two multicenter, double-blind, placebo-controlled clinical trials in Japan (phase III) and US (phase II) demonstrated that hepatocyte growth factor (HGF) gene therapy for CLI significant improved primary end points and tissue oxygenation up to two years in comparison to placebo. These clinical results implicate a distinct action of HGF on cellular processes involved in vascular remodeling under pathological condition. This review presents data from phase I-III clinical trials of therapeutic angiogenesis by gene therapy in patients with PAD. Further, we discuss the potential explanation for the success or failure of clinical trials in the context of the biological mechanisms underlying angiogenesis and vascular remodeling, including cellular senescence, inflammation, and tissue fibrosis.

Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option?

PubMed

Ortiz, Gustavo; Salica, Juan P; Chuluyan, Eduardo H; Gallo, Juan E

2014-11-18

Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.

Endoplasmic Reticulum Stress in Arterial Smooth Muscle Cells: A Novel Regulator of Vascular Disease

PubMed Central

Furmanik, Malgorzata; Shanahan, Catherine M.

2017-01-01

Cardiovascular disease continues to be the leading cause of death in industrialised societies. The idea that the arterial smooth muscle cell (ASMC) plays a key role in regulating many vascular pathologies has been gaining importance, as has the realisation that not enough is known about the pathological cellular mechanisms regulating ASMC function in vascular remodelling. In the past decade endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been recognised as a stress response underlying many physiological and pathological processes in various vascular cell types. Here we summarise what is known about how ER stress signalling regulates phenotypic switching, trans/dedifferentiation and apoptosis of ASMCs and contributes to atherosclerosis, hypertension, aneurysms and vascular calcification.

Improving operating room turnover time: a systems based approach.

PubMed

Bhatt, Ankeet S; Carlson, Grant W; Deckers, Peter J

2014-12-01

Operating room (OR) turnover time (TT) has a broad and significant impact on hospital administrators, providers, staff and patients. Our objective was to identify current problems in TT management and implement a consistent, reproducible process to reduce average TT and process variability. Initial observations of TT were made to document the existing process at a 511 bed, 24 OR, academic medical center. Three control groups, including one consisting of Orthopedic and Vascular Surgery, were used to limit potential confounders such as case acuity/duration and equipment needs. A redesigned process based on observed issues, focusing on a horizontally structured, systems-based approach has three major interventions: developing consistent criteria for OR readiness, utilizing parallel processing for patient and room readiness, and enhancing perioperative communication. Process redesign was implemented in Orthopedics and Vascular Surgery. Comparisons of mean and standard deviation of TT were made using an independent 2-tailed t-test. Using all surgical specialties as controls (n = 237), mean TT (hh:mm:ss) was reduced by 0:20:48 min (95 % CI, 0:10:46-0:30:50), from 0:44:23 to 0:23:25, a 46.9 % reduction. Standard deviation of TT was reduced by 0:10:32 min, from 0:16:24 to 0:05:52 and frequency of TT≥30 min was reduced from 72.5to 11.7 %. P < 0.001 for each. Using Vascular and Orthopedic surgical specialties as controls (n = 13), mean TT was reduced by 0:15:16 min (95 % CI, 0:07:18-0:23:14), from 0:38:51 to 0:23:35, a 39.4 % reduction. Standard deviation of TT reduced by 0:08:47, from 0:14:39 to 0:05:52 and frequency of TT≥30 min reduced from 69.2 to 11.7 %. P < 0.001 for each. Reductions in mean TT present major efficiency, quality improvement, and cost-reduction opportunities. An OR redesign process focusing on parallel processing and enhanced communication resulted in greater than 35 % reduction in TT. A systems-based focus should drive OR TT design.

Vascular calcification and 25-hydroxyvitamin D levels in non-dialysis patients with chronic kidney disease stages 4 and 5.

PubMed

García-Canton, Cesar; Bosch, Elvira; Ramírez, Ana; Gonzalez, Yeray; Auyanet, Ingrid; Guerra, Rita; Perez, Miguel A; Fernández, Ernesto; Toledo, Agustín; Lago, Mar; Checa, Maria D

2011-07-01

Cardiovascular disease (CVD) is the leading cause of death among chronic kidney disease (CKD) patients. Vascular calcification is highly prevalent in this population and is an independent predictor of cardiovascular mortality. Vascular calcification in uraemic patients is known to be an active and regulated process subject to the action of many promoting and inhibitory factors. The role of vitamin D in this process remains controversial. We evaluated the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) and vascular calcification evaluated by plain X-ray images, in predialysis patients with CKD stages 4 and 5. We performed a cross-sectional study with 210 CKD patients stages 4 and 5 managed at our predialysis unit. Patients were 63.5 ± 13 years of age, 60.5% males, 64.8% diabetics and 47.1% with a history of CVD. Plain X-ray images of pelvis, hands and lateral lumbar spine from all subjects were studied for calculation of semiquantitative vascular calcification scores as described by Adragao and Kauppila. We found a high prevalence of vascular calcification in our population. Adragao scores revealed only 47 patients (22.4%) without vascular calcification and 120 (57.1%) with scores higher than 3. Kauppila scores revealed only 29 patients (13.8%) without aortic calcifications and 114 patients (54.3%) with scores higher than 7. Higher vascular calcification scores were related to older age, diabetes, history of CVD and lower levels of 25(OH)D. Only 18.5% of patients had adequate levels of 25(OH)D (> 30 ng/mL), 53.7% of them had insufficient levels (15-30 ng/mL) and 27.8% had deficient levels (< 15 ng/mL). Multivariate analysis showed that age, diabetes and CVD were directly associated and 25(OH)D levels were inversely associated with vascular calcifications. Our results show an independent and negative association between serum levels of 25(OH)D and vascular calcification. Further and larger prospective studies are needed to clarify the possible role of vitamin D deficiency in the development of vascular calcification in CKD patients.

Generation of Functional Blood Vessels from a Single c-kit+ Adult Vascular Endothelial Stem Cell

PubMed Central

Fang, Shentong; Wei, Jing; Pentinmikko, Nalle; Leinonen, Hannele; Salven, Petri

2012-01-01

In adults, the growth of blood vessels, a process known as angiogenesis, is essential for organ growth and repair. In many disorders including cancer, angiogenesis becomes excessive. The cellular origin of new vascular endothelial cells (ECs) during blood vessel growth in angiogenic situations has remained unknown. Here, we provide evidence for adult vascular endothelial stem cells (VESCs) that reside in the blood vessel wall endothelium. VESCs constitute a small subpopulation within CD117+ (c-kit+) ECs capable of undergoing clonal expansion while other ECs have a very limited proliferative capacity. Isolated VESCs can produce tens of millions of endothelial daughter cells in vitro. A single transplanted c-kit-expressing VESC by the phenotype lin−CD31+CD105+Sca1+CD117+ can generate in vivo functional blood vessels that connect to host circulation. VESCs also have long-term self-renewal capacity, a defining functional property of adult stem cells. To provide functional verification on the role of c-kit in VESCs, we show that a genetic deficit in endothelial c-kit expression markedly decreases total colony-forming VESCs. In vivo, c-kit expression deficit resulted in impaired EC proliferation and angiogenesis and retardation of tumor growth. Isolated VESCs could be used in cell-based therapies for cardiovascular repair to restore tissue vascularization after ischemic events. VESCs also provide a novel cellular target to block pathological angiogenesis and cancer growth. PMID:23091420

Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases

PubMed Central

Lesslie, D P; Summy, J M; Parikh, N U; Fan, F; Trevino, J G; Sawyer, T K; Metcalf, C A; Shakespeare, W C; Hicklin, D J; Ellis, L M; Gallick, G E

2006-01-01

Vascular endothelial growth factor (VEGF) is the predominant pro-angiogenic cytokine in human malignancy, and its expression correlates with disease recurrence and poor outcomes in patients with colorectal cancer. Recently, expression of vascular endothelial growth factor receptors (VEGFRs) has been observed on tumours of epithelial origin, including those arising in the colon, but the molecular mechanisms governing potential VEGF-driven biologic functioning in these tumours are not well characterised. In this report, we investigated the role of Src family kinases (SFKs) in VEGF-mediated signalling in human colorectal carcinoma (CRC) cell lines. Vascular endothelial growth factor specifically activated SFKs in HT29 and KM12L4 CRC cell lines. Further, VEGF stimulation resulted in enhanced cellular migration, which was effectively blocked by pharmacologic inhibition of VEGFR-1 or Src kinase. Correspondingly, migration studies using siRNA clones with reduced Src expression confirmed the requirement for Src in VEGF-induced migration in these cells. Furthermore, VEGF treatment enhanced VEGFR-1/SFK complex formation and increased tyrosine phosphorylation of focal adhesion kinase, p130 cas and paxillin. Finally, we demonstrate that VEGF-induced migration is not due, at least in part, to VEGF acting as a mitogen. These results suggest that VEGFR-1 promotes migration of tumour cells through a Src-dependent pathway linked to activation of focal adhesion components that regulate this process. PMID:16685275

Origin of Matrix-Producing Cells That Contribute to Aortic Fibrosis in Hypertension.

PubMed

Wu, Jing; Montaniel, Kim Ramil C; Saleh, Mohamed A; Xiao, Liang; Chen, Wei; Owens, Gary K; Humphrey, Jay D; Majesky, Mark W; Paik, David T; Hatzopoulos, Antonis K; Madhur, Meena S; Harrison, David G

2016-02-01

Various hypertensive stimuli lead to exuberant adventitial collagen deposition in large arteries, exacerbating blood pressure elevation and end-organ damage. Collagen production is generally attributed to resident fibroblasts; however, other cells, including resident and bone marrow-derived stem cell antigen positive (Sca-1(+)) cells and endothelial and vascular smooth muscle cells, can produce collagen and contribute to vascular stiffening. Using flow cytometry and immunofluorescence, we found that adventitial Sca-1(+) progenitor cells begin to produce collagen and acquire a fibroblast-like phenotype in hypertension. We also found that bone marrow-derived cells represent more than half of the matrix-producing cells in hypertension, and that one-third of these are Sca-1(+). Cell sorting and lineage-tracing studies showed that cells of endothelial origin contribute to no more than one fourth of adventitial collagen I(+) cells, whereas those of vascular smooth muscle lineage do not contribute. Our findings indicate that Sca-1(+) progenitor cells and bone marrow-derived infiltrating fibrocytes are major sources of arterial fibrosis in hypertension. Endothelial to mesenchymal transition likely also contributes, albeit to a lesser extent and pre-existing resident fibroblasts represent a minority of aortic collagen-producing cells in hypertension. This study shows that vascular stiffening represents a complex process involving recruitment and transformation of multiple cells types that ultimately elaborate adventitial extracellular matrix. © 2015 American Heart Association, Inc.

Hydraulic trade-offs and space filling enable better predictions of vascular structure and function in plants

PubMed Central

Savage, V. M.; Bentley, L. P.; Enquist, B. J.; Sperry, J. S.; Smith, D. D.; Reich, P. B.; von Allmen, E. I.

2010-01-01

Plant vascular networks are central to botanical form, function, and diversity. Here, we develop a theory for plant network scaling that is based on optimal space filling by the vascular system along with trade-offs between hydraulic safety and efficiency. Including these evolutionary drivers leads to predictions for sap flow, the taper of the radii of xylem conduits from trunk to terminal twig, and how the frequency of xylem conduits varies with conduit radius. To test our predictions, we use comprehensive empirical measurements of maple, oak, and pine trees and complementary literature data that we obtained for a wide range of tree species. This robust intra- and interspecific assessment of our botanical network model indicates that the central tendency of observed scaling properties supports our predictions much better than the West, Brown, and Enquist (WBE) or pipe models. Consequently, our model is a more accurate description of vascular architecture than what is given by existing network models and should be used as a baseline to understand and to predict the scaling of individual plants to whole forests. In addition, our model is flexible enough to allow the quantification of species variation around rules for network design. These results suggest that the evolutionary drivers that we propose have been fundamental in determining how physiological processes scale within and across plant species. PMID:21149696

Hydraulic trade-offs and space filling enable better predictions of vascular structure and function in plants.

PubMed

Savage, V M; Bentley, L P; Enquist, B J; Sperry, J S; Smith, D D; Reich, P B; von Allmen, E I

2010-12-28

Plant vascular networks are central to botanical form, function, and diversity. Here, we develop a theory for plant network scaling that is based on optimal space filling by the vascular system along with trade-offs between hydraulic safety and efficiency. Including these evolutionary drivers leads to predictions for sap flow, the taper of the radii of xylem conduits from trunk to terminal twig, and how the frequency of xylem conduits varies with conduit radius. To test our predictions, we use comprehensive empirical measurements of maple, oak, and pine trees and complementary literature data that we obtained for a wide range of tree species. This robust intra- and interspecific assessment of our botanical network model indicates that the central tendency of observed scaling properties supports our predictions much better than the West, Brown, and Enquist (WBE) or pipe models. Consequently, our model is a more accurate description of vascular architecture than what is given by existing network models and should be used as a baseline to understand and to predict the scaling of individual plants to whole forests. In addition, our model is flexible enough to allow the quantification of species variation around rules for network design. These results suggest that the evolutionary drivers that we propose have been fundamental in determining how physiological processes scale within and across plant species.

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.

Vascular Diseases

MedlinePlus

... vessels, such as diabetes or high cholesterol Smoking Obesity Losing weight, eating healthy foods, being active and not smoking can help vascular disease. Other treatments include medicines and surgery.

High-resolution vascular tissue characterization in mice using 55 MHz ultrasound hybrid imaging

PubMed Central

Mahmoud, Ahmed M.; Sandoval, Cesar; Teng, Bunyen; Schnermann, Jurgen B.; Martin, Karen H.; Mustafa, S. Jamal; Mukdadi, Osama M.

2012-01-01

Ultrasound and Duplex ultrasonography in particular are routinely used to diagnose cardiovascular disease (CVD), which is the leading cause of morbidity and mortality worldwide. However, these techniques may not be able to characterize vascular tissue compositional changes due to CVD. This work describes an ultrasound-based hybrid imaging technique that can be used for vascular tissue characterization and the diagnosis of atherosclerosis. Ultrasound radiofrequency (RF) data were acquired and processed in time, frequency, and wavelet domains to extract six parameters including time integrated backscatter (TIB), time variance (Tvar), time entropy (TE), frequency integrated backscatter (FIB), wavelet root mean square value (Wrms), and wavelet integrated backscatter (WIB). Each parameter was used to reconstruct an image co-registered to morphological B-scan. The combined set of hybrid images were used to characterize vascular tissue in vitro and in vivo using three mouse models including control (C57BL/6), and atherosclerotic apolipoprotein E-knockout (APOE-KO) and APOE/A1 adenosine receptor double knockout (DKO) mice. The technique was tested using high-frequency ultrasound including single-element (center frequency = 55 MHz) and commercial array (center frequency = 40 MHz) systems providing superior spatial resolutions of 24 μm and 40 μm, respectively. Atherosclerotic vascular lesions in the APOE-KO mouse exhibited the highest values (contrast) of −10.11 ± 1.92 dB, −12.13 ± 2.13 dB, −7.54 ± 1.45 dB, −5.10 ± 1.06 dB, −5.25 ± 0.94 dB, and −10.23 ± 2.12 dB in TIB, Tvar, TE, FIB, Wrms, WIB hybrid images (n = 10, p < 0.05), respectively. Control segments of normal vascular tissue showed the lowest values of −20.20 ± 2.71 dB, −22.54 ± 4.54 dB, −14.94 ± 2.05 dB, −9.64 ± 1.34 dB, −10.20 ± 1.27 dB, and −19.36 ± 3.24 dB in same hybrid images (n = 6, p < 0.05). Results from both histology and optical images showed good agreement with ultrasound findings within a maximum error of 3.6% in lesion estimation. This study demonstrated the feasibility of a high-resolution hybrid imaging technique to diagnose atherosclerosis and characterize plaque components in mouse. In the future, it can be easily implemented on commercial ultrasound systems and eventually translated into clinics as a screening tool for atherosclerosis and the assessment of vulnerable plaques. PMID:23218908

The Celution® System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System.

PubMed

Fraser, John K; Hicok, Kevin C; Shanahan, Rob; Zhu, Min; Miller, Scott; Arm, Douglas M

2014-01-01

Objective: To develop a closed, automated system that standardizes the processing of human adipose tissue to obtain and concentrate regenerative cells suitable for clinical treatment of thermal and radioactive burn wounds. Approach: A medical device was designed to automate processing of adipose tissue to obtain a clinical-grade cell output of stromal vascular cells that may be used immediately as a therapy for a number of conditions, including nonhealing wounds resulting from radiation damage. Results: The Celution ® System reliably and reproducibly generated adipose-derived regenerative cells (ADRCs) from tissue collected manually and from three commercial power-assisted liposuction devices. The entire process of introducing tissue into the system, tissue washing and proteolytic digestion, isolation and concentration of the nonadipocyte nucleated cell fraction, and return to the patient as a wound therapeutic, can be achieved in approximately 1.5 h. An alternative approach that applies ultrasound energy in place of enzymatic digestion demonstrates extremely poor efficiency cell extraction. Innovation: The Celution System is the first medical device validated and approved by multiple international regulatory authorities to generate autologous stromal vascular cells from adipose tissue that can be used in a real-time bedside manner. Conclusion: Initial preclinical and clinical studies using ADRCs obtained using the automated tissue processing Celution device described herein validate a safe and effective manner to obtain a promising novel cell-based treatment for wound healing.

Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

PubMed Central

Eklund, Lauri; Kangas, Jaakko; Saharinen, Pipsa

2016-01-01

Endothelial cells that form the inner layer of blood and lymphatic vessels are important regulators of vascular functions and centrally involved in the pathogenesis of vascular diseases. In addition to the vascular endothelial growth factor (VEGF) receptor pathway, the angiopoietin (Ang)–Tie system is a second endothelial cell specific ligand–receptor signalling system necessary for embryonic cardiovascular and lymphatic development. The Ang–Tie system also regulates postnatal angiogenesis, vessel remodelling, vascular permeability and inflammation to maintain vascular homoeostasis in adult physiology. This system is implicated in numerous diseases where the vasculature has an important contribution, such as cancer, sepsis, diabetes, atherosclerosis and ocular diseases. Furthermore, mutations in the TIE2 signalling pathway cause defects in vascular morphogenesis, resulting in venous malformations and primary congenital glaucoma. Here, we review recent advances in the understanding of the Ang–Tie signalling system, including cross-talk with the vascular endothelial protein tyrosine phosphatase (VE-PTP) and the integrin cell adhesion receptors, focusing on the Ang–Tie system in vascular development and pathogenesis of vascular diseases. PMID:27941161

Towards organ printing: engineering an intra-organ branched vascular tree

PubMed Central

Visconti, Richard P; Kasyanov, Vladimir; Gentile, Carmine; Zhang, Jing; Markwald, Roger R; Mironov, Vladimir

2013-01-01

Importance of the field Effective vascularization of thick three-dimensional engineered tissue constructs is a problem in tissue engineering. As in native organs, a tissue-engineered intra-organ vascular tree must be comprised of a network of hierarchically branched vascular segments. Despite this requirement, current tissue-engineering efforts are still focused predominantly on engineering either large-diameter macrovessels or microvascular networks. Areas covered in this review We present the emerging concept of organ printing or robotic additive biofabrication of an intra-organ branched vascular tree, based on the ability of vascular tissue spheroids to undergo self-assembly. What the reader will gain The feasibility and challenges of this robotic biofabrication approach to intra-organ vascularization for tissue engineering based on organ-printing technology using self-assembling vascular tissue spheroids including clinically relevantly vascular cell sources are analyzed. Take home message It is not possible to engineer 3D thick tissue or organ constructs without effective vascularization. An effective intra-organ vascular system cannot be built by the simple connection of large-diameter vessels and microvessels. Successful engineering of functional human organs suitable for surgical implantation will require concomitant engineering of a ‘built in’ intra-organ branched vascular system. Organ printing enables biofabrication of human organ constructs with a ‘built in’ intra-organ branched vascular tree. PMID:20132061

Joint scientific statement of the European Association for the Study of Obesity and the European Society of Hypertension: Obesity and early vascular ageing.

PubMed

Jordan, Jens; Nilsson, Peter M; Kotsis, Vasilios; Olsen, Michael H; Grassi, Guido; Yumuk, Volkan; Hauner, Hans; Zahorska-Markiewicz, Barbara; Toplak, Hermann; Engeli, Stefan; Finer, Nick

2015-03-01

Current cardiovascular risk scores do not include obesity or fat distribution as independent factors, and may underestimate risk in obese individuals. Assessment of early vascular ageing (EVA) biomarkers including arterial stiffness, central blood pressure, carotid intima-media thickness and flow-mediated vasodilation may help to refine risk assessment in obese individuals in whom traditional cardiovascular risk scores and factors suggest no need for specific medical attention. A number of issues need to be addressed before this approach is ready for translation into routine clinical practice. Methodologies for measurements of vascular markers need to be further standardized and less operator-dependent. The utility of these nontraditional risk factors will also need to be proven in sufficiently large and properly designed interventional studies. Indeed, published studies on vascular markers in obesity and weight loss vary in quality and study design, are sometimes conducted in small populations, use a variety of differing methodologies and study differing vascular beds. Finally, current vascular measurements are still crude and may not be sufficient to cover the different aspects of EVA in obesity.

Therapeutic strategies to combat neointimal hyperplasia in vascular grafts

PubMed Central

Collins, Michael J; Li, Xin; Lv, Wei; Yang, Chenzi; Protack, Clinton D; Muto, Akihito; Jadlowiec, Caroline C; Shu, Chang; Dardik, Alan

2012-01-01

Neointimal hyperplasia (NIH) in bypass conduits such as veins and prosthetic grafts is an important clinical entity that limits the long-term success of vascular interventions. Although the development of NIH in the conduits shares many of the same features of NIH that develops in native arteries after injury, vascular grafts are exposed to unique circumstances that predispose them to NIH, including surgical trauma related to vein handling, hemodynamic changes creating areas of low flow, and differences in biocompatibility between the conduit and the host environment. Multiple different approaches, including novel surgical techniques and targeted gene therapies, have been developed to target and prevent the causes of NIH. Recently, the PREVENT trials, the first molecular biology trials in vascular surgery aimed at preventing NIH, have failed to produce improved clinical outcomes, highlighting the incomplete knowledge of the pathways leading to NIH in vascular grafts. In this review, we aim to summarize the pathophysiologic pathways that underlie the formation of NIH in both vein and synthetic grafts and discuss current and potential mechanical and molecular approaches under investigation that may limit NIH in vascular grafts. PMID:22651839

Resection and reconstruction of pelvic and extremity soft tissue sarcomas with major vascular involvement: Current concepts

PubMed Central

McGoldrick, Niall P; Butler, Joseph S; Lavelle, Maire; Sheehan, Stephen; Dudeney, Sean; O'Toole, Gary C

2016-01-01

Soft tissue sarcoma accounts for approximately 1% of all cancers diagnosed annually in the United States. When these rare malignant mesodermal tumours arise in the pelvis and extremities, they may potentially encase or invade large calibre vascular structures. This presents a major challenge in terms of safe excision while also leaving acceptable surgical margins. In recent times, the trend has been towards limb salvage with vascular reconstruction in preference to amputation. Newer orthopaedic and vascular reconstructive techniques including both synthetic and autogenous graft reconstruction have made complex limb-salvage surgery feasible. Despite this, limb-salvage surgery with concomitant vascular reconstruction remains associated with higher rates of post-operative complications including infection and amputation. In this review we describe the initial presentation and investigation of patients presenting with soft tissue sarcomas in the pelvis and extremities, which involve vascular structures. We further discuss the key surgical reconstructive principles and techniques available for the management of these complex tumours, drawn from our institution’s experience as a national tertiary referral sarcoma service. PMID:27190757

Resection and reconstruction of pelvic and extremity soft tissue sarcomas with major vascular involvement: Current concepts.

PubMed

McGoldrick, Niall P; Butler, Joseph S; Lavelle, Maire; Sheehan, Stephen; Dudeney, Sean; O'Toole, Gary C

2016-05-18

Soft tissue sarcoma accounts for approximately 1% of all cancers diagnosed annually in the United States. When these rare malignant mesodermal tumours arise in the pelvis and extremities, they may potentially encase or invade large calibre vascular structures. This presents a major challenge in terms of safe excision while also leaving acceptable surgical margins. In recent times, the trend has been towards limb salvage with vascular reconstruction in preference to amputation. Newer orthopaedic and vascular reconstructive techniques including both synthetic and autogenous graft reconstruction have made complex limb-salvage surgery feasible. Despite this, limb-salvage surgery with concomitant vascular reconstruction remains associated with higher rates of post-operative complications including infection and amputation. In this review we describe the initial presentation and investigation of patients presenting with soft tissue sarcomas in the pelvis and extremities, which involve vascular structures. We further discuss the key surgical reconstructive principles and techniques available for the management of these complex tumours, drawn from our institution's experience as a national tertiary referral sarcoma service.

Tolerance in Nonhuman Primates by Delayed Mixed Chimerism

DTIC Science & Technology

2015-10-01

Vascularized composite allografts (VCA) are transplants containing multiple tissue types (including bone, muscle, skin, nerves and blood vessels), which offer...15 11. Appendices…………………………………………………………………………………. 15 4 INTRODUCTION Vascularized composite allografts (VCA) are...can be expected to lead to rapid translation into clinical trials. KEYWORDS Vascularized composite allograft, vascularized composite

A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis

PubMed Central

Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

2017-01-01

ABSTRACT. Background. Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. Objective: This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Methods: Medline, Web of Knowledge and PsycINFO were searched, using the terms: “vascular mild cognitive impairment” OR “vascular cognitive impairment no dementia” OR “vascular mild neurocognitive disorder” AND “dysexecutive” OR “executive function”. Meta-analyses were conducted for each of the selected tests, using random-effect models. Results: Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. Conclusion: A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control. PMID:29354217

New Radiotracers for Imaging of Vascular Targets in Angiogenesis-related Diseases

PubMed Central

Hong, Hao; Chen, Feng; Zhang, Yin; Cai, Weibo

2014-01-01

Tremendous advances over the last several decades in positron emission tomography (PET) and single photon emission computed tomography (SPECT) allow for targeted imaging of molecular and cellular events in the living systems. Angiogenesis, a multistep process regulated by the network of different angiogenic factors, has attracted world-wide interests, due to its pivotal role in the formation and progression of different diseases including cancer, cardiovascular diseases (CVD), and inflammation. In this review article, we will summarize the recent progress in PET or SPECT imaging of a wide variety of vascular targets in three major angiogenesis-related diseases: cancer, cardiovascular diseases, and inflammation. Faster drug development and patient stratification for a specific therapy will become possible with the facilitation of PET or SPECT imaging and it will be critical for the maximum benefit of patients. PMID:25086372

BIOLOGICAL AND BIOPHYSICAL PROPERTIES OF VASCULAR CONNEXIN CHANNELS

PubMed Central

Johnstone, Scott; Isakson, Brant; Locke, Darren

2010-01-01

Intercellular channels formed by connexin proteins play a pivotal role in the direct movement of ions and larger cytoplasmic solutes between vascular endothelial cells, between vascular smooth muscle cells, and between endothelial and smooth muscle cells. Multiple genetic and epigenetic factors modulate connexin expression levels and/or channel function, including cell type-independent and cell type-specific transcription factors, posttranslational modification and localized membrane targeting. Additionally, differences in protein-protein interactions, including those between connexins, significantly contribute to both vascular homeostasis and disease progression. The biophysical properties of the connexin channels identified in the vasculature, those formed by Cx37, Cx40, Cx43 and/or Cx45 proteins, are discussed in this review in the physiological and pathophysiological context of vessel function. PMID:19815177

Adverse Outcome Pathway (AOP) framework for embryonic vascular disruption and developmental defects (SOT)

EPA Science Inventory

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signal...

Fiber laser micromachining of thin NiTi tubes for shape memory vascular stents

NASA Astrophysics Data System (ADS)

Liu, Lei; Li, Dong Bo; Tong, Yi Fei; Zhu, Yu Fu

2016-07-01

Nickel titanium (NiTi) alloy has widely been used in the vascular stent manufacturing due to its excellent properties. Neodymium-doped yttrium aluminum garnet (Nd:YAG) laser is commonly used for the preparation of metal vascular stents. Recently, fiber lasers have been used for stent profiling for better cutting quality. To investigate the cutting-kerf characters of NiTi vascular stents fabricated by fiber laser cutting, laser cutting experiments with thin NiTi tubes were conducted in this study, while NiTi sheets were used in other fiber laser cutting studies. Different with striation topography, new topographies such as layer topography and topography mixed with layers and striations were observed, and the underlying reason for new topographies was also discussed. Comparative research on different topographies was conducted through analyzing the surface roughness, kerf width, heat-affected zone (HAZ) and dross formation. Laser cutting process parameters have a comprehensive influence on the cutting quality; in this study, the process parameters' influences on the cutting quality were studied from the view of power density along the cutting direction. The present research provides a guideline for improving the cutting quality of NiTi vascular stents.

Imaging of retinal and choroidal vascular tumours

PubMed Central

Heimann, H; Jmor, F; Damato, B

2013-01-01

The most common intraocular vascular tumours are choroidal haemangiomas, vasoproliferative tumours, and retinal haemangioblastomas. Rarer conditions include cavernous retinal angioma and arteriovenous malformations. Options for ablating the tumour include photodynamic therapy, argon laser photocoagulation, trans-scleral diathermy, cryotherapy, anti-angiogenic agents, plaque radiotherapy, and proton beam radiotherapy. Secondary effects are common and include retinal exudates, macular oedema, epiretinal membranes, retinal fibrosis, as well as serous and tractional retinal detachment, which are treated using standard methods (ie, intravitreal anti-angiogenic agents or steroids as well as vitreoretinal procedures, such as epiretinal membrane peeling and release of retinal traction). The detection, diagnosis, and monitoring of vascular tumours and their complications have improved considerably thanks to advances in imaging. These include spectral domain and enhanced depth imaging optical coherence tomography (SD-OCT and EDI-OCT, respectively), wide-angle photography and angiography as well as wide-angle fundus autofluorescence. Such novel imaging has provided new diagnostic clues and has profoundly influenced therapeutic strategies so that vascular tumours and secondary effects are now treated concurrently instead of sequentially, enhancing any opportunities for conserving vision and the eye. In this review, we describe how SD-OCT, EDI-OCT, autofluorescence, wide-angle photography and wide-angle angiography have facilitated the evaluation of eyes with the more common vascular tumours, that is, choroidal haemangioma, retinal vasoproliferative tumours, and retinal haemangioblastoma. PMID:23196648

Appearance of β-dystroglycan precedes the formation of glio-vascular end-feet in developing rat brain

PubMed Central

Kálmán, Mihály; Oszwald, Erzsébet; Adorján, István

2018-01-01

Dystroglycan has an important role in binding of perivascular glial end-feet to the basal lamina. Its β-subunit is localized in the glial end-feet. The investigation period lasted from E(embryonic day)12 to E20. Laminin and β-dystroglycan were detected by immunohistochemistry, the glial localization of the latter one was supported by electron microscopy. The immature glial structures were visualized by the immunostaining of nestin. The β-dystroglycan immunoreactivity appeared at E16 following the laminin of basal lamina but preceding the perivascular processes of radial glia (E18) and astrocyte-like cells (E20). It occurred in cell bodies which attached to the vessels directly but not with vascular processes and end-feet. The presence of β-dystroglycan in such immature cells may promote their differentiation to perivascular astrocytes and influence the formation of the glio-vascular processes.

Advanced ultrasound applications in the assessment of renal transplants: contrast-enhanced ultrasound, elastography, and B-flow.

PubMed

Morgan, Tara A; Jha, Priyanka; Poder, Liina; Weinstein, Stefanie

2018-04-09

Ultrasound is routinely used as the first imaging exam for evaluation of renal transplants and can identify most major surgical complications and evaluate vascularity with color Doppler. Ultrasound is limited, however, in the detection of parenchymal disease processes and Doppler evaluation is also prone to technical errors. Multiple new ultrasound applications have been developed and are under ongoing investigation which could add additional diagnostic capability to the routine ultrasound exam with minimal additional time, cost, and patient risk. Contrast-enhanced ultrasound (CEUS) can be used off-label in the transplant kidney, and can assist in detection of infection, trauma, and vascular complications. CEUS also can demonstrate perfusion of the transplant assessed quantitatively with generation of time-intensity curves. Future directions of CEUS include monitoring treatment response and microbubble targeted medication delivery. Elastography is an ultrasound application that can detect changes in tissue elasticity, which is useful to diagnose diffuse parenchymal disease, such as fibrosis, otherwise unrecognizable with ultrasound. Elastography has been successfully applied in other organs including the liver, thyroid, and breast; however, it is still under development for use in the transplant kidney. Unique properties of the transplant kidney including its heterogeneity, anatomic location, and other technical factors present challenges in the development of reference standard measurements. Lastly, B-flow imaging is a flow application derived from B-mode. This application can show the true lumen size of a vessel which is useful to depict vascular anatomy and bypasses some of the pitfalls of color Doppler such as demonstration of slow flow.

An Analytical Model for Determining Two-Dimensional Receptor-Ligand Kinetics

PubMed Central

Cheung, Luthur Siu-Lun; Konstantopoulos, Konstantinos

2011-01-01

Cell-cell adhesive interactions play a pivotal role in major pathophysiological vascular processes, such as inflammation, infection, thrombosis, and cancer metastasis, and are regulated by hemodynamic forces generated by blood flow. Cell adhesion is mediated by the binding of receptors to ligands, which are both anchored on two-dimensional (2-D) membranes of apposing cells. Biophysical assays have been developed to determine the unstressed (no-force) 2-D affinity but fail to disclose its dependence on force. Here we develop an analytical model to estimate the 2-D kinetics of diverse receptor-ligand pairs as a function of force, including antibody-antigen, vascular selectin-ligand, and bacterial adhesin-ligand interactions. The model can account for multiple bond interactions necessary to mediate adhesion and resist detachment amid high hemodynamic forces. Using this model, we provide a generalized biophysical interpretation of the counterintuitive force-induced stabilization of cell rolling observed by a select subset of receptor-ligand pairs with specific intrinsic kinetic properties. This study enables us to understand how single-molecule and multibond biophysics modulate the macroscopic cell behavior in diverse pathophysiological processes. PMID:21575567

Structural and functional imaging for vascular targeted photodynamic therapy

NASA Astrophysics Data System (ADS)

Li, Buhong; Gu, Ying; Wilson, Brian C.

2017-02-01

Vascular targeted photodynamic therapy (V-PDT) has been widely used for the prevention or treatment of vascular-related diseases, such as localized prostate cancer, wet age-related macular degeneration, port wine stains, esophageal varices and bleeding gastrointestinal mucosal lesions. In this study, the fundamental mechanisms of vascular responses during and after V-PDT will be introduced. Based on the V-PDT treatment of blood vessels in dorsal skinfold window chamber model, the structural and functional imaging, which including white light microscopy, laser speckle imaging, singlet oxygen luminescence imaging, and fluorescence imaging for evaluating vascular damage will be presented, respectively. The results indicate that vessel constriction and blood flow dynamics could be considered as the crucial biomarkers for quantitative evaluation of vascular damage. In addition, future perspectives of non-invasive optical imaging for evaluating vascular damage of V-PDT will be discussed.

Large scale serial two-photon microscopy to investigate local vascular changes in whole rodent brain models of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Delafontaine-Martel, P.; Lefebvre, J.; Damseh, R.; Castonguay, A.; Tardif, P.; Lesage, F.

2018-02-01

In this study, an automated serial two-photon microscope was used to image a fluorescent gelatin filled rodent's brain in 3D. A method to compute vascular density using automatic segmentation was combined with coregistration techniques to build group-level vasculature metrics. By studying the medial prefrontal cortex and the hippocampal formation of 3 age groups (2, 4.5 and 8 months old), we compared vascular density for both WT and an Alzheimer model transgenic brain (APP/PS1). We observe a loss of vascular density caused by the ageing process and we propose further analysis to confirm our results.

Role of oxidative stress and nitric oxide in atherothrombosis

PubMed Central

Lubos, Edith; Handy, Diane E.; Loscalzo, Joseph

2008-01-01

During the last decade basic and clinical research has highlighted the central role of reactive oxygen species (ROS) in cardiovascular disease. Enhanced production or attenuated degradation of ROS leads to oxidative stress, a process that affects endothelial and vascular function, and contributes to vascular disease. Nitric oxide (NO), a product of the normal endothelium, is a principal determinant of normal endothelial and vascular function. In states of inflammation, NO production by the vasculature increases considerably and, in conjunction with other ROS, contributes to oxidative stress. This review examines the role of oxidative stress and NO in mechanisms of endothelial and vascular dysfunction with an emphasis on atherothrombosis. PMID:18508590

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

PubMed Central

Hanson, Daniel R; Gottesman, Irving I

2005-01-01

Background Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. Discussion A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. Summary A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons. PMID:15707482

Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

PubMed

Cooke, Esther J; Zhou, Jenny Y; Wyseure, Tine; Joshi, Shweta; Bhat, Vikas; Durden, Donald L; Mosnier, Laurent O; Drygalski, Annette von

2018-06-01

Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterize synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty acutely painful joints in patients with haemophilia (PWH) were imaged by musculoskeletal ultrasound with Power Doppler (MSKUS/PD) to detect vascular abnormalities and bloody effusions. Nineteen out of 30 painful joint episodes in PWH were associated with haemarthrosis, and abnormal vascular perfusion was unique to bleeding joints. A model of induced haemarthrosis in factor VIII (FVIII)-deficient mice was used for histological assessment of vascular remodelling (α-smooth muscle actin [αSMA] expression), and monitoring of in vivo vascular perfusion and permeability by MSKUS/PD and albumin extravasation, respectively. Inflammatory (M1) and reparative (M2) macrophage markers were quantified in murine synovium over a 10-week time course by real-time polymerase chain reaction. The abnormal vascular perfusion observed in PWH was recapitulated in FVIII-deficient mice after induced haemarthrosis. Neovascularization and increased vessel permeability were apparent 2 weeks post-bleed in FVIII-deficient mice, after a transient elevation of inflammatory macrophage M1 markers. These vascular changes subsided by week 4, while vascular remodelling, evidenced by architectural changes and pronounced αSMA expression, persisted alongside a reparative macrophage M2 response. In conclusion, haemarthrosis leads to transient inflammation coupled with neovascularization and associated vascular permeability, while subsequent tissue repair mechanisms coincide with vascular remodelling. Together, these vascular changes may promote re-bleeding and HA progression. Schattauer GmbH Stuttgart.

Engineering clinically relevant volumes of vascularized bone

PubMed Central

Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

2015-01-01

Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. PMID:25877690

[Vascularization of the head and neck during development].

PubMed

Detrait, E; Etchevers, H C

2005-06-01

One of the earliest priorities of the embryonic vascular system is to ensure the metabolic needs of the head. This review covers some of the principles that govern the cellular assembly and localization of blood vessels in the head. In order to understand the development and organization of the cephalic vascular tree, one needs to recall the morphogenetic movements underlying vertebrate head formation and giving rise to the constituent cells of the vascular system. Some of the major signaling molecules involved in vascular development are discussed, including the angiopoietins, the endothelins, the FGFs, the Notch receptors, the PDGFs, Sonic hedgehog, the TGF family and the VEGFs, in order to underline similarities between embryonic and postnatal vascular development, even in the context of increasingly divergent form.

Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia A.; Vickerman, Mary B.; Keith, Patricia A.

2010-01-01

Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of humans, animals and plants is significantly modified in such extraterrestrial environments. One physiological requirement shared by humans with larger plants and animals is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. The VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

Mapping and Quantification of Vascular Branching in Plants, Animals and Humans by VESGEN Software

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, P. A.; Vickerman, M. B.; Keith, P. A.

2010-01-01

Humans face daunting challenges in the successful exploration and colonization of space, including adverse alterations in gravity and radiation. The Earth-determined biology of plants, animals and humans is significantly modified in such extraterrestrial environments. One physiological requirement shared by larger plants and animals with humans is a complex, highly branching vascular system that is dynamically responsive to cellular metabolism, immunological protection and specialized cellular/tissue function. VESsel GENeration (VESGEN) Analysis has been developed as a mature beta version, pre-release research software for mapping and quantification of the fractal-based complexity of vascular branching. Alterations in vascular branching pattern can provide informative read-outs of altered vascular regulation. Originally developed for biomedical applications in angiogenesis, VESGEN 2D has provided novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and other microvascular remodeling phenomena. Vascular trees, networks and tree-network composites are mapped and quantified. Applications include disease progression from clinical ophthalmic images of the human retina; experimental regulation of vascular remodeling in the mouse retina; avian and mouse coronary vasculature, and other experimental models in vivo. We envision that altered branching in the leaves of plants studied on ISS such as Arabidopsis thaliana cans also be analyzed.

The Populus class III HD ZIP, popREVOLUTA, influences cambium initiation and patterning of woody stems.

PubMed

Robischon, Marcel; Du, Juan; Miura, Eriko; Groover, Andrew

2011-03-01

The secondary growth of a woody stem requires the formation of a vascular cambium at an appropriate position and proper patterning of the vascular tissues derived from the cambium. Class III homeodomain-leucine zipper (HD ZIP) transcription factors have been implicated in polarity determination and patterning in lateral organs and primary vascular tissues and in the initiation and function of shoot apical meristems. We report here the functional characterization of a Populus class III HD ZIP gene, popREVOLUTA (PRE), that demonstrates another role for class III HD ZIPs in regulating the development of cambia and secondary vascular tissues. PRE is orthologous to Arabidopsis (Arabidopsis thaliana) REVOLUTA and is expressed in both the shoot apical meristem and in the cambial zone and secondary vascular tissues. Transgenic Populus expressing a microRNA-resistant form of PRE presents unstable phenotypic abnormalities affecting both primary and secondary growth. Surprisingly, phenotypic changes include abnormal formation of cambia within cortical parenchyma that can produce secondary vascular tissues in reverse polarity. Genes misexpressed in PRE mutants include transcription factors and auxin-related genes previously implicated in class III HD ZIP functions during primary growth. Together, these results suggest that PRE plays a fundamental role in the initiation of the cambium and in regulating the patterning of secondary vascular tissues.

Endothelial cell motility, coordination and pattern formation during vasculogenesis.

PubMed

Czirok, Andras

2013-01-01

How vascular networks assemble is a fundamental problem of developmental biology that also has medical importance. To explain the organizational principles behind vascular patterning, we must understand how can tissue level structures be controlled through cell behavior patterns like motility and adhesion that, in turn, are determined by biochemical signal transduction processes? We discuss the various ideas that have been proposed as mechanisms for vascular network assembly: cell motility guided by extracellular matrix alignment (contact guidance), chemotaxis guided by paracrine and autocrine morphogens, and multicellular sprouting guided by cell-cell contacts. All of these processes yield emergent patterns, thus endothelial cells can form an interconnected structure autonomously, without guidance from an external pre-pattern. © 2013 Wiley Periodicals, Inc.

Patient-based Outcomes and Quality of Life after Salvageable Wartime Extremity Vascular Injury

DTIC Science & Technology

2014-01-01

pattern. Reports on vascular injury from the civilian sector , including those using the National Trauma Data Bank , have been limited by an inability to...OIF/OEF) d Vascular injury ( AIS 2-6) d Vascular ICD-9 d No concomitant head injury d March 2002-August 2011 AIS , Abbreviated Injury Scale; ICD-9...had a greater proportion of patients who remained on active duty and fewer proportions of patients reporting unemployment (both P < .05). Group

Vascular ring complicates accidental button battery ingestion.

PubMed

Mercer, Ronald W; Schwartz, Matthew C; Stephany, Joshua; Donnelly, Lane F; Franciosi, James P; Epelman, Monica

2015-01-01

Button battery ingestion can lead to dangerous complications, including vasculoesophageal fistula formation. The presence of a vascular ring may complicate battery ingestion if the battery lodges at the level of the ring and its important vascular structures. We report a 4-year-old boy with trisomy 21 who was diagnosed with a vascular ring at the time of button battery ingestion and died 9 days after presentation due to massive upper gastrointestinal bleeding from esophageal erosion and vasculoesophageal fistula formation. Copyright © 2015 Elsevier Inc. All rights reserved.

[French Society of Vascular Medicine good medical practice guidelines on safety and environment in vascular medicine: Treatment of varicose veins].

PubMed

Giordana, P; Miserey, G

2014-12-01

These guidelines proposed by the French Society of Vascular Medicine define the optimal environment for vascular medicine practice: outpatient clinic; equipment, layout and maintenance of the care center; infection risk prevention (hand hygiene, individual protective measures, exposure to blood, ultrasound apparatus, etc.); common interventions and techniques (liquid and foam sclerotherapy, endovenous thermal treatments). These guidelines do not include phlebectomy and use of ultrasound contrast agents. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

USDA-ARS?s Scientific Manuscript database

In older adults, mildly elevated plasma total homocysteine (Hyperhomocysteinemia) is associated with increased risk of cognitive impairment, cerebrovascular disease and Alzheimer’s disease, but it is uncertain whether this is due to underlying metabolic, neurotoxic or vascular processes. We report h...

Use of Adipose Derived Stem Cells to Treat Large Bone Defects. Addendum

DTIC Science & Technology

2009-07-01

optimal delivery . We have also completed characterization of our segmental defect model, including analysis of vascular ingrowth during defect healing...cells seeded in 1.2% Keltone alginate at a density of 12-15x106cells/ml were loaded on 24-well transwell insert membranes [6]. Once hydrogel discs...process from tissue culture plates and hydrogels does not alter the surface phenotype. Gene expression of surface markers and proteins associated with

Nanoparticle transport and delivery in a heterogeneous pulmonary vasculature.

PubMed

Sohrabi, Salman; Wang, Shunqiang; Tan, Jifu; Xu, Jiang; Yang, Jie; Liu, Yaling

2017-01-04

Quantitative understanding of nanoparticles delivery in a complex vascular networks is very challenging because it involves interplay of transport, hydrodynamic force, and multivalent interactions across different scales. Heterogeneous pulmonary network includes up to 16 generations of vessels in its arterial tree. Modeling the complete pulmonary vascular system in 3D is computationally unrealistic. To save computational cost, a model reconstructed from MRI scanned images is cut into an arbitrary pathway consisting of the upper 4-generations. The remaining generations are represented by an artificially rebuilt pathway. Physiological data such as branch information and connectivity matrix are used for geometry reconstruction. A lumped model is used to model the flow resistance of the branches that are cut off from the truncated pathway. Moreover, since the nanoparticle binding process is stochastic in nature, a binding probability function is used to simplify the carrier attachment and detachment processes. The stitched realistic and artificial geometries coupled with the lumped model at the unresolved outlets are used to resolve the flow field within the truncated arterial tree. Then, the biodistribution of 200nm, 700nm and 2µm particles at different vessel generations is studied. At the end, 0.2-0.5% nanocarrier deposition is predicted during one time passage of drug carriers through pulmonary vascular tree. Our truncated approach enabled us to efficiently model hemodynamics and accordingly particle distribution in a complex 3D vasculature providing a simple, yet efficient predictive tool to study drug delivery at organ level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Glatiramer acetate (GA) prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway

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

Wei, Guoqian; Zhang, Xueyan; Su, Zhendong

2015-01-30

Highlights: • GA inhibited TNF-α-induced binding of monocytes to endothelial cells. • GA inhibited the induction of adhesion molecules MCP-1, VCAM-1 and E-selectin. • GA inhibits NF-κB p65 nuclear translocation and transcriptional activity. • GA inhibits TNF-α-induced IκBα degradation. - Abstract: Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) is considered to be the major one contributing to the process of development of endothelial dysfunction. Exposure to TNF-α induces the expression of a number of proinflammatory chemokines, such as monocyte chemotactic protein-1 (MCP-1), and adhesion molecules, including vascular adhesion molecule-1 (VCAM-1) and E-selectin, which mediate the interaction of invading monocytesmore » with vascular endothelial cells. Glatiramer acetate (GA) is a licensed clinical drug for treating patients suffering from multiple sclerosis (MS). The effects of GA in vascular disease have not shown before. In this study, we found that GA significantly inhibited TNF-α-induced binding of monocytes to endothelial cells. Mechanistically, we found that GA ameliorated the upregulation of MCP-1, VCAM-1, and E-selectin induced by TNF-α. Notably, this process is mediated by inhibiting the nuclear translocation and activation of NF-κB. Our results also indicate that GA pretreatment attenuates the up-regulation of COX-2 and iNOS. These data suggest that GA might have a potential benefit in therapeutic endothelial dysfunction related diseases.« less

Checklist of the vascular plants of Steamboat Mountain Research Natural Area.

Treesearch

S. Reid Schuller; Robert E. Frenkel

1981-01-01

Lists 237 vascular plant taxa found in the 570-hectare Steamboat Mountain Research Natural Area. Notes on habitats, community types, and abundance are included for most taxa. This research note provides scientists, educators, and land managers with baseline information on the presence, location, and abundance of vascular plants within the Steamboat Mountain Research...

EphrinA1 Inhibits Vascular Endothelial Growth Factor-Induced Intracellular Signaling and Suppresses Retinal Neovascularization and Blood-Retinal Barrier Breakdown

PubMed Central

Ojima, Tomonari; Takagi, Hitoshi; Suzuma, Kiyoshi; Oh, Hideyasu; Suzuma, Izumi; Ohashi, Hirokazu; Watanabe, Daisuke; Suganami, Eri; Murakami, Tomoaki; Kurimoto, Masafumi; Honda, Yoshihito; Yoshimura, Nagahisa

2006-01-01

The Eph receptor/ephrin system is a recently discovered regulator of vascular development during embryogenesis. Activation of EphA2, one of the Eph receptors, reportedly suppresses cell proliferation and adhesion in a wide range of cell types, including vascular endothelial cells. Vascular endothelial growth factor (VEGF) plays a primary role in both pathological angiogenesis and abnormal vascular leakage in diabetic retinopathy. In the study described herein, we demonstrated that EphA2 stimulation by ephrinA1 in cultured bovine retinal endothelial cells inhibits VEGF-induced VEGFR2 receptor phosphorylation and its downstream signaling cascades, including PKC (protein kinase C)-ERK (extracellular signal-regulated kinase) 1/2 and Akt. This inhibition resulted in the reduction of VEGF-induced angiogenic cell activity, including migration, tube formation, and cellular proliferation. These inhibitory effects were further confirmed in animal models. Intraocular injection of ephrinA1 suppressed ischemic retinal neovascularization in a dose-dependent manner in a mouse model. At a dose of 125 ng/eye, the inhibition was 36.0 ± 14.9% (P < 0.001). EphrinA1 also inhibited VEGF-induced retinal vascular permeability in a rat model by 46.0 ± 10.0% (P < 0.05). These findings suggest a novel therapeutic potential for EphA2/ephrinA1 in the treatment of neovascularization and vasopermeability abnormalities in diabetic retinopathy. PMID:16400034

Fabrication of viable and functional pre-vascularized modular bone tissues by coculturing MSCs and HUVECs on microcarriers in spinner flasks.

PubMed

Zhang, Songjie; Zhou, Min; Ye, Zhaoyang; Zhou, Yan; Tan, Wen-Song

2017-08-01

Slow vascularization often impedes the viability and function of engineered bone replacements. Prevascularization is a promising way to solve this problem. In this study, a new process was developed by integrating microcarrier culture and coculture to fabricate pre-vascularized bone microtissues with mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs). Initially, coculture medium and cell ratio between MSCs and HUVECs were optimized in tissue culture plates concerning cell proliferation, osteogenesis and angiogenesis. Subsequently, cells were seeded onto CultiSpher S microcarriers in spinner flasks and subjected to a two-stage (proliferative-osteogenic) culture process for four weeks. Both cells proliferated and functioned well in chosen medium and a 1 : 1 ratio between MSCs and HUVECs was chosen for better angiogenesis. After four weeks of culture in spinner flasks, the microtissues were formed with high cellularity, evenly distributed cells and tube formation ability. While coculture with HUVECs exerted an inhibitory effect on osteogenic differentiation of MSCs, with downregulated alkaline phosphatase activity, mineralization and gene expression of COLI, RUNX2 and OCN, this could be attenuated by employing a delayed seeding strategy of HUVECs against MSCs during the microtissue fabrication process. Collectively, this work established an effective method to fabricate pre-vascularized bone microtissues, which would lay a solid foundation for subsequent development of vascularized tissue grafts for bone regeneration. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Damage Control for Vascular Trauma from the Prehospital to the Operating Room Setting.

PubMed

Pikoulis, Emmanouil; Salem, Karim M; Avgerinos, Efthymios D; Pikouli, Anastasia; Angelou, Anastasios; Pikoulis, Antreas; Georgopoulos, Sotirios; Karavokyros, Ioannis

2017-01-01

Early management of vascular injury, starting at the field, is imperative for survival no less than any operative maneuver. Contemporary prehospital management of vascular trauma, including appropriate fluid and volume infusion, tourniquets, and hemostatic agents, has reversed the historically known limb hemorrhage as a leading cause of death. In this context, damage control (DC) surgery has evolved to DC resuscitation (DCR) as an overarching concept that draws together preoperative and operative interventions aiming at rapidly reducing bleeding from vascular disruption, optimizing oxygenation, and clinical outcomes. This review addresses contemporary DCR techniques from the prehospital to the surgical setting, focusing on civilian vascular injuries.

Three-dimensional Hessian matrix-based quantitative vascular imaging of rat iris with optical-resolution photoacoustic microscopy in vivo

NASA Astrophysics Data System (ADS)

Zhao, Huangxuan; Wang, Guangsong; Lin, Riqiang; Gong, Xiaojing; Song, Liang; Li, Tan; Wang, Wenjia; Zhang, Kunya; Qian, Xiuqing; Zhang, Haixia; Li, Lin; Liu, Zhicheng; Liu, Chengbo

2018-04-01

For the diagnosis and evaluation of ophthalmic diseases, imaging and quantitative characterization of vasculature in the iris are very important. The recently developed photoacoustic imaging, which is ultrasensitive in imaging endogenous hemoglobin molecules, provides a highly efficient label-free method for imaging blood vasculature in the iris. However, the development of advanced vascular quantification algorithms is still needed to enable accurate characterization of the underlying vasculature. We have developed a vascular information quantification algorithm by adopting a three-dimensional (3-D) Hessian matrix and applied for processing iris vasculature images obtained with a custom-built optical-resolution photoacoustic imaging system (OR-PAM). For the first time, we demonstrate in vivo 3-D vascular structures of a rat iris with a the label-free imaging method and also accurately extract quantitative vascular information, such as vessel diameter, vascular density, and vascular tortuosity. Our results indicate that the developed algorithm is capable of quantifying the vasculature in the 3-D photoacoustic images of the iris in-vivo, thus enhancing the diagnostic capability of the OR-PAM system for vascular-related ophthalmic diseases in vivo.

Cytocompatibility and biologic characteristics of synthetic scaffold materials of rabbit acellular vascular matrix combining with human-like collagen I.

PubMed

Liu, Xuqian; Wang, Jie; Dong, Fusheng; Song, Peng; Tian, Songbo; Li, Hexiang; Hou, Yali

2017-10-01

Scaffold material provides a three-dimensional growing environment for seed cells in the research field of tissue engineering. In the present study, rabbit arterial blood vessel cells were chemically removed with trypsin and Triton X-100 to prepare rabbit acellular vascular matrix scaffold material. Observation by He&Masson staining revealed that no cellular components or nuclei existed in the vascular intima and media after decellularization. Human-like collagen I was combined with acellular vascular matrix by freeze-drying to prepare an acellular vascular matrix-0.25% human-like collagen I scaffold to compensate for the extracellular matrix loss during the decellularization process. We next performed a series of experiments to test the water absorbing quality, biomechanics, pressure resistance, cytotoxicity, and ultra-micro structure of the acellular vascular matrix composite material and natural rabbit artery and found that the acellular vascular matrix-0.25% human-like collagen I material behaved similarly to natural rabbit artery. In conclusion, the acellular vascular matrix-0.25% human-like collagen I composite material provides a new approach and lays the foundation for novel scaffold material research into tissue engineering of blood vessels.

Does erectile tissue angioarchitecture modify with aging? An immunohistological and morphometric approach.

PubMed

Costa, Carla; Vendeira, Pedro

2008-04-01

Introduction. Erectile dysfunction is a common problem in aged men; however, which vascular cavernosal alterations occur with age progression remain unclarified. Aim. Using cavernosal tissue from rats of various ages, we aimed to thoroughly assess erectile vascular-associated morphologic, immunohistological, and morphometric alterations during aging. Methods. Male Wistar rats were divided according to age in groups of 2, 6, 12, 18, 24 months old (N = 5). Cavernosal tissue of all groups was collected and processed for morphologic evaluation, immunodetection of alpha-smooth muscle actin and von Willebrand factor and morphometric quantification of vascular and smooth muscle cell (SMC) areas. Main Outcome Measures. The morphometric assessment of age-related alterations in cavernosal vascular and SMCs using the ImageJ image-processing program. Results. Morphologic and immunohistological evaluation showed a similar structure of erectile tissue among all age groups, divided in two cavernosal bodies containing numerous sinusoidal vascular spaces surrounded by SMCs. Additionally, we observed a reduction of SMC content and an increase in the caliber of vascular spaces, with aging. This was confirmed by the morphometric quantification of the vascular and SMC areas (mean area x10(3) microm(2) +/- x10(3) standard error). Two-month-old animals had a mean vascular area of 4.21 +/- 0.51, approximately 3.5-fold less than the 6-month-old group. The differences increased when comparing the youngest groups with the 12-, 18-, and 24-month-old animals, with mean measurements of 18.99 +/- 1.91, 25.23 +/- 2.76, and 26.34 +/- 2.97. Conversely, SMC areas progressively decreased between 2- and 6-month-old animals, from 6.75 +/- 0.90 to 6.38 +/- 1.24. The elderly 12-, 18-, and 24-month-old groups presented an approximated 1.5-fold reduction on SMCs area, showed by the respective measurements of 4.11 +/- 0.50, 4.01 +/- 0.35, and 4.02 +/- 0.44. Conclusions. We demonstrated that cavernosal angioarchitecture was modified with aging. The decrease in SMCs and the considerable enlargement of vascular lumens may limit the basic function of penile vascular tree in the elderly.

Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

PubMed

Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

2016-01-01

The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Small Artery Elastin Distribution and Architecture-Focus on Three Dimensional Organization.

PubMed

Hill, Michael A; Nourian, Zahra; Ho, I-Lin; Clifford, Philip S; Martinez-Lemus, Luis; Meininger, Gerald A

2016-11-01

The distribution of ECM proteins within the walls of resistance vessels is complex both in variety of proteins and structural arrangement. In particular, elastin exists as discrete fibers varying in orientation across the adventitia and media as well as often resembling a sheet-like structure in the case of the IEL. Adding to the complexity is the tissue heterogeneity that exists in these structural arrangements. For example, small intracranial cerebral arteries lack adventitial elastin while similar sized arteries from skeletal muscle and intestinal mesentery exhibit a complex adventitial network of elastin fibers. With regard to the IEL, several vascular beds exhibit an elastin sheet with punctate holes/fenestrae while in others the IEL is discontinuous and fibrous in appearance. Importantly, these structural patterns likely sub-serve specific functional properties, including mechanosensing, control of external forces, mechanical properties of the vascular wall, cellular positioning, and communication between cells. Of further significance, these processes are altered in vascular disorders such as hypertension and diabetes mellitus where there is modification of ECM. This brief report focuses on the three-dimensional wall structure of small arteries and considers possible implications with regard to mechanosensing under physiological and pathophysiological conditions. © 2016 John Wiley & Sons Ltd.

Fetal median sacral artery anatomy study by micro-CT imaging.

PubMed

Meignan, P; Binet, A; Cook, A R; Lardy, H; Captier, G

2018-04-30

The median sacral artery (MSA) is the termination of the dorsal aorta, which undergoes a complex regression and remodeling process during embryo and fetal development. The MSA contributes to the pelvic vascularization and may be injured during pelvic surgery. The embryological steps of MSA development, anastomosis formation and anatomical variations are linked, but not fully understood. The pelvic vascularization and more precisely the MSA of a human fetus at 22 weeks of gestation (GW) were studied using micro-CT imaging. Image treatment included arterial segmentations and 3D visualization. At 22 GW, the MSA was a well-developed straight artery in front of the sacrum and was longer than the abdominal aorta. Anastomoses between the MSA and the internal pudendal arteries and the superior rectal artery were detected. No evidence was found for the existence of a coccygeal glomus with arteriovenous anastomosis. Micro-CT imaging and 3D visualization helped us understand the MSA central role in pelvic vascularization through the ilio-aortic anastomotic system. It is essential to know this anastomotic network to treat pathological conditions, such as sacrococcygeal teratomas and parasitic ischiopagus twins (for instance, fetus in fetu and twin-reversed arterial perfusion sequence).

Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing

PubMed Central

Seals, Douglas R.

2016-01-01

Abstract Calorie restriction (CR) in the absence of malnutrition exerts a multitude of physiological benefits with ageing in model organisms and in humans including improvements in vascular function. Despite the well‐known benefits of chronic CR, long‐term energy restriction is not likely to be a feasible healthy lifestyle strategy in humans due to poor sustained adherence, and presents additional concerns if applied to normal weight older adults. This review summarizes what is known about the effects of CR on vascular function with ageing including the underlying molecular ‘energy‐ and nutrient‐sensing’ mechanisms, and discusses the limited but encouraging evidence for alternative pharmacological and lifestyle interventions that may improve vascular function with ageing by mimicking the beneficial effects of long‐term CR. PMID:27641062

High resolution neurography of the brachial plexus by 3 Tesla magnetic resonance imaging.

PubMed

Cejas, C; Rollán, C; Michelin, G; Nogués, M

2016-01-01

The study of the structures that make up the brachial plexus has benefited particularly from the high resolution images provided by 3T magnetic resonance scanners. The brachial plexus can have mononeuropathies or polyneuropathies. The mononeuropathies include traumatic injuries and trapping, such as occurs in thoracic outlet syndrome due to cervical ribs, prominent transverse apophyses, or tumors. The polyneuropathies include inflammatory processes, in particular chronic inflammatory demyelinating polyneuropathy, Parsonage-Turner syndrome, granulomatous diseases, and radiation neuropathy. Vascular processes affecting the brachial plexus include diabetic polyneuropathy and the vasculitides. This article reviews the anatomy of the brachial plexus and describes the technique for magnetic resonance neurography and the most common pathologic conditions that can affect the brachial plexus. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Clinicopathological correlation of psychosis and brain vascular changes in Alzheimer's disease.

PubMed

Ting, Simon Kang Seng; Hao, Ying; Chia, Pei Shi; Tan, Eng-King; Hameed, Shahul

2016-02-12

Psychosis is common in Alzheimer's disease (AD). However, studies on neuropathology in vascular etiology contributing to psychosis in AD is lacking to date. The aim of this study was to investigate neuropathological vascular related changes in Alzheimer's disease with psychosis. Data of patients with AD from the National Alzheimer's Coordinating Center between 2005 to September 2013 was accessed and reviewed. Presence of psychosis was determined based on Neuropsychiatric Inventory Questionnaire taken from the last visit within one year prior to death, and patients were divided into psychosis positive and negative group. Comparison of clinical details and neuropathological vascular changes between the groups was performed using Wilcoxon rank sum test and Chi-square/ Fisher's exact test. Significant variables were further included in a multivariate logistic model. Overall, 145 patients was included. Of these, 50 patients were psychosis positive. Presence of one or more cortical microinfarcts and moderate to severe arteriosclerosis was found to be positively associated with psychosis. Our results suggest vascular changes correlate with psychosis in Alzheimer's disease.

The influence of a Vascular Surgery Hospitalist program on physician and patient satisfaction, resident education, and resource utilization.

PubMed

Cull, David L; Langan, Eugene M; Taylor, Spence M; Carsten, Christopher G; Tong, Angie; Johnson, Brent

2013-10-01

A number of surgery practice models have been developed to address general and trauma surgeon workforce shortages and on-call issues and to improve surgeon satisfaction. These include the creation of acute or urgent care surgery services and "surgical hospitalist" programs. To date, no practice models corresponding to those developed for general and trauma surgeons have been proposed to address these same issues among vascular surgeons or other surgical subspecialists. In 2003, our practice established a Vascular Surgery Hospitalist program. Since its inception nearly a decade ago, it has undergone several modifications. We reviewed hospital administrative databases and surveys of faculty, residents, and patients to evaluate the program's impact. Benefits of the Vascular Surgery Hospitalist program include improved surgeon satisfaction, resource utilization, timeliness of patient care, communication among referring physicians and ancillary staff, and resident teaching/supervision. Elements of this program may be applicable to a variety of surgical subspecialty settings. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Matrix ageing and vascular impacts: focus on elastin fragmentation.

PubMed

Duca, Laurent; Blaise, Sébastien; Romier, Béatrice; Laffargue, Muriel; Gayral, Stéphanie; El Btaouri, Hassan; Kawecki, Charlotte; Guillot, Alexandre; Martiny, Laurent; Debelle, Laurent; Maurice, Pascal

2016-06-01

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and represent a major problem of public health. Over the years, life expectancy has considerably increased throughout the world, and the prevalence of CVD is inevitably rising with the growing ageing of the population. The normal process of ageing is associated with progressive deterioration in structure and function of the vasculature, commonly called vascular ageing. At the vascular level, extracellular matrix (ECM) ageing leads to molecular alterations in long half-life proteins, such as elastin and collagen, and have critical effects on vascular diseases. This review highlights ECM alterations occurring during vascular ageing with a specific focus on elastin fragmentation and also the contribution of elastin-derived peptides (EDP) in age-related vascular complications. Moreover, current and new pharmacological strategies aiming at minimizing elastin degradation, EDP generation, and associated biological effects are discussed. These strategies may be of major relevance for preventing and/or delaying vascular ageing and its complications. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Vascular Endothelial Growth Factor (VEGF) and Platelet (PF-4) Factor 4 Inputs Modulate Human Microvascular Endothelial Signaling in a Three-Dimensional Matrix Migration Context*

PubMed Central

Hang, Ta-Chun; Tedford, Nathan C.; Reddy, Raven J.; Rimchala, Tharathorn; Wells, Alan; White, Forest M.; Kamm, Roger D.; Lauffenburger, Douglas A.

2013-01-01

The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial postwound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage before progression of wound healing toward tissue homeostasis. Because of its early presence and high concentration, the angiostatic chemokine platelet factor 4, which can induce endothelial anoikis, can strongly affect angiogenesis. In our work, we explored signaling crosstalk interactions between vascular endothelial growth factor and platelet factor 4 using phosphotyrosine-enriched mass spectrometry methods on human dermal microvascular endothelial cells cultured under conditions facilitating migratory sprouting into collagen gel matrices. We developed new methods to enable mass spectrometry-based phosphorylation analysis of primary cells cultured on collagen gels, and quantified signaling pathways over the first 48 h of treatment with vascular endothelial growth factor in the presence or absence of platelet factor 4. By observing early and late signaling dynamics in tandem with correlation network modeling, we found that platelet factor 4 has significant crosstalk with vascular endothelial growth factor by modulating cell migration and polarization pathways, centered around P38α MAPK, Src family kinases Fyn and Lyn, along with FAK. Interestingly, we found EphA2 correlational topology to strongly involve key migration-related signaling nodes after introduction of platelet factor 4, indicating an influence of the angiostatic factor on this ambiguous but generally angiogenic signal in this complex environment. PMID:24023389

Disruptive technological advances in vascular access for dialysis: an overview.

PubMed

Yeo, Wee-Song; Ng, Qin Xiang

2017-11-29

End-stage kidney disease (ESKD), one of the most prevalent diseases in the world and with increasing incidence, is associated with significant morbidity and mortality. Current available modes of renal replacement therapy (RRT) include dialysis and renal transplantation. Though renal transplantation is the preferred and ideal mode of RRT, this modality may not be available to all patients with ESKD. Moreover, renal transplant recipients are constantly at risk of complications associated with immunosuppression and immunosuppressant use, and posttransplant lymphoproliferative disorder. Dialysis may be the only available modality in certain patients. However, dialysis has its limitations, which include issues associated with lack of vascular access, risks of infections and vascular thrombosis, decreased quality of life, and absence of biosynthetic functions of the kidney. In particular, the creation and maintenance of hemodialysis vascular access in children poses a unique set of challenges to the pediatric nephrologist owing to the smaller vessel diameters and vascular hyperreactivity compared with adult patients. Vascular access issues continue to be one of the major limiting factors prohibiting the delivery of adequate dialysis in ESKD patients and is the Achilles' heel of hemodialysis. This review aims to provide a critical overview of disruptive technological advances and innovations for vascular access. Novel strategies in preventing neointimal hyperplasia, novel bioengineered products, grafts and devices for vascular access will be discussed. The potential impact of these solutions on improving the morbidity encountered by dialysis patients will also be examined.

Amplatzer vascular plug for arteriovenous hemodialysis access occlusion: initial experience.

PubMed

Bui, J T; Gaba, R C; Knuttinen, M G; West, D L; Owens, C A

2009-01-01

The Amplatzer Vascular Plug (AVP; AGA Medical, Golden Valley, MN) is a recently developed self-expanding metallic device indicated for peripheral vascular embolizations. Herein, we describe use of this device in the treatment of vascular complications related to arteriovenous hemodialysis fistulas and grafts. This HIPAA compliant retrospective study was approved by the institutional review board with informed consent waived. Six patients with problematic arteriovenous access underwent access occlusion using the AVP. Procedure indications included vascular steal syndrome in five patients, and enlarging vascular aneurysms in one patient. Contraindications for surgical correction were determined by the referring surgeon. AVP embolizations were performed using devices oversized by 50% introduced through vascular sheaths positioned within vein segments just beyond the arteriovenous anastomoses. Noninvasive evaluation of the involved extremity was performed pre- and post-embolization in addition to clinical follow-up examinations. Measured outcomes included success of angiographic occlusion, improvement in distal arterial flow, AVP number, AVP diameter, time to access occlusion, and clinical symptomatic improvement. Technical success was 100%, with complete arteriovenous access occlusion accomplished in all cases, with an average of 1.5 AVPs used per patient. Mean time to access occlusion was 19.3 minutes. Angiographic improvement in distal arterial flow was immediately evident and resolution of clinical symptoms occurred in all patients, with mean long-term follow-up of 16 months. No procedure-related complications were encountered. The Amplatzer Vascular Plug provides a minimally invasive and efficacious method for embolization of problematic arteriovenous hemodialysis access.

Protecting against vascular disease in brain

PubMed Central

2011-01-01

Endothelial cells exert an enormous influence on blood vessels throughout the circulation, but their impact is particularly pronounced in the brain. New concepts have emerged recently regarding the role of this cell type and mechanisms that contribute to endothelial dysfunction and vascular disease. Activation of the renin-angiotensin system plays a prominent role in producing these abnormalities. Both oxidative stress and local inflammation are key mechanisms that underlie vascular disease of diverse etiology. Endogenous mechanisms of vascular protection are also present, including antioxidants, anti-inflammatory molecules, and peroxisome proliferator-activated receptor-γ. Despite their clear importance, studies of mechanisms that underlie cerebrovascular disease continue to lag behind studies of vascular biology in general. Identification of endogenous molecules and pathways that protect the vasculature may result in targeted approaches to prevent or slow the progression of vascular disease that causes stroke and contributes to the vascular component of dementia and Alzheimer's disease. PMID:21335467

Open and endovascular aneurysm repair in the Society for Vascular Surgery Vascular Quality Initiative.

PubMed

Spangler, Emily L; Beck, Adam W

2017-12-01

The Society for Vascular Surgery Vascular Quality Initiative is a patient safety organization and a collection of procedure-based registries that can be utilized for quality improvement initiatives and clinical outcomes research. The Vascular Quality Initiative consists of voluntary participation by centers to collect data prospectively on all consecutive cases within specific registries which physicians and centers elect to participate. The data capture extends from preoperative demographics and risk factors (including indications for operation), through the perioperative period, to outcomes data at up to 1-year of follow-up. Additionally, longer-term follow-up can be achieved by matching with Medicare claims data, providing long-term longitudinal follow-up for a majority of patients within the Vascular Quality Initiative registries. We present the unique characteristics of the Vascular Quality Initiative registries and highlight important insights gained specific to open and endovascular abdominal aortic aneurysm repair. Copyright © 2017 Elsevier Inc. All rights reserved.

The vascular basement membrane in the healthy and pathological brain.

PubMed

Thomsen, Maj S; Routhe, Lisa J; Moos, Torben

2017-10-01

The vascular basement membrane contributes to the integrity of the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The BCECs receive support from pericytes embedded in the vascular basement membrane and from astrocyte endfeet. The vascular basement membrane forms a three-dimensional protein network predominantly composed of laminin, collagen IV, nidogen, and heparan sulfate proteoglycans that mutually support interactions between BCECs, pericytes, and astrocytes. Major changes in the molecular composition of the vascular basement membrane are observed in acute and chronic neuropathological settings. In the present review, we cover the significance of the vascular basement membrane in the healthy and pathological brain. In stroke, loss of BBB integrity is accompanied by upregulation of proteolytic enzymes and degradation of vascular basement membrane proteins. There is yet no causal relationship between expression or activity of matrix proteases and the degradation of vascular matrix proteins in vivo. In Alzheimer's disease, changes in the vascular basement membrane include accumulation of Aβ, composite changes, and thickening. The physical properties of the vascular basement membrane carry the potential of obstructing drug delivery to the brain, e.g. thickening of the basement membrane can affect drug delivery to the brain, especially the delivery of nanoparticles.

Functional preservation of vascular smooth muscle tissue

NASA Technical Reports Server (NTRS)

Alexander, W. C.; Hutchins, P. M.; Kimzey, S. L.

1973-01-01

The ionic and cellular feedback relationships operating to effect the vascular decompensatory modifications were examined to reveal procedures for implementing protective measures guarding against vascular collapse when returning from a weightless environment to that of the earth's gravity. The surgical procedures for preparing the rat cremaster, and the fixation methods are described. Abstracts of publications resulting from this research are included.

Retrospective Study on Laser Treatment of Oral Vascular Lesions Using the "Leopard Technique": The Multiple Spot Irradiation Technique with a Single-Pulsed Wave.

PubMed

Miyazaki, Hidetaka; Ohshiro, Takafumi; Romeo, Umberto; Noguchi, Tadahide; Maruoka, Yutaka; Gaimari, Gianfranco; Tomov, Georgi; Wada, Yoshitaka; Tanaka, Kae; Ohshiro, Toshio; Asamura, Shinichi

2018-06-01

This study aimed to retrospectively evaluate the efficacy and safety of laser treatment of oral vascular lesions using the multiple spot irradiation technique with a single-pulsed wave. In laser therapy for vascular lesions, heat accumulation induced by excessive irradiation can cause adverse events postoperatively, including ulcer formation, resultant scarring, and severe pain. To prevent heat accumulation and side effects, we have applied a multiple pulsed spot irradiation technique, the so-called "leopard technique" (LT) to oral vascular lesions. This approach was originally proposed for laser treatment of nevi. It can avoid thermal concentration at the same spot and spare the epithelium, which promotes smooth healing. The goal of the study was to evaluate this procedure and treatment outcomes. The subjects were 46 patients with 47 oral vascular lesions treated with the LT using a Nd:YAG laser (1064 nm), including 24 thick lesions treated using a combination of the LT and intralesional photocoagulation. All treatment outcomes were satisfactory without serious complications such as deep ulcer formation, scarring, bleeding, or severe swelling. Laser therapy with the LT is a promising less-invasive treatment for oral vascular lesions.

Angiogenesis in tissue engineering: from concept to the vascularization of scaffold construct

NASA Astrophysics Data System (ADS)

Amirah Ishak, Siti; Pangestu Djuansjah, J. R.; Kadir, M. R. Abdul; Sukmana, Irza

2014-06-01

Angiogenesis, the formation of micro-vascular network from the preexisting vascular vessels, has been studied in the connection to the normal developmental process as well as numerous diseases. In tissue engineering research, angiogenesis is also essential to promote micro-vascular network inside engineered tissue constructs, mimicking a functional blood vessel in vivo. Micro-vascular network can be used to maintain adequate tissue oxygenation, nutrient transfer and waste removal. One of the problems faced by angiogenesis researchers is to find suitable in vitro assays and methods for assessing the effect of regulators on angiogenesis and micro-vessel formation. The assay would be reliable and repeatable with easily quantifiable with physiologically relevant. This review aims to highlights recent advanced and future challenges in developing and using an in vitro angiogenesis assay for the application on biomedical and tissue engineering research.

Vascular Sap Proteomics: Providing Insight into Long-Distance Signaling during Stress

PubMed Central

Carella, Philip; Wilson, Daniel C.; Kempthorne, Christine J.; Cameron, Robin K.

2016-01-01

The plant vascular system, composed of the xylem and phloem, is important for the transport of water, mineral nutrients, and photosynthate throughout the plant body. The vasculature is also the primary means by which developmental and stress signals move from one organ to another. Due to practical and technological limitations, proteomics analysis of xylem and phloem sap has been understudied in comparison to accessible sample types such as leaves and roots. However, recent advances in sample collection techniques and mass spectrometry technology are making it possible to comprehensively analyze vascular sap proteomes. In this mini-review, we discuss the emerging field of vascular sap proteomics, with a focus on recent comparative studies to identify vascular proteins that may play roles in long-distance signaling and other processes during stress responses in plants. PMID:27242852

Fibroblast Growth Factors and Vascular Endothelial Growth Factor Promote Cardiac Reprogramming under Defined Conditions

PubMed Central

Yamakawa, Hiroyuki; Muraoka, Naoto; Miyamoto, Kazutaka; Sadahiro, Taketaro; Isomi, Mari; Haginiwa, Sho; Kojima, Hidenori; Umei, Tomohiko; Akiyama, Mizuha; Kuishi, Yuki; Kurokawa, Junko; Furukawa, Tetsushi; Fukuda, Keiichi; Ieda, Masaki

2015-01-01

Summary Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF) 2, FGF10, and vascular endothelial growth factor (VEGF), termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming. PMID:26626177

Genomic and non-genomic effects of androgens in the cardiovascular system: clinical implications.

PubMed

Lucas-Herald, Angela K; Alves-Lopes, Rheure; Montezano, Augusto C; Ahmed, S Faisal; Touyz, Rhian M

2017-07-01

The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells. Androgens are essential for many developmental and physiological processes, especially in male reproductive tissues. It is now clear that androgens have multiple actions besides sex differentiation and sexual maturation and that many physiological systems are influenced by androgens, including regulation of cardiovascular function [nitric oxide (NO) release, Ca 2+ mobilization, vascular apoptosis, hypertrophy, calcification, senescence and reactive oxygen species (ROS) generation]. This review focuses on evidence indicating that interplay between genomic and non-genomic actions of testosterone may influence cardiovascular function. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Cardiovascular disease in childhood: the role of obesity.

PubMed

Herouvi, Despina; Karanasios, Evangelos; Karayianni, Christina; Karavanaki, Kyriaki

2013-06-01

In recent years, childhood obesity is becoming an epidemic health problem. It is now evident from many studies that childhood obesity is correlated with adult excess weight status and the development of risk factors for cardiovascular diseases in adulthood, including hypertension, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. The exposure to obesity and to the above risk factors during childhood subsequently lead to atherosclerotic development, such as altered vascular structure and function, although the mechanisms are still unclear. Several non-invasive, and thus easy-to-obtain measures of arterial structure and function, have been shown to be clinically useful in providing information about vasculature early in the course of atherosclerosis, including measurement of endothelial function, carotid intima media thickness, and arterial stiffness. The early detection of cardiovascular abnormalities is essential because the control of the atherogenic process is more effective during its early stages. The present review focuses on the cardiovascular consequences of obesity, on the mechanisms and the methods of measurement of endothelial dysfunction in obese children and adolescents, and on the ways of intervention for the improvement of vascular health.

Computational Modeling of 3D Tumor Growth and Angiogenesis for Chemotherapy Evaluation

PubMed Central

Tang, Lei; van de Ven, Anne L.; Guo, Dongmin; Andasari, Vivi; Cristini, Vittorio; Li, King C.; Zhou, Xiaobo

2014-01-01

Solid tumors develop abnormally at spatial and temporal scales, giving rise to biophysical barriers that impact anti-tumor chemotherapy. This may increase the expenditure and time for conventional drug pharmacokinetic and pharmacodynamic studies. In order to facilitate drug discovery, we propose a mathematical model that couples three-dimensional tumor growth and angiogenesis to simulate tumor progression for chemotherapy evaluation. This application-oriented model incorporates complex dynamical processes including cell- and vascular-mediated interstitial pressure, mass transport, angiogenesis, cell proliferation, and vessel maturation to model tumor progression through multiple stages including tumor initiation, avascular growth, and transition from avascular to vascular growth. Compared to pure mechanistic models, the proposed empirical methods are not only easy to conduct but can provide realistic predictions and calculations. A series of computational simulations were conducted to demonstrate the advantages of the proposed comprehensive model. The computational simulation results suggest that solid tumor geometry is related to the interstitial pressure, such that tumors with high interstitial pressure are more likely to develop dendritic structures than those with low interstitial pressure. PMID:24404145

Primary vascularization of allografts governs their immunogenicity and susceptibility to tolerogenesis

PubMed Central

Kant, Cavit D.; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Connolly, Sarah E; Germana, Sharon; Winn, Henry J.; LeGuern, Christian; Tocco, Georges; Benichou, Gilles

2013-01-01

We investigated the influence of allograft primary vascularization on alloimmunity, rejection and tolerance in mice. First, we showed that fully allogeneic primarily vascularized and conventional skin transplants were rejected at the same pace. Remarkably, however, short-term treatment of mice with anti-CD40L antibodies achieved long-term survival of vascularized skin and cardiac transplants but not conventional skin grafts. Non-vascularized skin transplants triggered vigorous direct and indirect pro-inflammatory type 1 T cell responses (IL-2 and γIFN) while primarily-vascularized skin allografts failed to trigger a significant indirect alloresponse. Similar lack of indirect alloreactivity was also observed after placement of different vascularized organ transplants including hearts and kidneys while hearts placed under the skin (non-vascularized) triggers potent indirect alloresponses. Altogether, these results suggest that primary vascularization of allografts is associated with lack of indirect T cell alloreactivity. Finally, we show that long-term survival of vascularized skin allografts induced by anti-CD40L antibodies was associated with a combined lack of indirect alloresponse and a shift of the direct alloresponse towards a type 2 cytokine (IL-4, IL-10) secretion pattern but no activation/expansion of regulatory T cells. Therefore, primary vascularization of allografts governs their immunogenicity and tolerogenicity. PMID:23833234

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement.

PubMed

Sachdev, Perminder; Kalaria, Raj; O'Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan G; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination. Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force. Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized. The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved.

The impact of high-intensity interval training versus moderate-intensity continuous training on vascular function: a systematic review and meta-analysis.

PubMed

Ramos, Joyce S; Dalleck, Lance C; Tjonna, Arnt Erik; Beetham, Kassia S; Coombes, Jeff S

2015-05-01

Vascular dysfunction is a precursor to the atherosclerotic cascade, significantly increasing susceptibility to cardiovascular events such as myocardial infarction or stroke. Previous studies have revealed a strong relationship between vascular function and cardiorespiratory fitness (CRF). Thus, since high-intensity interval training (HIIT) is a potent method of improving CRF, several small randomized trials have investigated the impact on vascular function of HIIT relative to moderate-intensity continuous training (MICT). The aim of this study was to systematically review the evidence and quantify the impact on vascular function of HIIT compared with MICT. Three electronic databases (PubMed, Embase, and MEDLINE) were searched (until May 2014) for randomized trials comparing the effect of at least 2 weeks of HIIT and MICT on vascular function. HIIT protocols involved predominantly aerobic exercise at a high intensity, interspersed with active or passive recovery periods. We performed a meta-analysis to compare the mean difference in the change in vascular function assessed via brachial artery flow-mediated dilation (FMD) from baseline to post-intervention between HIIT and MICT. The impact of HIIT versus MICT on CRF, traditional cardiovascular disease (CVD) risk factors, and biomarkers associated with vascular function (oxidative stress, inflammation, and insulin resistance) was also reviewed across included studies. Seven randomized trials, including 182 patients, met the eligibility criteria and were included in the meta-analysis. A commonly used HIIT prescription was four intervals of 4 min (4 × 4 HIIT) at 85-95% of maximum or peak heart rate (HRmax/peak), interspersed with 3 min of active recovery at 60-70% HRmax/peak, three times per week for 12-16 weeks. Brachial artery FMD improved by 4.31 and 2.15% following HIIT and MICT, respectively. This resulted in a significant (p < 0.05) mean difference of 2.26%. HIIT also had a greater tendency than MICT to induce positive effects on secondary outcome measures, including CRF, traditional CVD risk factors, oxidative stress, inflammation, and insulin sensitivity. HIIT is more effective at improving brachial artery vascular function than MICT, perhaps due to its tendency to positively influence CRF, traditional CVD risk factors, oxidative stress, inflammation, and insulin sensitivity. However, the variability in the secondary outcome measures, coupled with the small sample sizes in these studies, limits this finding. Nonetheless, this review suggests that 4 × 4 HIIT, three times per week for at least 12 weeks, is a powerful form of exercise to enhance vascular function.

Molecular controls of arterial morphogenesis

PubMed Central

Simons, Michael; Eichmann, Anne

2015-01-01

Formation of arterial vasculature, here termed arteriogenesis, is a central process in embryonic vascular development as well as in adult tissues. While the process of capillary formation, angiogenesis, is relatively well understood, much remains to be learned about arteriogenesis. Recent discoveries point to the key role played by vascular endothelial growth factor receptor 2 (VEGFR2) in control of this process and to newly identified control circuits that dramatically influence its activity. The latter can present particularly attractive targets for a new class of therapeutic agents capable of activation of this signaling cascade in a ligand-independent manner, thereby promoting arteriogenesis in diseased tissues. PMID:25953926

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.

Stem Cells on Biomaterials for Synthetic Grafts to Promote Vascular Healing

PubMed Central

Babczyk, Patrick; Conzendorf, Clelia; Klose, Jens; Schulze, Margit; Harre, Kathrin; Tobiasch, Edda

2014-01-01

This review is divided into two interconnected parts, namely a biological and a chemical one. The focus of the first part is on the biological background for constructing tissue-engineered vascular grafts to promote vascular healing. Various cell types, such as embryonic, mesenchymal and induced pluripotent stem cells, progenitor cells and endothelial- and smooth muscle cells will be discussed with respect to their specific markers. The in vitro and in vivo models and their potential to treat vascular diseases are also introduced. The chemical part focuses on strategies using either artificial or natural polymers for scaffold fabrication, including decellularized cardiovascular tissue. An overview will be given on scaffold fabrication including conventional methods and nanotechnologies. Special attention is given to 3D network formation via different chemical and physical cross-linking methods. In particular, electron beam treatment is introduced as a method to combine 3D network formation and surface modification. The review includes recently published scientific data and patents which have been registered within the last decade. PMID:26237251

Prospects for Vascular Access Education in Developing Countries: Current Situation in Cambodia.

PubMed

Naganuma, Toshihide; Takemoto, Yoshiaki

2017-01-01

We report our activities training doctors on vascular access procedures at International University (IU) Hospital in Cambodia through a program facilitated by Ubiquitous Blood Purification International, a nonprofit organization that provides medical support to developing countries in the field of dialysis medicine. Six doctors from Japan have been involved in the education of medical personnel at IU, and we have collectively visited Cambodia about 15 times from 2010 to 2016. In these visits, we have performed many operations, including 42 for arteriovenous fistula, 1 arteriovenous graft, and 1 percutaneous transluminal angioplasty. Stable development and management of vascular access is increasingly required in Cambodia due to increased use of dialysis therapy, and training of doctors in this technique is urgently required. However, we have encountered several difficulties that need to be addressed, including (1) the situation of personnel receiving this training, (2) problems with facilities, including medical equipment and drugs, (3) financial limitations, and (4) problems with management of vascular access. © 2017 S. Karger AG, Basel.

An optical approach for non-invasive blood clot testing

NASA Astrophysics Data System (ADS)

Kalchenko, Vyacheslav; Brill, Alexander; Fine, Ilya; Harmelin, Alon

2007-02-01

Physiological blood coagulation is an essential biological process. Current tests for plasma coagulation (clotting) need to be performed ex vivo and require fresh blood sampling for every test. A recently published work describes a new, noninvasive, in vivo approach to assess blood coagulation status during mechanical occlusion1. For this purpose, we have tested this approach and applied a controlled laser beam to blood micro-vessels of the mouse ear during mechanical occlusion. Standard setup for intravital transillumination videomicroscopy and laser based imaging techniques were used for monitoring the blood clotting process. Temporal mechanical occlusion of blood vessels in the observed area was applied to ensure blood flow cessation. Subsequently, laser irradiation was used to induce vascular micro-injury. Changes in the vessel wall, as well as in the pattern of blood flow, predispose the area to vascular thrombosis, according to the paradigm of Virchow's triad. In our experiments, two elements of Virchow's triad were used to induce the process of clotting in vivo, and to assess it optically. We identified several parameters that can serve as markers of the blood clotting process in vivo. These include changes in light absorption in the area of illumination, as well as changes in the pattern of the red blood cells' micro-movement in the vessels where blood flow is completely arrested. Thus, our results indicate that blood coagulation status can be characterized by non-invasive, in vivo methodologies.

PO-60 - Renal tumors with extensive vascular disease: management challenges in a pediatric series from the Hospital for Sick Children.

PubMed

Zamperlini-Netto, G; Zanette, A; Wehbi, E; Williams, S; Grant, R M; Brandao, L R

2016-04-01

Venous thrombotic events (VTE) are becoming more and more common in children, particularly in the hospital setting. To date, 1 in 200 children admitted to tertiary pediatric hospitals are now being recognized to develop VTE. Amongst those patients with an identified thrombotic occlusion, pediatric patients diagnosed with renal tumors have long been recognized, but their ideal management in the instances of vascular invasion remains controversial. We describe the clinical behavior of patients diagnosed with renal tumors and extra renal vascular involvement at The Hospital for Sick Children in Toronto, Canada. A retrospective analysis was conducted in patients diagnosed from 1990 to 2012. Data collected included: age, gender, symptoms at presentation, staging, pathology report, radiological evidence of intravascular thrombus [i.e. renal veins (RV), inferior vena cava (IVC) and right atrium (RA)], intraoperative findings, therapeutic protocol implemented and anticoagulation; for outcomes, tumor and/or thrombus recurrence, thromboembolic phenomena [i.e. pulmonary embolism (PE)] and survival. Of 299 patients with renal tumors identified, 292 were included: Wilms (219), Renal Cell Carcinoma (RCC, 29), Clear Cell Sarcoma of the Kidney (CCSK, 12), others (32). The median age of the group was 4.53years (4days - 18 years). Extra renal vascular disease was identified in 29 patients, with a median age 7.05years (0.6-16 years; p=0.03), including Wilms tumors (22/219, 10%), RCC (2/29, 7%), CCSK (1/12, 8.3%) and others (4/32, 12.5%; p=0.01). Vascular involvement comprised exclusive evidence of RV disease (7), IVC disease (19; 15 infra-hepatic), RA disease (3) and PE (5).Treatment escalation because of vascular disease included neo-adjuvant chemotherapy (12; Wilms [11], RCC [1]), intraoperative cavectomy/ thrombectomy (1; Wilms), and cavotomies (11 Wilms [7], RCC [1], CCSK [1], PNET [1], sarcoma [1]). Four patients were placed under cardiopulmonary bypass. Anticoagulation was administered in 9/29 patients for their tumor-related thrombus, and one had a minor bleeding complications (oozing from the central venous line insertion site). Renal tumors with vascular invasion are a rare and challenging entity. Treatment included mostly cancer-related therapies and the role of vascular surgical approaches and/or systemic anticoagulation remains to be clarified. © 2016 Elsevier Ltd. All rights reserved.

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.

Oxidative stress as a mechanism of added sugar-induced cardiovascular disease.

PubMed

Prasad, Kailash; Dhar, Indu

2014-12-01

Added sugars comprising of table sugar, brown sugar, corn syrup, maple syrup, honey, molasses, and other sweeteners in the prepared processed foods and beverages have been implicated in the pathophysiology of cardiovascular diseases. This article deals with the reactive oxygen species (ROS) as a mechanism of sugar-induced cardiovascular diseases. There is an association between the consumption of high levels of serum glucose with cardiovascular diseases. Various sources of sugar-induced generation of ROS, including mitochondria, nicotinamide adenine dinucleotide phosphate-oxidase, advanced glycation end products, insulin, and uric acid have been discussed. The mechanism by which ROS induce the development of atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias have been discussed in detail. In conclusion, the data suggest that added sugars induce atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias and that these effects of added sugars are mediated through ROS.

Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart.

PubMed

Abdul-Ghani, Mohammad; Suen, Colin; Jiang, Baohua; Deng, Yupu; Weldrick, Jonathan J; Putinski, Charis; Brunette, Steve; Fernando, Pasan; Lee, Tom T; Flynn, Peter; Leenen, Frans H H; Burgon, Patrick G; Stewart, Duncan J; Megeney, Lynn A

2017-10-01

The post-natal heart adapts to stress and overload through hypertrophic growth, a process that may be pathologic or beneficial (physiologic hypertrophy). Physiologic hypertrophy improves cardiac performance in both healthy and diseased individuals, yet the mechanisms that propagate this favorable adaptation remain poorly defined. We identify the cytokine cardiotrophin 1 (CT1) as a factor capable of recapitulating the key features of physiologic growth of the heart including transient and reversible hypertrophy of the myocardium, and stimulation of cardiomyocyte-derived angiogenic signals leading to increased vascularity. The capacity of CT1 to induce physiologic hypertrophy originates from a CK2-mediated restraining of caspase activation, preventing the transition to unrestrained pathologic growth. Exogenous CT1 protein delivery attenuated pathology and restored contractile function in a severe model of right heart failure, suggesting a novel treatment option for this intractable cardiac disease.

Management of war-related vascular injuries: experience from the second gulf war.

PubMed

Jawas, Ali; Abbas, Alaa K; Nazzal, Munier; Albader, Marzoog; Abu-Zidan, Fikri M

2013-07-01

To study the biomechanism, pattern of injury, management, and outcome of major vascular injuries treated at Mubarak Al-Kabeer Teaching Hospital, Kuwait during the Second Gulf War. This is a descriptive retrospective study. War-related injured patients who had major vascular injuries and were treated at Mubarak Al-Kabeer Teaching Hospital from August 1990 to September 1991 were studied. Studied variables included age, gender, anatomical site of vascular injury, mechanism of injury, associated injuries, type of vascular repair, and clinical outcome. 36 patients having a mean (SD) age of 29.8 (10.2) years were studied. 32 (89%) were males and 21 (58%) were civilians. Majority of injuries were caused by bullets (47.2%) and blast injuries (47.2%). Eight patients (22%) presented with shock.There were 31 arterial injuries, common and superficial femoral artery injuries were most common (10/31). Arterial repair included interposition saphenous vein graft in seven patients, thrombectomy with end-to-end / lateral repair in twelve patients, vein patch in two patients, and arterial ligation in four patients. Six patients had arterial ligation as part of primary amputation. 3/21 (14.3%) patients had secondary amputation after attempted arterial vascular repair of an extremity. There were a total of 17 venous injuries, 13 managed by lateral suture repair and 4 by ligation. The median (range) hospital stay was 8 (1-76) days. 5 patients died (14%). Major vascular injuries occurred in 10% of hospitalized war-related injured patients. Our secondary amputation rate of extremities was 14%. The presence of a vascular surgeon within a military surgical team is highly recommended. Basic principles and techniques of vascular repair remain an essential part of training general surgeons because it may be needed in unexpected wars.

Lifestyle and metabolic approaches to maximizing erectile and vascular health.

PubMed

Meldrum, D R; Gambone, J C; Morris, M A; Esposito, K; Giugliano, D; Ignarro, L J

2012-01-01

Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity.

Management of traumatic popliteal vascular injuries in a level I trauma center: A 6-year experience.

PubMed

Sciarretta, Jason D; Macedo, Francisco Igor B; Otero, Christian A; Figueroa, Jose N; Pizano, Louis R; Namias, Nicholas

2015-06-01

Popliteal vascular trauma remains a challenging entity, and carries the greatest risk of limb loss among the lower extremity vascular injuries. Operative management of traumatic popliteal vascular injuries continues to evolve. We aim at describing our experience with such complex injuries, with associated patterns of injury, diagnostic and therapeutic challenges, and outcomes. From January 2006 to September 2011, 191 adult trauma patients presented to an urban level I trauma center in Miami, Florida with traumatic lower extremity vascular injuries. Variables collected included age, gender, mechanism of injury, and clinical status at presentation. Surgical data included vessel injury, technical aspects of repair, associated complications and outcomes. Forty-seven (24.6%) patients were diagnosed with traumatic popliteal vascular injuries. Mean age was 38.1 ± 16.1 years, and the majority of patients were males (43 patients, 91.4%). There were 21 (44.7%) penetrating injuries, and 26 (55.3%) blunt injuries. Vascular repair with saphenous venous interposition graft and PTFE (polytetrafluoroethylene) grafting were performed in 36 (70.7%) and 2 (3.9%) patients, respectively. Blunt popliteal injuries were significantly more associated with major tissue loss, and length of hospital and intensive care unit (ICU) stays. The risk for amputation is increased with longer ICU stays and the use of PTFE grafting for vascular repair. The overall mortality rate in this series was 8.5%. Blunt popliteal vascular injuries are associated with increased morbidity compared to penetrating trauma. Early restoration of blood perfusion, frequent use of interposition grafts with autogenous saphenous vein, and liberal use of fasciotomies play important role to achieve acceptable outcomes. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Vascular Repair After Menstruation Involves Regulation of Vascular Endothelial Growth Factor-Receptor Phosphorylation by sFLT-1

PubMed Central

Graubert, Michael D.; Asuncion Ortega, Maria; Kessel, Bruce; Mortola, Joseph F.; Iruela-Arispe, M. Luisa

2001-01-01

Regeneration of the endometrium after menstruation requires a rapid and highly organized vascular response. Potential regulators of this process include members of the vascular endothelial growth factor (VEGF) family of proteins and their receptors. Although VEGF expression has been detected in the endometrium, the relationship between VEGF production, receptor activation, and endothelial cell proliferation during the endometrial cycle is poorly understood. To better ascertain the relevance of VEGF family members during postmenstrual repair, we have evaluated ligands, receptors, and activity by receptor phosphorylation in human endometrium throughout the menstrual cycle. We found that VEGF is significantly increased at the onset of menstruation, a result of the additive effects of hypoxia, transforming growth factor-α, and interleukin-1β. Both VEGF receptors, FLT-1 and KDR, followed a similar pattern. However, functional activity of KDR, as determined by phosphorylation studies, revealed activation in the late menstrual and early proliferative phases. The degree of KDR phosphorylation was inversely correlated with the presence of sFLT-1. Endothelial cell proliferation analysis in endometrium showed a peak during the late menstrual and early proliferative phases in concert with the presence of VEGF, VEGF receptor phosphorylation, and decrease of sFLT-1. Together, these results suggest that VEGF receptor activation and the subsequent modulation of sFLT-1 in the late menstrual phase likely contributes to the onset of angiogenesis and endothelial repair in the human endometrium. PMID:11290558

Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: a new hypothesis of a possible mechanism of cancer pathogenesis.

PubMed

Karseladze, A I

2015-06-01

To study the peculiarities of vascularization at the stromal-epithelial interface in different types of epithelia and their alterations in precancerous lesions. Peritumoral tissues of 310 patients, tissues of 180 healthy persons and of 50 human embryos and fetuses were used. Traditional histological as well as immunohistochemical methods have been used. The study reveals that the occurrence of blood capillaries in surface squamous epithelium is an ordinary event, both in healthy persons and in peritumoral regions of the patients with squamous cell carcinoma. Glandular epithelial coverings, as well as transitional epithelium, do not contain blood vessels. In squamous epithelium, only basal cells are in contact with the membrane and underlying stroma, the cells of the upper layer receiving nutrients through diffusion. Thus, the cells of squamous epithelium are more vulnerable to blood deficiency, since for instance in the pseudo-multilayered respiratory epithelium each cell is attached directly to the basal membrane and has more ample access to the blood supply. Metaplastic squamous epithelium has a markedly reduced vascularization and seems to be more sensitive to carcinogenic stimuli. High-grade dysplastic squamous epithelium and carcinoma in situ do not contain blood vessels. The process of redistribution of vascular network occurring at the interface of epithelial-stromal frontier plays an important role in maintaining the adequate metabolism of cells including those of epithelial covering. Impairment of this mechanism most probably promotes precancerous alterations.

Paracrine control of vascularization and neurogenesis by neurotrophins.

PubMed

Emanueli, Costanza; Schratzberger, Peter; Kirchmair, Rudolf; Madeddu, Paolo

2003-10-01

The neuronal system plays a fundamental role in the maturation of primitive embryonic vascular network by providing a paracrine template for blood vessel branching and arterial differentiation. Furthermore, postnatal vascular and neural regeneration cooperate in the healing of damaged tissue. Neurogenesis continues in adulthood although confined to specific brain regions. Following ischaemic insult, neural staminal cells contribute towards the healing process through the stimulation of neurogenesis and vasculogenesis. Evidence indicates that nerves and blood vessels exert a reciprocal control of their own growth by paracrine mechanisms. For instance, guidance factors, including vascular endothelial growth factor A (VEGF-A) and semaphorins, which share the ability of binding neuropilin receptors, play a pivotal role in the tridimensional growth pattern of arterial vessels and nerves. Animal models and clinical studies have demonstrated a role of VEGF-A in the pathogenesis of ischaemic and diabetic neuropathies. Further, supplementation with VEGF-A ameliorates neuronal recovery by exerting protective effects on nerves and stimulating reparative neovascularization. Human tissue kallikrein, a recently discovered angiogenic and arteriogenic factor, accelerates neuronal recovery by stimulating the growth of vasa nervorum. Conversely, the neurotrophin nerve growth factor, known to regulate neuronal survival and differentiation, is now regarded as a stimulator of angiogenesis and arteriogenesis. These results indicate that angiogenesis and neurogenesis are paracrinally regulated by growth factors released by endothelial cells and neurons. Supplementation of these growth factors, alone or in combination, could benefit the treatment of ischaemic diseases and neuropathies.

Vascular depression consensus report - a critical update.

PubMed

Aizenstein, Howard J; Baskys, Andrius; Boldrini, Maura; Butters, Meryl A; Diniz, Breno S; Jaiswal, Manoj Kumar; Jellinger, Kurt A; Kruglov, Lev S; Meshandin, Ivan A; Mijajlovic, Milija D; Niklewski, Guenter; Pospos, Sarah; Raju, Keerthy; Richter, Kneginja; Steffens, David C; Taylor, Warren D; Tene, Oren

2016-11-03

Vascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5 th edition - a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term "MRI-defined vascular depression". This diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal-subcortical-limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed. The multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical, intra vitam structural and functional MRI as well as postmortem MRI and neuropathological studies in order to confirm the relationship between clinical symptomatology and changes in specific brain regions related to depression. To elucidate the causal relationship between regional vascular brain changes and vascular depression, animal models could be helpful. Current treatment options include a combination of vasoactive drugs and antidepressants, but the outcomes are still unsatisfying.

Physical examination of the hand.

PubMed

Kenney, Raymond J; Hammert, Warren C

2014-11-01

Examination of the hand is an essential piece of a hand surgeon's skill set. This current concepts review presents a systematic process of performing a comprehensive physical examination of the hand including vascular, sensory, and motor assessments. Evaluations focused on specific hand diseases and injuries are also discussed. This information can be useful for any health care provider treating patients with hand conditions. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Measures of total stress-induced blood pressure responses are associated with vascular damage.

PubMed

Nazzaro, Pietro; Seccia, Teresa; Vulpis, Vito; Schirosi, Gabriella; Serio, Gabriella; Battista, Loredana; Pirrelli, Anna

2005-09-01

The role of cardiovascular reactivity to study hypertension, and the assessment methods, are still controversial. We aimed to verify the association of hypertension and vascular damage with several measures of cardiovascular response. We studied 40 patients with normal-high (132 +/- 1/87 +/- 1 mm Hg) blood pressure (Group 1) and 80 untreated hypertensive subjects. Postischemic forearm vascular resistance (mFVR) served to differentiate hypertensive subjects (142 +/- 2/92 +/- 1 mm Hg v 143 +/- 2/94 +/- 2 mm Hg, P = NS) with a lower (Group 2) and higher (Group 3) hemodynamic index of vascular damage (4.8 +/- .05 v 6.3 +/- .09, P < .001). Reactivity was induced by Stroop (5') and cold pressor (90") tests. We measured muscular contraction and skin conductance as indices of emotional arousal, blood pressure, heart rate, forearm blood flow, and vascular resistance. Reactivity measures included: a) change from baseline, b) residualized score, c) cumulative change from baseline and residualized score, and d) total reactivity as area-under-the-curve (AUC), including changes occurring during baseline and recovery phases. The AUC of systolic blood pressure, diastolic blood pressure, and mFVR progressively increased in the groups (P < .001). Corrections of anthropometric and metabolic confounders were introduced in the Pearson equation between mFVR and reactivity measures. The AUC of SBP, DBP, and forearm blood flow and resistance demonstrated the highest (P < .001) correlation. On multiple regression analysis, AUC of SBP (beta = 0.634) and forearm blood flow (beta = -0.337) were predictive (P < .001) of vascular damage. Total blood pressure stress response, as AUC, including baseline and recovery phases, was significantly better associated with hypertension and vascular damage than the other reactivity measures studied.

NASAs VESGEN: Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways Using GeneLab.

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia A.; Weitzel, Alexander; Vyas, Ruchi J.; Murray, Matthew C.; Wyatt, Sarah E.

2016-01-01

One fundamental requirement shared by humans with all higher terrestrial life forms, including insect wings, higher land plants and other vertebrates, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. One unifying perspective is that vascular patterning offers a useful readout that necessarily integrates complex molecular signaling pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, stress response, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascular-related changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the Euclidean and dynamic dimensions (x,y,t) of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions (i,j,k,...). Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a Notch antagonist were analyzed by VESGEN. Other VESGEN research applications include the mouse retina, GI and coronary vessels, avian placental analogs and translational studies in the astronaut retina related to health challenges for long-duration missions.

Characterisation of calcium phosphate crystals on calcified human aortic vascular smooth muscle cells and potential role of magnesium.

PubMed

Louvet, Loïc; Bazin, Dominique; Büchel, Janine; Steppan, Sonja; Passlick-Deetjen, Jutta; Massy, Ziad A

2015-01-01

Cardiovascular disease including vascular calcification (VC) remains the leading cause of death in patients suffering from chronic kidney disease (CKD). The process of VC seems likely to be a tightly regulated process where vascular smooth muscle cells are playing a key role rather than just a mere passive precipitation of calcium phosphate. Characterisation of the chemical and crystalline structure of VC was mainly led in patients or animal models with CKD. Likewise, Mg2+ was found to be protective in living cells although a potential role for Mg2+ could not be excluded on crystal formation and precipitation. In this study, the crystal formation and the role of Mg2+ were investigated in an in vitro model of primary human aortic vascular smooth muscle cells (HAVSMC) with physical techniques. In HAVSMC incubated with increased Ca x Pi medium, only calcium phosphate apatite crystals (CPA) were detected by Micro-Fourier Transform InfraRed spectroscopy (µFTIR) and Field Effect Scanning Electron Microscope (FE-SEM) and Energy Dispersive X-ray spectrometry (EDX) at the cell layer level. Supplementation with Mg2+ did not alter the crystal composition or structure. The crystal deposition was preferentially positioned near or directly on cells as pictured by FE-SEM observations and EDX measurements. Large µFTIR maps revealed spots of CPA crystals that were associated to the cellular layout. This qualitative analysis suggests a potential beneficial effect of Mg2+ at 5 mM in noticeably reducing the number and intensities of CPA µFTIR spots. For the first time in a model of HAVSMC, induced calcification led to the formation of the sole CPA crystals. Our data seems to exclude a physicochemical role of Mg2+ in altering the CPA crystal growth, composition or structure. Furthermore, Mg2+ beneficial role in attenuating VC should be linked to an active cellular role.

Characterisation of Calcium Phosphate Crystals on Calcified Human Aortic Vascular Smooth Muscle Cells and Potential Role of Magnesium

PubMed Central

Louvet, Loïc; Bazin, Dominique; Büchel, Janine; Steppan, Sonja; Passlick-Deetjen, Jutta; Massy, Ziad A.

2015-01-01

Background Cardiovascular disease including vascular calcification (VC) remains the leading cause of death in patients suffering from chronic kidney disease (CKD). The process of VC seems likely to be a tightly regulated process where vascular smooth muscle cells are playing a key role rather than just a mere passive precipitation of calcium phosphate. Characterisation of the chemical and crystalline structure of VC was mainly led in patients or animal models with CKD. Likewise, Mg2+ was found to be protective in living cells although a potential role for Mg2+ could not be excluded on crystal formation and precipitation. In this study, the crystal formation and the role of Mg2+ were investigated in an in vitro model of primary human aortic vascular smooth muscle cells (HAVSMC) with physical techniques. Methodology/Principal Findings In HAVSMC incubated with increased Ca x Pi medium, only calcium phosphate apatite crystals (CPA) were detected by Micro-Fourier Transform InfraRed spectroscopy (µFTIR) and Field Effect Scanning Electron Microscope (FE — SEM) and Energy Dispersive X-ray spectrometry (EDX) at the cell layer level. Supplementation with Mg2+ did not alter the crystal composition or structure. The crystal deposition was preferentially positioned near or directly on cells as pictured by FE — SEM observations and EDX measurements. Large µFTIR maps revealed spots of CPA crystals that were associated to the cellular layout. This qualitative analysis suggests a potential beneficial effect of Mg2+ at 5 mM in noticeably reducing the number and intensities of CPA µFTIR spots. Conclusions/Significance For the first time in a model of HAVSMC, induced calcification led to the formation of the sole CPA crystals. Our data seems to exclude a physicochemical role of Mg2+ in altering the CPA crystal growth, composition or structure. Furthermore, Mg2+ beneficial role in attenuating VC should be linked to an active cellular role. PMID:25607936

Bmp2 conditional knockout in osteoblasts and endothelial cells does not impair bone formation after injury or mechanical loading in adult mice

PubMed Central

McKenzie, Jennifer A.; Buettmann, Evan G.; Gardner, Michael J.; Silva, Matthew J.

2015-01-01

Post-natal osteogenesis after mechanical trauma or stimulus occurs through either endochondral healing, intramembranous healing or lamellar bone formation. Bone morphogenetic protein 2 (BMP2) is up-regulated in each of these osteogenic processes and is expressed by a variety of cells including osteoblasts and vascular cells. It is known that genetic knockout of Bmp2 in all cells or in osteo-chondroprogenitor cells completely abrogates endochondral healing after full fracture. However, the importance of BMP2 from differentiated osteoblasts and endothelial cells is not known. Moreover, the importance of BMP2 in non-endochondral bone formation such as intramembranous healing or lamellar bone formation is not known. Using inducible and tissue-specific Cre-lox mediated targeting of Bmp2 in adult (10–24 week old) mice, we assessed the role of BMP2 expression globally, by osteoblasts, and by vascular endothelial cells in endochondral healing, intramembranous healing and lamellar bone formation. These three osteogenic processes were modeled using full femur fracture, ulnar stress fracture, and ulnar non-damaging cyclic loading, respectively. Our results confirmed the requirement of BMP2 for endochondral fracture healing, as mice in which Bmp2 was knocked out in all cells prior to fracture failed to form a callus. Targeted deletion of Bmp2 in osteoblasts (osterix-expressing) or vascular endothelial cells (vascular endothelial cadherin-expressing) did not impact fracture healing in any way. Regarding non-endochondral bone formation, we found that BMP2 is largely dispensable for intramembranous bone formation after stress fracture and also not required for lamellar bone formation induced by mechanical loading. Taken together our results indicate that osteoblasts and endothelial cells are not a critical source of BMP2 in endochondral fracture healing, and that non-endochondral bone formation in the adult mouse is not as critically dependent on BMP2. PMID:26344756

Macrophage Migration Inhibitory Factor-Induced Autophagy Contributes to Thrombin-Triggered Endothelial Hyperpermeability in Sepsis.

PubMed

Chao, Chiao-Hsuan; Chen, Hong-Ru; Chuang, Yung-Chun; Yeh, Trai-Ming

2018-07-01

Vascular leakage contributes to the high morbidity and mortality associated with sepsis. Exposure of the endothelium to inflammatory mediators, such as thrombin and cytokines, during sepsis leads to hyperpermeability. We recently observed that autophagy, a cellular process for protein turnover, is involved in macrophage migration inhibitory factor (MIF)-induced endothelial hyperpermeability. Even though it is known that thrombin induces endothelial cells to secrete MIF and to increase vascular permeability, the possible role of autophagy in this process is unknown. In this study, we proposed and tested the hypothesis that MIF-induced autophagy plays an important role in thrombin-induced endothelial hyperpermeability. We evaluated the effects of thrombin on endothelial permeability, autophagy induction, and MIF secretion in vitro using the human microvascular endothelial cell line-1 and human umbilical vein endothelial cells. Several mechanisms/read outs of endothelial permeability and autophagy formation were examined. We observed that blocking autophagy attenuated thrombin-induced endothelial hyperpermeability. Furthermore, thrombin-induced MIF secretion was involved in this process because MIF inhibition reduced thrombin-induced autophagy and hyperpermeability. Finally, we showed that blocking MIF or autophagy effectively alleviated vascular leakage and mortality in endotoxemic mice. Thus, MIF-induced autophagy may represent a common mechanism causing vascular leakage in sepsis.

Quality assurance of lower limb venous duplex scans performed by vascular surgeons.

PubMed

Kordowicz, A; Ferguson, G; Salaman, R; Onwudike, M

2015-02-01

Duplex scanning is the gold standard for investigating venous reflux; increasingly surgeons perform these scans themselves. There has been no data published analysing the accuracy of Duplex scans performed by vascular surgeons. We aimed to evaluate an objective method of comparing the results of lower limb Duplex scans performed by one consultant vascular surgeon with those performed by a vascular technologist. We assessed 100 legs with symptomatic varicose veins. Each patient underwent two lower limb venous Duplex scans; one performed by a consultant vascular surgeon and one by a vascular technologist. Scan results were randomised and sent to two consultant vascular surgeons blinded to the identity and experience of the sonographer. They were asked to recommend treatment. A k score was calculated in each case to assess the level of agreement between the scans performed by the consultant and the technologist. Eighty-one patients were studied (53 females). The kappa score for assessor 1 was 0.60 (95%CI:0.44-0.75) and for assessor 2 was 0.62 (95%CI:0.48-0.75). k scores >0.60 represent a substantial strength of agreement. Duplex scans performed by this surgeon were comparable to those performed by a vascular technologist. It is possible to quality-assure duplex performed by vascular surgeons without directly observing the scanning process or reviewing digitally recorded images. We propose standardisation of training, assessment and quality assurance for vascular surgeons wishing to perform ultrasound scans.

Generating favorable growth factor and protease release profiles to enable extracellular matrix accumulation within an in vitro tissue engineering environment.

PubMed

Zhang, Xiaoqing; Battiston, Kyle G; Labow, Rosalind S; Simmons, Craig A; Santerre, J Paul

2017-05-01

Tissue engineering (particularly for the case of load-bearing cardiovascular and connective tissues) requires the ability to promote the production and accumulation of extracellular matrix (ECM) components (e.g., collagen, glycosaminoglycan and elastin). Although different approaches have been attempted in order to enhance ECM accumulation in tissue engineered constructs, studies of underlying signalling mechanisms that influence ECM deposition and degradation during tissue remodelling and regeneration in multi-cellular culture systems have been limited. The current study investigated vascular smooth muscle cell (VSMC)-monocyte co-culture systems using different VSMC:monocyte ratios, within a degradable polyurethane scaffold, to assess their influence on ECM generation and degradation processes, and to elucidate relevant signalling molecules involved in this in vitro vascular tissue engineering system. It was found that a desired release profile of growth factors (e.g. insulin growth factor-1 (IGF-1)) and hydrolytic proteases (e.g. matrix-metalloproteinases 2, 9, 13 and 14 (MMP2, MMP9, MMP13 and MMP14)), could be achieved in co-culture systems, yielding an accumulation of ECM (specifically for 2:1 and 4:1 VSMC:monocyte culture systems). This study has significant implications for the tissue engineering field (including vascular tissue engineering), not only because it identified important cytokines and proteases that control ECM accumulation/degradation within synthetic tissue engineering scaffolds, but also because the established culture systems could be applied to improve the development of different types of tissue constructs. Sufficient extracellular matrix accumulation within cardiovascular and connective tissue engineered constructs is a prerequisite for their appropriate function in vivo. This study established co-culture systems with tissue specific cells (vascular smooth muscle cells (VSMCs)) and defined ratios of immune cells (monocytes) to investigate extracellular matrix (ECM) generation and degradation processes, revealing important mechanisms underlying ECM turnover during vascular tissue regeneration/remodelling. A specific growth factor (IGF-1), as well as hydrolytic proteases (e.g. MMP2, MMP9, MMP13 and MMP14), were identified as playing important roles in these processes. ECM accumulation was found to be dependent on achieving a desired release profile of these ECM-promoting and ECM-degrading factors within the multi-cellular microenvironment. The findings enhance our understanding of ECM deposition and degradation during in vitro tissue engineering and would be applicable to the repair or regeneration of a variety of tissues. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The Celution® System: Automated Processing of Adipose-Derived Regenerative Cells in a Functionally Closed System

PubMed Central

Fraser, John K.; Hicok, Kevin C.; Shanahan, Rob; Zhu, Min; Miller, Scott; Arm, Douglas M.

2014-01-01

Objective: To develop a closed, automated system that standardizes the processing of human adipose tissue to obtain and concentrate regenerative cells suitable for clinical treatment of thermal and radioactive burn wounds. Approach: A medical device was designed to automate processing of adipose tissue to obtain a clinical-grade cell output of stromal vascular cells that may be used immediately as a therapy for a number of conditions, including nonhealing wounds resulting from radiation damage. Results: The Celution® System reliably and reproducibly generated adipose-derived regenerative cells (ADRCs) from tissue collected manually and from three commercial power-assisted liposuction devices. The entire process of introducing tissue into the system, tissue washing and proteolytic digestion, isolation and concentration of the nonadipocyte nucleated cell fraction, and return to the patient as a wound therapeutic, can be achieved in approximately 1.5 h. An alternative approach that applies ultrasound energy in place of enzymatic digestion demonstrates extremely poor efficiency cell extraction. Innovation: The Celution System is the first medical device validated and approved by multiple international regulatory authorities to generate autologous stromal vascular cells from adipose tissue that can be used in a real-time bedside manner. Conclusion: Initial preclinical and clinical studies using ADRCs obtained using the automated tissue processing Celution device described herein validate a safe and effective manner to obtain a promising novel cell-based treatment for wound healing. PMID:24761343

Whole Organ Tissue Vascularization: Engineering the Tree to Develop the Fruits.

PubMed

Pellegata, Alessandro F; Tedeschi, Alfonso M; De Coppi, Paolo

2018-01-01

Tissue engineering aims to regenerate and recapitulate a tissue or organ that has lost its function. So far successful clinical translation has been limited to hollow organs in which rudimental vascularization can be achieved by inserting the graft into flaps of the omentum or muscle fascia. This technique used to stimulate vascularization of the graft takes advantage of angiogenesis from existing vascular networks. Vascularization of the engineered graft is a fundamental requirement in the process of engineering more complex organs, as it is crucial for the efficient delivery of nutrients and oxygen following in-vivo implantation. To achieve vascularization of the organ many different techniques have been investigated and exploited. The most promising results have been obtained by seeding endothelial cells directly into decellularized scaffolds, taking advantage of the channels remaining from the pre-existing vascular network. Currently, the main hurdle we need to overcome is achieving a fully functional vascular endothelium, stable over a long time period of time, which is engineered using a cell source that is clinically suitable and can generate, in vitro , a yield of cells suitable for the engineering of human sized organs. This review will give an overview of the approaches that have recently been investigated to address the issue of vascularization in the field of tissue engineering of whole organs, and will highlight the current caveats and hurdles that should be addressed in the future.

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.

Non-invasive vascular biomarkers in patients with Behçet's disease: review of the data and future perspectives.

PubMed

Protogerou, Athanase D; Nasothimiou, Efthimia G; Sfikakis, Petros P; Tzioufas, Athanasios G

2017-01-01

Vascular inflammation in small to large veins and arteries contributes substantially to mortality above that of the general population in Behçet's disease. Recent data verified also the presence of accelerated classical subclinical arterial damage (atheromatosis, arteriosclerosis, arterial hypertrophy) even in patients free of overt vascular complications, and may be complementary to that of vasculitis. Early detection of such vascular damage might provide helpful pathophysiological insight and potentially even guide treatment management. Herein, we review the existing literature for each one of the most widely applied non-invasive vascular biomarkers (assessing endothelial dysfunction, atheromatosis/hypertrophy, arteriosclerosis and central haemodynamic parameters) that are clinically used in primary cardiovascular prevention. We aim to: (i) identify early pathophysiological vascular pathways, complementary to vasculitis, in the development of vascular complications and (ii) identify gaps in knowledge and suggest future research topics. We identified evidence of proof of concept for some of the widely applied non-invasive vascular biomarkers (carotid plaques, pulse wave velocity, flow mediated dilatation). Yet, several steps in their clinical validation process are lacking. Extensive vascular phenotyping of a large prospective observational patient cohort with the application of these easy-to-use, low-cost, free of any adverse effect, non-invasive methods should be performed in order to test their ability to provide clinically meaningful guidance regarding the prognosis and treatment of Behçet's disease.

Vascular dysfunction and fibrosis in stroke-prone spontaneously hypertensive rats: The aldosterone-mineralocorticoid receptor-Nox1 axis.

PubMed

Harvey, Adam P; Montezano, Augusto C; Hood, Katie Y; Lopes, Rheure A; Rios, Francisco; Ceravolo, Graziela; Graham, Delyth; Touyz, Rhian M

2017-06-15

We questioned whether aldosterone and oxidative stress play a role in vascular damage in severe hypertension and investigated the role of Nox1 in this process. We studied mesenteric arteries, aortas and vascular smooth muscle cells (VSMC) from WKY and SHRSP rats. Vascular effects of eplerenone or canrenoic acid (CA) (mineralocorticoid receptor (MR) blockers), ML171 (Nox1 inhibitor) and EHT1864 (Rac1/2 inhibitor) were assessed. Nox1-knockout mice were also studied. Vessels and VSMCs were probed for Noxs, reactive oxygen species (ROS) and pro-fibrotic/inflammatory signaling. Blood pressure and plasma levels of aldosterone and galectin-3 were increased in SHRSP versus WKY. Acetylcholine-induced vasorelaxation was decreased (61% vs 115%) and phenylephrine-induced contraction increased in SHRSP versus WKY (E max 132.8% vs 96.9%, p<0.05). Eplerenone, ML171 and EHT1864 attenuated hypercontractility in SHRSP. Vascular expression of collagen, fibronectin, TGFβ, MCP-1, RANTES, MMP2, MMP9 and p66Shc was increased in SHRSP versus WKY. These changes were associated with increased ROS generation, 3-nitrotyrosine expression and Nox1 upregulation. Activation of vascular p66Shc and increased expression of Nox1 and collagen I were prevented by CA in SHRSP. Nox1 expression was increased in aldosterone-stimulated WKY VSMCs, an effect that was amplified in SHRSP VSMCs (5.2vs9.9 fold-increase). ML171 prevented aldosterone-induced VSMC Nox1-ROS production. Aldosterone increased vascular expression of fibronectin and PAI-1 in wild-type mice but not in Nox1-knockout mice. Our findings suggest that aldosterone, which is increased in SHRSP, induces vascular damage through MR-Nox1-p66Shc-mediated processes that modulate pro-fibrotic and pro-inflammatory signaling pathways. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Engineering clinically relevant volumes of vascularized bone.

PubMed

Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

2015-05-01

Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice.

PubMed

Nishikori, Yoriko; Shiota, Naotaka; Okunishi, Hideki

2014-11-01

Mast cells (MCs) reside in cutaneous tissue, and an increment of MCs is suggested to induce vascular regression in the process of wound healing. To clarify participation of MCs in diabetic cutaneous wound healing, we created an excisional wound on diabetic mice 4 weeks after streptozotocin injections and subsequently investigated the healing processes for 49 days, comparing them with control mice. The rate of wound closure was not markedly different between the diabetic and control mice. In the proliferative phase at days 7 and 14, neovascularization in the wound was weaker in diabetic mice than in control mice. In the remodeling phase at day 21 and afterward, rapid vascular regression occurred in control mice; however, neovascularization was still observed in diabetic mice where the number of vessels in granulation tissues was relatively higher than in control mice. In the remodeling phase of the control mice, MCs within the wound began to increase rapidly and resulted in considerable accumulation, whereas the increment of MCs was delayed in diabetic mice. In addition, the number of fibroblast growth factor (FGF)- or vascular endothelial growth factor (VEGF)-immunopositive hypertrophic fibroblast-like spindle cells and c-Kit-positive/VEGFR2-positive/FcεRIα-negative endothelial progenitor cells (EPCs) were higher in diabetic wounds. In conclusion, neovascularization in the proliferative phase and vascular regression in the remodeling phase were impaired in diabetic mice. The delayed increment of MCs and sustained angiogenic stimuli by fibroblast-like spindle cells and EPCs may inhibit vascular regression in the remodeling phase and impair the wound-healing process in diabetic mice.

Critical Endothelial Regulation by LRP5 during Retinal Vascular Development.

PubMed

Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H; Nagao, Masashi; Warman, Matthew L; Olsen, Bjorn R

2016-01-01

Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature.

Critical Endothelial Regulation by LRP5 during Retinal Vascular Development

PubMed Central

Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H.; Nagao, Masashi; Warman, Matthew L.; Olsen, Bjorn R.

2016-01-01

Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature. PMID:27031698

Forskolin Modifies Retinal Vascular Development in Mrp4-Knockout Mice

PubMed Central

Matsumiya, Wataru; Kusuhara, Sentaro; Hayashibe, Keiko; Maruyama, Kazuichi; Kusuhara, Hiroyuki; Tagami, Mizuki; Schuetz, John D.; Negi, Akira

2012-01-01

Purpose. Multidrug resistance protein 4 (MRP4) effluxes a wide variety of endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is exclusively expressed in vascular endothelial cells (ECs) of the retina. This study aimed to investigate the role of MRP4 in retinal vascular development. Methods. The retinal vascular phenotype of Mrp4−/− mice was examined by whole-mount immunohistochemistry at P3, P6, and P14. The retinas from P6 pups that received an intraperitoneal injection of either solvent control or forskolin, an inducer of intracellular cAMP formation, at P4 and P5 were analyzed in terms of their vascular formation (vascular length, vascular branching, vascular density, and the number of tip cells), cell proliferation and apoptosis, and vessel stability. Results. The Mrp4−/− mice exhibited no overt abnormalities in the development of the retinal vasculature, but retinal vascular development in the Mrp4−/− mice was suppressed in response to forskolin administration. There was a significant decrease in the vascular length, vascular branching, and vascular density, and inhibited tip cell formation at the vascular front. The forskolin-treated Mrp4−/− mice showed an increased number of Ki67-positive and cleaved caspase 3–positive ECs, a significant decrease in the amount of pericyte coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia (75% oxygen) from P7 to P12, the Mrp4−/− mice showed a significant increase in the unvascularized retinal area. Conclusions. Mrp4−/− mice exhibited suppressed retinal vascular development in response to forskolin treatment. Thus, Mrp4 might have protective roles in retinal vascular development by regulating the intracellular cAMP level. PMID:23154460

Forskolin modifies retinal vascular development in Mrp4-knockout mice.

PubMed

Matsumiya, Wataru; Kusuhara, Sentaro; Hayashibe, Keiko; Maruyama, Kazuichi; Kusuhara, Hiroyuki; Tagami, Mizuki; Schuetz, John D; Negi, Akira

2012-12-07

Multidrug resistance protein 4 (MRP4) effluxes a wide variety of endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is exclusively expressed in vascular endothelial cells (ECs) of the retina. This study aimed to investigate the role of MRP4 in retinal vascular development. The retinal vascular phenotype of Mrp4(-/-) mice was examined by whole-mount immunohistochemistry at P3, P6, and P14. The retinas from P6 pups that received an intraperitoneal injection of either solvent control or forskolin, an inducer of intracellular cAMP formation, at P4 and P5 were analyzed in terms of their vascular formation (vascular length, vascular branching, vascular density, and the number of tip cells), cell proliferation and apoptosis, and vessel stability. The Mrp4(-/-) mice exhibited no overt abnormalities in the development of the retinal vasculature, but retinal vascular development in the Mrp4(-/-) mice was suppressed in response to forskolin administration. There was a significant decrease in the vascular length, vascular branching, and vascular density, and inhibited tip cell formation at the vascular front. The forskolin-treated Mrp4(-/-) mice showed an increased number of Ki67-positive and cleaved caspase 3-positive ECs, a significant decrease in the amount of pericyte coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia (75% oxygen) from P7 to P12, the Mrp4(-/-) mice showed a significant increase in the unvascularized retinal area. Mrp4(-/-) mice exhibited suppressed retinal vascular development in response to forskolin treatment. Thus, Mrp4 might have protective roles in retinal vascular development by regulating the intracellular cAMP level.

Asymptomatic cervicocerebral atherosclerosis, intracranial vascular resistance and cognition: the AsIA-neuropsychology study.

PubMed

López-Olóriz, Jorge; López-Cancio, Elena; Arenillas, Juan F; Hernández, María; Jiménez, Marta; Dorado, Laura; Barrios, Maite; Soriano-Raya, Juan José; Miralbell, Júlia; Cáceres, Cynthia; Forés, Rosa; Pera, Guillem; Dávalos, Antoni; Mataró, Maria

2013-10-01

Carotid atherosclerosis has emerged as a relevant contributor to cognitive impairment and dementia whereas the role of intracranial stenosis and vascular resistance in cognition remains unknown. This study aims to assess the association of asymptomatic cervicocerebral atherosclerosis and intracranial vascular resistance with cognitive performance in a large dementia-free population. The Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) Neuropsychology Study included 747 Caucasian subjects older than 50 with a moderate-high vascular risk (assessed by REGICOR score) and without history of neither symptomatic vascular disease nor dementia. Extracranial and transcranial color-coded duplex ultrasound examination was performed to assess carotid intima-media thickness (IMT), presence of carotid plaques (ECAD group), intracranial stenosis (ICAD group), and middle cerebral artery pulsatility index (MCA-PI) as a measure of intracranial vascular resistance. Neuropsychological assessment included tests in three cognitive domains: visuospatial skills and speed, verbal memory and verbal fluency. In univariate analyses, carotid IMT, ECAD and MCA-PI were associated with lower performance in almost all cognitive domains, and ICAD was associated with poor performance in some visuospatial and verbal cognitive tests. After adjustment for age, sex, vascular risk score, years of education and depressive symptoms, ECAD remained associated with poor performance in the three cognitive domains and elevated MCA-PI with worse performance in visuospatial skills and speed. Carotid plaques and increased intracranial vascular resistance are independently associated with low cognitive functioning in Caucasian stroke and dementia-free subjects. We failed to find an independent association of intracranial large vessel stenosis with cognitive performance. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Incorporating simulation in vascular surgery education.

PubMed

Bismuth, Jean; Donovan, Michael A; O'Malley, Marcia K; El Sayed, Hosam F; Naoum, Joseph J; Peden, Eric K; Davies, Mark G; Lumsden, Alan B

2010-10-01

The traditional apprenticeship model introduced by Halsted of "learning by doing" may just not be valid in the modern practice of vascular surgery. The model is often criticized for being somewhat unstructured because a resident's experience is based on what comes through the "door." In an attempt to promote uniformity of training, multiple national organizations are currently delineating standard curricula for each trainee to govern the knowledge and cases required in a vascular residency. However, the outcomes are anything but uniform. This means that we graduate vascular specialists with a surprisingly wide spectrum of abilities. Use of simulation may benefit trainees in attaining a level of technical expertise that will benefit themselves and their patients. Furthermore, there is likely a need to establish a simulation-based certification process for graduating trainees to further ascertain minimum technical abilities. Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Transforming growth factor β family members in regulation of vascular function: in the light of vascular conditional knockouts.

PubMed

Jakobsson, Lars; van Meeteren, Laurens A

2013-05-15

Blood vessels are composed of endothelial cells, mural cells (smooth muscle cells and pericytes) and their shared basement membrane. During embryonic development a multitude of signaling components orchestrate the formation of new vessels. The process is highly dependent on correct dosage, spacing and timing of these signaling molecules. As vessels mature some cascades remain active, albeit at very low levels, and may be reactivated upon demand. Members of the Transforming growth factor β (TGF-β) protein family are strongly engaged in developmental angiogenesis but are also regulators of vascular integrity in the adult. In humans various genetic alterations within this protein family cause vascular disorders, involving disintegration of vascular integrity. Here we summarize and discuss recent data gathered from conditional and endothelial cell specific genetic loss-of-function of members of the TGF-β family in the mouse. Copyright © 2013 Elsevier Inc. All rights reserved.

High-resolution vascular tissue characterization in mice using 55MHz ultrasound hybrid imaging.

PubMed

Mahmoud, Ahmed M; Sandoval, Cesar; Teng, Bunyen; Schnermann, Jurgen B; Martin, Karen H; Mustafa, S Jamal; Mukdadi, Osama M

2013-03-01

Ultrasound and Duplex ultrasonography in particular are routinely used to diagnose cardiovascular disease (CVD), which is the leading cause of morbidity and mortality worldwide. However, these techniques may not be able to characterize vascular tissue compositional changes due to CVD. This work describes an ultrasound-based hybrid imaging technique that can be used for vascular tissue characterization and the diagnosis of atherosclerosis. Ultrasound radiofrequency (RF) data were acquired and processed in time, frequency, and wavelet domains to extract six parameters including time integrated backscatter (T(IB)), time variance (T(var)), time entropy (T(E)), frequency integrated backscatter (F(IB)), wavelet root mean square value (W(rms)), and wavelet integrated backscatter (W(IB)). Each parameter was used to reconstruct an image co-registered to morphological B-scan. The combined set of hybrid images were used to characterize vascular tissue in vitro and in vivo using three mouse models including control (C57BL/6), and atherosclerotic apolipoprotein E-knockout (APOE-KO) and APOE/A(1) adenosine receptor double knockout (DKO) mice. The technique was tested using high-frequency ultrasound including single-element (center frequency=55 MHz) and commercial array (center frequency=40 MHz) systems providing superior spatial resolutions of 24 μm and 40 μm, respectively. Atherosclerotic vascular lesions in the APOE-KO mouse exhibited the highest values (contrast) of -10.11±1.92 dB, -12.13±2.13 dB, -7.54±1.45 dB, -5.10±1.06 dB, -5.25±0.94 dB, and -10.23±2.12 dB in T(IB), T(var), T(E), F(IB), W(rms), W(IB) hybrid images (n=10, p<0.05), respectively. Control segments of normal vascular tissue showed the lowest values of -20.20±2.71 dB, -22.54±4.54 dB, -14.94±2.05 dB, -9.64±1.34 dB, -10.20±1.27 dB, and -19.36±3.24 dB in same hybrid images (n=6, p<0.05). Results from both histology and optical images showed good agreement with ultrasound findings within a maximum error of 3.6% in lesion estimation. This study demonstrated the feasibility of a high-resolution hybrid imaging technique to diagnose atherosclerosis and characterize plaque components in mouse. In the future, it can be easily implemented on commercial ultrasound systems and eventually translated into clinics as a screening tool for atherosclerosis and the assessment of vulnerable plaques. Copyright © 2012 Elsevier B.V. All rights reserved.

Application of Targeted Functional Assays to Assess a Putative Vascular Disruption Developmental Toxicity Pathway Informed By ToxCast High-Throughput Screening Data

EPA Science Inventory

Chemical perturbation of vascular development is a putative toxicity pathway which may result in developmental toxicity. EPA’s high-throughput screening (HTS) ToxCast program contains assays which measure cellular signals and biological processes critical for blood vessel develop...

[Binding studies with Ulex europaeus agglutinin I (UEA-I) of the vascular endothelium of the synovial membrane].

PubMed

Zschäbitz, A; Stofft, E

1988-01-01

The lectin binding sites of the synovium of patients with rheumatoid arthritis and osteoarthritis were investigated. It was shown that Ulex europaeus agglutinin is a constant marker of the vascular endothelium and is not induced during the course of inflammatory process in rheumatoid arthritis.

Non-invasive monitoring of vascularization of grafted engineered human oral mucosa

NASA Astrophysics Data System (ADS)

Wolf, D. E.; Seetamraju, M.; Gurjar, R. S.; Kuo, R. S.; Fasi, A.; Feinberg, S. E.

2012-03-01

Accident victims and victims of explosive devices often suffer from complex maxillofacial injuries. The lips are one of the most difficult areas of the face to reconstruct after an avulsion. Lip avulsion results in compromised facial esthetics and functions of speech and mastication. The process of reconstruction requires assessment of the vascularization of grafted ex vivo engineered tissue while it is buried underneath the skin. We describe the design and animal testing of a hand-held surgical probe based upon diffuse correlation spectroscopy to assess vascularization.

BPC 157 and blood vessels.

PubMed

Seiwerth, Sven; Brcic, Luka; Vuletic, Lovorka Batelja; Kolenc, Danijela; Aralica, Gorana; Misic, Marija; Zenko, Anita; Drmic, Domagoj; Rucman, Rudolf; Sikiric, Predrag

2014-01-01

This review focuses on the described effects of BPC 157 on blood vessels after different types of damage, and elucidate by investigating different aspects of vascular response to injury (endothelium damage, clotting, thrombosis, vasoconstriction, vasodilatation, vasculoneogenesis and edema formation) especially in connection to the healing processes. In this respect, BPC 157 was concluded to be the most potent angiomodulatory agent, acting through different vasoactive pathways and systems (e.g. NO, VEGF, FAK) and leading to optimization of the vascular response followed, as it has to be expected, by optimization of the healing process. Formation of new blood vessels involves two main, partly overlapping mechanisms, angiogenesis and vasculogenesis. The additional mechanism of arteriogenesis is involved in the formation of collaterals. In conjunction with blood vessel function, we at least have to consider leakage of fluid/proteins/plasma, resulting in edema/exudate formation as well as thrombogenesis. Blood vessels are also strongly involved in tumor biology. In this aspect, we have neoangiogenesis resulting in pathological vascularization, vascular invasion resulting in release of metastatic cells and the phenomenon of homing resulting in formation of secondary tumors--metastases.

Vascular Ageing and Exercise: Focus on Cellular Reparative Processes.

PubMed

Ross, Mark D; Malone, Eva; Florida-James, Geraint

2016-01-01

Ageing is associated with an increased risk of developing noncommunicable diseases (NCDs), such as diabetes and cardiovascular disease (CVD). The increased risk can be attributable to increased prolonged exposure to oxidative stress. Often, CVD is preceded by endothelial dysfunction, which carries with it a proatherothrombotic phenotype. Endothelial senescence and reduced production and release of nitric oxide (NO) are associated with "vascular ageing" and are often accompanied by a reduced ability for the body to repair vascular damage, termed "reendothelialization." Exercise has been repeatedly shown to confer protection against CVD and diabetes risk and incidence. Regular exercise promotes endothelial function and can prevent endothelial senescence, often through a reduction in oxidative stress. Recently, endothelial precursors, endothelial progenitor cells (EPC), have been shown to repair damaged endothelium, and reduced circulating number and/or function of these cells is associated with ageing. Exercise can modulate both number and function of these cells to promote endothelial homeostasis. In this review we look at the effects of advancing age on the endothelium and these endothelial precursors and how exercise appears to offset this "vascular ageing" process.

Arteriovenous Malformations

MedlinePlus

Arteriovenous malformations (AVMs) are defects in your vascular system. The vascular system includes arteries, veins, and capillaries. Arteries carry blood away from the heart to other organs; veins carry blood back to the heart. Capillaries connect the arteries and veins. An ...

Vascular Consequences of Aldosterone Excess and Mineralocorticoid Receptor Antagonism.

PubMed

Chrissobolis, Sophocles

2017-01-01

Aldosterone binds to mineralocorticoid receptors (MRs) on renal epithelial cells to regulate sodium and water reabsorption, and therefore blood pressure. Recently, the actions of aldosterone outside the kidney have been extensively investigated, with numerous reports of aldosterone having detrimental actions, including in the vasculature. Notably, elevated aldosterone levels are an independent cardiovascular risk factor, and in addition to causing an increase in blood pressure, aldosterone can have blood pressure-dependent and -independent effects commonly manifested in the vasculature in cardiovascular diseases, including oxidative stress, endothelial dysfunction, inflammation, remodeling, stiffening, and plaque formation. Receptor-dependent mechanisms mediating these actions include the MR expressed on vascular endothelial and smooth muscle cells, but also include the angiotensin II type 1 receptor, epidermal growth factor receptor and vascular endothelial growth factor receptor 1, with downstream mechanisms including NADPH oxidase, cyclooxygenase, glucose-6-phosphate dehydrogenase, poly-(ADP ribose) polymerase and placental growth factor. The beneficial actions of MR antagonism in experimental hypertension include improved endothelial function, reduced hypertrophy and remodeling, and in atherosclerosis beneficial actions include reduced plaque area, inflammation, oxidative stress and endothelial dysfunction. Aldosterone excess is detrimental and MR antagonism is beneficial in humans also. The emerging concept of the contribution of aldosterone/MR-induced immunity to vascular pathology will also be discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Indian-Ink Perfusion Based Method for Reconstructing Continuous Vascular Networks in Whole Mouse Brain

PubMed Central

Xue, Songchao; Gong, Hui; Jiang, Tao; Luo, Weihua; Meng, Yuanzheng; Liu, Qian; Chen, Shangbin; Li, Anan

2014-01-01

The topology of the cerebral vasculature, which is the energy transport corridor of the brain, can be used to study cerebral circulatory pathways. Limited by the restrictions of the vascular markers and imaging methods, studies on cerebral vascular structure now mainly focus on either observation of the macro vessels in a whole brain or imaging of the micro vessels in a small region. Simultaneous vascular studies of arteries, veins and capillaries have not been achieved in the whole brain of mammals. Here, we have combined the improved gelatin-Indian ink vessel perfusion process with Micro-Optical Sectioning Tomography for imaging the vessel network of an entire mouse brain. With 17 days of work, an integral dataset for the entire cerebral vessels was acquired. The voxel resolution is 0.35×0.4×2.0 µm3 for the whole brain. Besides the observations of fine and complex vascular networks in the reconstructed slices and entire brain views, a representative continuous vascular tracking has been demonstrated in the deep thalamus. This study provided an effective method for studying the entire macro and micro vascular networks of mouse brain simultaneously. PMID:24498247

Graph analysis of cell clusters forming vascular networks

NASA Astrophysics Data System (ADS)

Alves, A. P.; Mesquita, O. N.; Gómez-Gardeñes, J.; Agero, U.

2018-03-01

This manuscript describes the experimental observation of vasculogenesis in chick embryos by means of network analysis. The formation of the vascular network was observed in the area opaca of embryos from 40 to 55 h of development. In the area opaca endothelial cell clusters self-organize as a primitive and approximately regular network of capillaries. The process was observed by bright-field microscopy in control embryos and in embryos treated with Bevacizumab (Avastin), an antibody that inhibits the signalling of the vascular endothelial growth factor (VEGF). The sequence of images of the vascular growth were thresholded, and used to quantify the forming network in control and Avastin-treated embryos. This characterization is made by measuring vessels density, number of cell clusters and the largest cluster density. From the original images, the topology of the vascular network was extracted and characterized by means of the usual network metrics such as: the degree distribution, average clustering coefficient, average short path length and assortativity, among others. This analysis allows to monitor how the largest connected cluster of the vascular network evolves in time and provides with quantitative evidence of the disruptive effects that Avastin has on the tree structure of vascular networks.

Harmful Effects of the Azathioprine Metabolite 6-Mercaptopurine in Vascular Cells: Induction of Mineralization

PubMed Central

Tölle, Markus; Prüfer, Nicole; Höhne, Matthias; Zidek, Walter; van der Giet, Markus

2014-01-01

Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteo-chondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis. PMID:25029363

Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization.

PubMed

Prüfer, Jasmin; Schuchardt, Mirjam; Tölle, Markus; Prüfer, Nicole; Höhne, Matthias; Zidek, Walter; van der Giet, Markus

2014-01-01

Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteo-chondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis.

New options for vascularized bone reconstruction in the upper extremity.

PubMed

Houdek, Matthew T; Wagner, Eric R; Wyles, Cody C; Nanos, George P; Moran, Steven L

2015-02-01

Originally described in the 1970s, vascularized bone grafting has become a critical component in the treatment of bony defects and non-unions. Although well established in the lower extremity, recent years have seen many novel techniques described to treat a variety of challenging upper extremity pathologies. Here the authors review the use of different techniques of vascularized bone grafts for the upper extremity bone pathologies. The vascularized fibula remains the gold standard for the treatment of large bone defects of the humerus and forearm, while also playing a role in carpal reconstruction; however, two other important options for larger defects include the vascularized scapula graft and the Capanna technique. Smaller upper extremity bone defects and non-unions can be treated with the medial femoral condyle (MFC) free flap or a vascularized rib transfer. In carpal non-unions, both pedicled distal radius flaps and free MFC flaps are viable options. Finally, in skeletally immature patients, vascularized fibular head epiphyseal transfer can provide growth potential in addition to skeletal reconstruction.

Vascular effects of aldosterone: sorting out the receptors and the ligands.

PubMed

Feldman, Ross D; Gros, Robert

2013-12-01

Aldosterone has actions far beyond its role as a renal regulator of sodium reabsorption, and broader mechanisms of action than simply a transcriptional regulator. Aldosterone has a number of vascular effects, including regulation of vascular reactivity and vascular growth and/or development. Aldosterone-mediated effects on vascular reactivity reflect a balance between its endothelial-dependent vasodilator effects and its direct smooth muscle vasoconstrictor effects. The endothelial vasodilator effects of aldosterone are mediated by phosphatidylinositol 3-kinase-dependent activation of nitric oxide synthase. G-Protein oestrogen receptor (GPER) is a recently recognized G-protein coupled receptor (GPCR) that is activated by steroid hormones. It was first recognized as the GPCR mediating the rapid effects of oestrogens. Activation of GPER also mediates at least some of the vascular effects of aldosterone in smooth muscle and endothelial cells. In vascular endothelial cells, aldosterone activation of GPER mediates vasodilation. In contrast, activation of endothelial mineralocorticoid receptors has been linked to enhanced vasoconstrictor and/or impaired vasodilator responses. © 2013 Wiley Publishing Asia Pty Ltd.

Vascular Cells in Blood Vessel Wall Development and Disease.

PubMed

Mazurek, R; Dave, J M; Chandran, R R; Misra, A; Sheikh, A Q; Greif, D M

2017-01-01

The vessel wall is composed of distinct cellular layers, yet communication among individual cells within and between layers results in a dynamic and versatile structure. The morphogenesis of the normal vascular wall involves a highly regulated process of cell proliferation, migration, and differentiation. The use of modern developmental biological and genetic approaches has markedly enriched our understanding of the molecular and cellular mechanisms underlying these developmental events. Additionally, the application of similar approaches to study diverse vascular diseases has resulted in paradigm-shifting insights into pathogenesis. Further investigations into the biology of vascular cells in development and disease promise to have major ramifications on therapeutic strategies to combat pathologies of the vasculature. © 2017 Elsevier Inc. All rights reserved.

Frailty assessment in vascular surgery and its utility in preoperative decision making.

PubMed

Kraiss, Larry W; Beckstrom, Julie L; Brooke, Benjamin S

2015-06-01

The average patient requiring vascular surgery has become older, as life expectancy within the US population has increased. Many older patients have some degree of frailty and reside near the limit of their physiological reserve with restricted ability to respond to stressors such as surgery. Frailty assessment is an important part of the preoperative decision-making process, in order to determine whether patients are fit enough to survive the vascular surgery procedure and live long enough to benefit from the intervention. In this review, we will discuss different measures of frailty assessment and how they can be used by vascular surgery providers to improve preoperative decision making and the quality of patient care. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinicopathological correlation of psychosis and brain vascular changes in Alzheimer’s disease

PubMed Central

Ting, Simon Kang Seng; Hao, Ying; Chia, Pei Shi; Tan, Eng-King; Hameed, Shahul

2016-01-01

Psychosis is common in Alzheimer’s disease (AD). However, studies on neuropathology in vascular etiology contributing to psychosis in AD is lacking to date. The aim of this study was to investigate neuropathological vascular related changes in Alzheimer’s disease with psychosis. Data of patients with AD from the National Alzheimer’s Coordinating Center between 2005 to September 2013 was accessed and reviewed. Presence of psychosis was determined based on Neuropsychiatric Inventory Questionnaire taken from the last visit within one year prior to death, and patients were divided into psychosis positive and negative group. Comparison of clinical details and neuropathological vascular changes between the groups was performed using Wilcoxon rank sum test and Chi-square/ Fisher’s exact test. Significant variables were further included in a multivariate logistic model. Overall, 145 patients was included. Of these, 50 patients were psychosis positive. Presence of one or more cortical microinfarcts and moderate to severe arteriosclerosis was found to be positively associated with psychosis. Our results suggest vascular changes correlate with psychosis in Alzheimer’s disease. PMID:26868671

Birt-Hogg-Dubé syndrome and intracranial vascular pathologies.

PubMed

Kapoor, Rahul; Evins, Alexander I; Steitieh, Diala; Bernardo, Antonio; Stieg, Philip E

2015-12-01

Birt-Hogg-Dubé syndrome, first described in 1977, is a rare autosomal dominant condition that commonly presents with skin lesions, including fibrofolliculomas and trichodiscomas; pulmonary cysts; spontaneous pneumothoraces; and renal cancer. We present the only known cases of intracranial vascular pathologies in patients with Birt-Hogg-Dubé syndrome. We present three cases (three female; age range 18-50) of intracranial vascular lesions in Birt-Hogg-Dubé patients, including two aneurysms and one arteriovenous malformation, and review one previously reported case of carotid aplasia. Due to the rarity of Birt-Hogg-Dubé syndrome and significant variations in its clinical presentation, it is difficult to assess whether or not Birt-Hogg-Dubé patients are predisposed to intracranial vascular pathologies. We hypothesize that increased transcription of hypoxia-inducible factor 1-alpha, resulting from a mutated form of the protein folliculin transcribed by the Birt-Hogg-Dubé gene, may be associated with vascular pathogenesis in Birt-Hogg-Dubé patients and thus provide a possible molecular basis for a link between these two conditions.

White matter hyperintensities and vascular risk factors in monozygotic twins.

PubMed

Ten Kate, Mara; Sudre, Carole H; den Braber, Anouk; Konijnenberg, Elles; Nivard, Michel G; Cardoso, M Jorge; Scheltens, Philip; Ourselin, Sébastien; Boomsma, Dorret I; Barkhof, Frederik; Visser, Pieter Jelle

2018-06-01

Cerebral white matter hyperintensities (WMHs) have been associated with vascular risk factors, both of which are under genetic influence. We examined in a monozygotic twin sample whether the association between vascular risk and WMHs is influenced by overlapping genetic factors. We included 195 cognitively normal monozygotic twins (age = 70 ± 7 years), including 94 complete pairs. Regional WMH load was estimated using an automated algorithm. Vascular risk was summarized with the Framingham score. The within-twin pair correlation for total WMHs was 0.76 and for Framingham score was 0.77. Within participants, Framingham score was associated with total and periventricular WMHs (r = 0.32). Framingham score in 1 twin was also associated with total WMHs in the co-twin (r = 0.26). Up to 83% of the relation between both traits could be explained by shared genetic effects. In conclusion, monozygotic twins have highly similar vascular risk and WMH burden, confirming a genetic background for these traits. The association between both traits is largely driven by overlapping genetic factors. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

PubMed

Yahagi, Kazuyuki; Kolodgie, Frank D; Lutter, Christoph; Mori, Hiroyoshi; Romero, Maria E; Finn, Aloke V; Virmani, Renu

2017-02-01

The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification. © 2016 American Heart Association, Inc.

Robotic vascular resections during Whipple procedure.

PubMed

Allan, Bassan J; Novak, Stephanie M; Hogg, Melissa E; Zeh, Herbert J

2018-01-01

Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vascular resections. This report outlines our technique.

Effect of microgravity on renal and femoral flows during LBNP & intravenous saline load

NASA Technical Reports Server (NTRS)

Arbeille, P.; Gaffney, F. A.; Beck, L.; Coulon, J.; Porcher, M.; Blomqvist, C. G.

1996-01-01

Renal and femoral hemodynamics were studied in crew members at rest and during lower body negative pressure before and after the D-2 Spacelab mission and with intravenous saline loading. Specific measurements included renal vascular resistance, femoral arterial flow, and vascular resistance, along with other cardiovascular parameters. Cardiovascular adaptation to microgravity is discussed with a focus on changes observed in femoral and renal vascular resistance.

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.

Molecular controls of arterial morphogenesis.

PubMed

Simons, Michael; Eichmann, Anne

2015-05-08

Formation of arterial vasculature, here termed arteriogenesis, is a central process in embryonic vascular development as well as in adult tissues. Although the process of capillary formation, angiogenesis, is relatively well understood, much remains to be learned about arteriogenesis. Recent discoveries point to the key role played by vascular endothelial growth factor receptor 2 in control of this process and to newly identified control circuits that dramatically influence its activity. The latter can present particularly attractive targets for a new class of therapeutic agents capable of activation of this signaling cascade in a ligand-independent manner, thereby promoting arteriogenesis in diseased tissues. © 2015 American Heart Association, Inc.

Rationale, scope, and 20-year experience of vascular surgical training with lifelike pulsatile flow models.

PubMed

Eckstein, Hans-Henning; Schmidli, Jürg; Schumacher, Hardy; Gürke, Lorenz; Klemm, Klaus; Duschek, Nikolaus; Meile, Toni; Assadian, Afshin

2013-05-01

Vascular surgical training currently has to cope with various challenges, including restrictions on work hours, significant reduction of open surgical training cases in many countries, an increasing diversity of open and endovascular procedures, and distinct expectations by trainees. Even more important, patients and the public no longer accept a "learning by doing" training philosophy that leaves the learning curve on the patient's side. The Vascular International (VI) Foundation and School aims to overcome these obstacles by training conventional vascular and endovascular techniques before they are applied on patients. To achieve largely realistic training conditions, lifelike pulsatile models with exchangeable synthetic arterial inlays were created to practice carotid endarterectomy and patch plasty, open abdominal aortic aneurysm surgery, and peripheral bypass surgery, as well as for endovascular procedures, including endovascular aneurysm repair, thoracic endovascular aortic repair, peripheral balloon dilatation, and stenting. All models are equipped with a small pressure pump inside to create pulsatile flow conditions with variable peak pressures of ~90 mm Hg. The VI course schedule consists of a series of 2-hour modules teaching different open or endovascular procedures step-by-step in a standardized fashion. Trainees practice in pairs with continuous supervision and intensive advice provided by highly experienced vascular surgical trainers (trainer-to-trainee ratio is 1:4). Several evaluations of these courses show that tutor-assisted training on lifelike models in an educational-centered and motivated environment is associated with a significant increase of general and specific vascular surgical technical competence within a short period of time. Future studies should evaluate whether these benefits positively influence the future learning curve of vascular surgical trainees and clarify to what extent sophisticated models are useful to assess the level of technical skills of vascular surgical residents at national or international board examinations. This article gives an overview of our experiences of >20 years of practical training of beginners and advanced vascular surgeons using lifelike pulsatile vascular surgical training models. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

An integrated assessment of the vascular plant species of the Americas.

PubMed

Ulloa Ulloa, Carmen; Acevedo-Rodríguez, Pedro; Beck, Stephan; Belgrano, Manuel J; Bernal, Rodrigo; Berry, Paul E; Brako, Lois; Celis, Marcela; Davidse, Gerrit; Forzza, Rafaela C; Gradstein, S Robbert; Hokche, Omaira; León, Blanca; León-Yánez, Susana; Magill, Robert E; Neill, David A; Nee, Michael; Raven, Peter H; Stimmel, Heather; Strong, Mark T; Villaseñor, José L; Zarucchi, James L; Zuloaga, Fernando O; Jørgensen, Peter M

2017-12-22

The cataloging of the vascular plants of the Americas has a centuries-long history, but it is only in recent decades that an overview of the entire flora has become possible. We present an integrated assessment of all known native species of vascular plants in the Americas. Twelve regional and national checklists, prepared over the past 25 years and including two large ongoing flora projects, were merged into a single list. Our publicly searchable checklist includes 124,993 species, 6227 genera, and 355 families, which correspond to 33% of the 383,671 vascular plant species known worldwide. In the past 25 years, the rate at which new species descriptions are added has averaged 744 annually for the Americas, and we can expect the total to reach about 150,000. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Vascular injury is associated with increased mortality in winter sports trauma.

PubMed

Eun, John C; Bronsert, Michael; Hansen, Kristine; Moulton, Steven L; Jazaeri, Omid; Nehler, Mark; Greenberg, Joshua I

2015-01-01

Trauma is the leading cause of injury and death for individuals aged 1-44 years. Up to 8% of the US population participates in winter sports, and although vascular injuries are uncommon in these activities, little is published in this area. We sought to identify the incidence, injury patterns, and outcomes of vascular injuries resulting from winter sports trauma. Patients with winter sports trauma and the subset with vascular injuries were identified by accessing the National Trauma Data Bank querying years 2007-2010. Patients with and without vascular injuries were then compared. Admission variables included transport time, emergency department hypotension (systolic blood pressure < 90), Glasgow Coma Scale ≤ 8, Injury Severity Score ≥ 25, fractures, solid organ injury, and vascular injury. Outcomes were analyzed and associations with vascular injuries were determined. A total of 2,298 patients were identified with winter sports-related trauma and 28 (1.2%) had associated vascular injuries. Overall, the top 3 injuries were head trauma (16.7%), thoracic vertebral fractures (5.5%), and lumbar vertebral fractures (5.1%). The most common associated vascular injures were to the popliteal artery (17.7%), splenic artery (14.7%), and brachial blood vessels (14.7%). In the entire cohort, 1 patient (0.04%) suffered an amputation and 15 patients (0.7%) died. There were no amputations in the vascular injury group. Mortality was 0.6% in patients without a vascular injury compared with 7.1% of those with a vascular injury (P = 0.01). Although vascular injury is an uncommon associated finding in winter sports trauma, it is associated with a significant increase in mortality. These findings highlight the need for rapid identification of traumatic vascular injuries, which predicts worse overall outcomes in this patient population. Copyright © 2015 Elsevier Inc. All rights reserved.

Reactive oxygen species, vascular Noxs, and hypertension: focus on translational and clinical research.

PubMed

Montezano, Augusto C; Touyz, Rhian M

2014-01-01

Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redox-sensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic.

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.

Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1.

PubMed

Kozel, Beth A; Danback, Joshua R; Waxler, Jessica L; Knutsen, Russell H; de Las Fuentes, Lisa; Reusz, Gyorgy S; Kis, Eva; Bhatt, Ami B; Pober, Barbara R

2014-01-01

Williams syndrome is caused by the deletion of 26 to 28 genes, including elastin, on human chromosome 7. Elastin insufficiency leads to the cardiovascular hallmarks of this condition, namely focal stenosis and hypertension. Extrapolation from the Eln(+/-) mouse suggests that affected people may also have stiff vasculature, a risk factor for stroke, myocardial infarction, and cardiac death. NCF1, one of the variably deleted Williams genes, is a component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex and is involved in the generation of oxidative stress, making it an interesting candidate modifier for vascular stiffness. Using a case-control design, vascular stiffness was evaluated by pulse wave velocity in 77 Williams cases and matched controls. Cases had stiffer conducting vessels than controls (P<0.001), with increased stiffness observed in even the youngest children with Williams syndrome. Pulse wave velocity increased with age at comparable rates in cases and controls, and although the degree of vascular stiffness varied, it was seen in both hypertensive and normotensive Williams participants. Use of antihypertensive medication and extension of the Williams deletion to include NCF1 were associated with protection from vascular stiffness. These findings demonstrate that vascular stiffness is a primary vascular phenotype in Williams syndrome and that treatment with antihypertensives or agents inhibiting oxidative stress may be important in managing patients with this condition, potentially even those who are not overtly hypertensive.

Arterial complications of vascular Ehlers-Danlos syndrome.

PubMed

Eagleton, Matthew J

2016-12-01

Vascular Ehlers-Danlos syndrome (EDS) is a relatively rare genetic syndrome that occurs owing to disorders in the metabolism of fibrillary collagen. These defects affect the soft connective tissues resulting in abnormalities in the skin, joints, hollow organs, and blood vessels. Patients with these defects frequently present at a young age with spontaneous arterial complications involving the medium-sized arteries. Complications involving the hollow organs, such as spontaneous colonic perforation, are observed as well. Given the fragility of the soft tissue, open and endovascular intervention on patients with vascular EDS is fraught with high complication rates. A PubMed search was performed to identify manuscripts published related to vascular EDS. This search included more than 747 articles. These findings were cross-referenced using key terms, including endovascular, embolization, surgery, genetics, pathophysiology, connective tissue disorders, vascular complications, systematic review, type III collagen, and COL3A1. The references in key articles and review articles were evaluated for additional resources not identified in the PubMed search. Care must be taken to balance the risk of intervention vs the risk of continued observation. Life-threatening hemorrhage, however, mandates intervention. With careful, altered approaches to tissue handling, endovascular approaches may provide a safer option for managing the arterial complications observed in patients with vascular EDS. Additional hope may also be found in the use of pharmacologic agents that reduce the incidence and severity of the arterial complications. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Analysis of homeobox gene action may reveal novel angiogenic pathways in normal placental vasculature and in clinical pregnancy disorders associated with abnormal placental angiogenesis.

PubMed Central

Murthi, Padma; Abumaree, Mohamed; Kalionis, Bill

2014-01-01

Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. Homeobox genes comprise an important family of transcription factors, which are characterized by a well conserved DNA binding motif; the homeodomain. The specificity of the homeodomain allows the transcription factor to bind to the promoter regions of batteries of target genes and thereby regulates their expression. Target genes identified for homeodomain proteins have been shown to control fundamental cell processes such as proliferation, differentiation, and apoptosis. We and others have reported that homeobox genes are expressed in the placental vasculature, but our knowledge of their downstream target genes is limited. This review highlights the importance of studying the cellular and molecular mechanisms by which homeobox genes and their downstream targets may regulate important vascular cellular processes such as proliferation, migration, and endothelial tube formation, which are essential for placental vasculogenesis and angiogenesis. A better understanding of the molecular targets of homeobox genes may lead to new therapies for aberrant angiogenesis associated with clinically important pregnancy pathologies, including fetal growth restriction and preeclampsia. PMID:24926269

Biomaterials-based 3D cell printing for next-generation therapeutics and diagnostics.

PubMed

Jang, Jinah; Park, Ju Young; Gao, Ge; Cho, Dong-Woo

2018-02-01

Building human tissues via 3D cell printing technology has received particular attention due to its process flexibility and versatility. This technology enables the recapitulation of unique features of human tissues and the all-in-one manufacturing process through the design of smart and advanced biomaterials and proper polymerization techniques. For the optimal engineering of tissues, a higher-order assembly of physiological components, including cells, biomaterials, and biomolecules, should meet the critical requirements for tissue morphogenesis and vascularization. The convergence of 3D cell printing with a microfluidic approach has led to a significant leap in the vascularization of engineering tissues. In addition, recent cutting-edge technology in stem cells and genetic engineering can potentially be adapted to the 3D tissue fabrication technique, and it has great potential to shift the paradigm of disease modeling and the study of unknown disease mechanisms required for precision medicine. This review gives an overview of recent developments in 3D cell printing and bioinks and provides technical requirements for engineering human tissues. Finally, we propose suggestions on the development of next-generation therapeutics and diagnostics. 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.

Strength and Persistence of Energy-Based Vessel Seals Rely on Tissue Water and Glycosaminoglycan Content.

PubMed

Kramer, Eric A; Cezo, James D; Fankell, Douglas P; Taylor, Kenneth D; Rentschler, Mark E; Ferguson, Virginia L

2016-11-01

Vessel ligation using energy-based surgical devices is steadily replacing conventional closure methods during minimally invasive and open procedures. In exploring the molecular nature of thermally-induced tissue bonds, novel applications for surgical resection and repair may be revealed. This work presents an analysis of the influence of unbound water and hydrophilic glycosaminoglycans on the formation and resilience of vascular seals via: (a) changes in pre-fusion tissue hydration, (b) the enzymatic digestion of glycosaminoglycans (GAGs) prior to fusion and (c) the rehydration of vascular seals following fusion. An 11% increase in pre-fusion unbound water led to an 84% rise in vascular seal strength. The digestion of GAGs prior to fusion led to increases of up to 82% in seal strength, while the rehydration of native and GAG-digested vascular seals decreased strengths by 41 and 44%, respectively. The effects of increased unbound water content prior to fusion combined with the effects of seal rehydration after fusion suggest that the heat-induced displacement of tissue water is a major contributor to tissue adhesion during energy-based vessel sealing. The effects of pre-fusion GAG-digestion on seal integrity indicate that GAGs are inhibitory to the bond formation process during thermal ligation. GAG digestion may allow for increased water transport and protein interaction during the fusion process, leading to the formation of stronger bonds. These findings provide insight into the physiochemical nature of the fusion bond, its potential for optimization in vascular closure and its application to novel strategies for vascular resection and repair.

Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

PubMed

Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

2015-05-01

During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue ingrowth and remodeling processes of the bone substitute. Extrinsic vessels contribute to faster vascularization and finally anastomose with intrinsic vasculature, allowing microvascular transplantation of the bone substitute after a shorter prevascularization time than using the intrinsic method only. It can be reasonably assumed that the usage of perforated chambers can significantly reduce the time until transplantation of bone constructs. Finally, this study paves the way for further preclinical testing for proof of the concept as a basis for early clinical applicability.

Immunohistochemical and histomorphometric evaluation of vascular distribution in intact canine cranial cruciate ligament.

PubMed

Hayashi, Kei; Bhandal, Jitender; Kim, Sun Young; Rodriguez, Carlos O; Entwistle, Rachel; Naydan, Diane; Kapatkin, Amy; Stover, Susan M

2011-02-01

To (1) describe vascular distribution in the grossly intact canine cranial cruciate ligament (CCL) using immunohistochemical techniques specific to 2 components of blood vessels (factor VIII for endothelial cells, laminin for basement membrane); and (2) compare the vascularity in different areas of interest (craniomedial versus caudolateral bands; core versus epiligamentous regions; and proximal versus middle versus distal portions) in the intact normal canine CCL. In vitro study. Large, mature dogs (n=7) of breeds prone to CCL disease that were euthanatized for nonorthopedic conditions. Intact CCL were collected from fresh canine cadavers free from stifle pathology. CCL tissue was processed for immunohistochemistry and stained for factor VIII and laminin. Vascular density was determined by histomorphometric analysis. Specific vascular staining was sparsely identified throughout the CCL; however, the proximal portion of the CCL appears to have a greater number of vessels than the middle or distal portion of the ligament. The CCL is a hypovascular tissue and its vascular distribution is not homogeneous. © Copyright 2010 by The American College of Veterinary Surgeons.

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.

In Vivo Analysis of the Neurovascular Niche in the Developing Xenopus Brain

PubMed Central

Li, Jianli

2017-01-01

Abstract The neurovascular niche is a specialized microenvironment formed by the interactions between neural progenitor cells (NPCs) and the vasculature. While it is thought to regulate adult neurogenesis by signaling through vascular-derived soluble cues or contacted-mediated cues, less is known about the neurovascular niche during development. In Xenopus laevis tadpole brain, NPCs line the ventricle and extend radial processes tipped with endfeet to the vascularized pial surface. Using in vivo labeling and time-lapse imaging in tadpoles, we find that intracardial injection of fluorescent tracers rapidly labels Sox2/3-expressing NPCs and that vascular-circulating molecules are endocytosed by NPC endfeet. Confocal imaging indicates that about half of the endfeet appear to appose the vasculature, and time-lapse analysis of NPC proliferation and endfeet-vascular interactions suggest that proliferative activity does not correlate with stable vascular apposition. Together, these findings characterize the neurovascular niche in the developing brain and suggest that, while signaling to NPCs may occur through vascular-derived soluble cues, stable contact between NPC endfeet and the vasculature is not required for developmental neurogenesis. PMID:28795134

Temperature-dependent rate models of vascular cambium cell mortality

Treesearch

Matthew B. Dickinson; Edward A. Johnson

2004-01-01

We use two rate-process models to describe cell mortality at elevated temperatures as a means of understanding vascular cambium cell death during surface fires. In the models, cell death is caused by irreversible damage to cellular molecules that occurs at rates that increase exponentially with temperature. The models differ in whether cells show cumulative effects of...

Benign vascular proliferation in a lymph node following acute toxoplasmosis. A differential diagnosis from Kaposi's sarcoma.

PubMed

Rousselet, M C; Saint-André, J P; Beaufils, J M; Diebold, J

1988-12-01

We describe an unusual intranodal vascular proliferation following acute toxoplasmosis in a man. This proliferation is distinct from other benign vasoformative nodal lesions. It could be interpreted as a reactive healing process that might be misdiagnosed as nodal Kaposi's sarcoma. Some criteria to avoid such misdiagnosis are presented.

Spectroscopic Biomarkers for Monitoring Wound Healing and Infection in Wounds

DTIC Science & Technology

2014-06-01

injuries, burns, acute vascular disruption, blastwave-associated pressure injuries, air, thrombotic, and fat embolism , and compartment syndrome. In...damage and compromised local circulation often associated with overt vascular injury. These injuries include traumatic amputations, open fractures , crush

Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

PubMed

Lorius, Natacha; Locascio, Joseph J; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Viswanathan, Anand; Marshall, Gad A

2015-01-01

We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E ε4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E ε4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.

High-flow vascular malformation treatment using ultrasound-guided laser combined with polidocanol sclerotherapy.

PubMed

Zhang, Yan; Zhou, Ping; Li, Lan; Li, Jia-le

2015-07-01

The current treatment for vascular malformations includes surgery, sclerotherapy, and embolization. However, each method has its limitations, such as recurrence, complications, scarring, and radiation exposure. Therefore, identifying an effective, minimally invasive treatment that reduces lesion recurrence is particularly important. We describe in detail a patient who received treatment with ultrasound-guided laser interruption of feeding vessels combined with polidocanol sclerotherapy after the recurrence of forearm high-flow vascular malformation.

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.

How platelets safeguard vascular integrity

PubMed Central

Ho-Tin-Noé, Benoit; Demers, Mélanie; Wagner, Denisa D

2011-01-01

Summary The haemostatic role of platelets was established in the 1880s by Bizzozero who observed their ability to adhere and aggregate at sites of vascular injury. It was only some 80 years later that the function of platelets in maintaining the structural integrity of intact blood vessels was reported by Danielli. Danielli noted that platelets help preserve the barrier function of endothelium during organ perfusion. Subsequent studies have demonstrated further that platelets are continuously needed to support intact mature blood vessels. More recently, platelets were shown to safeguard developing vessels, lymphatics, as well as the microvasculature at sites of leukocyte infiltration, including inflamed organs and tumours. Interestingly, from a mechanistic point of view, the supporting role of platelets in these various vessels does not necessarily involve the well-understood process of platelet plug formation but, rather, may rely on secretion of the various platelet granules and their many active components. The present review focuses on these nonconventional aspects of platelet biology and function by presenting situations in which platelets intervene to maintain vascular integrity and discusses possible mechanisms of their actions. We propose that modulating these newly described platelet functions may help treat haemorrhage as well as treat cancer by increasing the efficacy of drug delivery to tumours. PMID:21781242

Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing

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

Dumortier, Jerome; Streblow, Daniel N.; Moses, Ashlee V.

2008-07-01

Human cytomegalovirus (HCMV) is implicated in the acceleration of a number of vascular diseases including transplant vascular sclerosis (TVS), the lesion associated with chronic rejection (CR) of solid organ transplants. Although the virus persists in the allograft throughout the course of disease, few cells are directly infected by CMV. This observation is in contrast to the global effects that CMV has on the acceleration of TVS/CR, suggesting that CMV infection indirectly promotes the vascular disease process. Recent transcriptome analysis of CMV-infected heart allografts indicates that the virus induces cytokines and growth factors associated with angiogenesis (AG) and wound healing (WH),more » suggesting that CMV may accelerate TVS/CR through the induction and secretion of AG/WH factors from infected cells. We analyzed virus-free supernatants from HCMV-infected cells (HCMV secretomes) for growth factors, by mass spectrometry and immunoassays, and found that the HCMV secretome contains over 1,000 cellular proteins, many of which are involved in AG/WH. Importantly, functional assays demonstrated that CMV but not herpes simplex virus secretomes not only induce AG/WH but also promote neovessel stabilization and endothelial cell survival for 2 weeks. These findings suggest that CMV acceleration of TVS occurs through virus-induced growth factors and cytokines in the CMV secretome.« less

The pivotal role of angiogenesis in a multi-scale modeling of tumor growth exhibiting the avascular and vascular phases.

PubMed

Salavati, Hooman; Soltani, M; Amanpour, Saeid

2018-05-06

The mechanisms involved in tumor growth mainly occur at the microenvironment, where the interactions between the intracellular, intercellular and extracellular scales mediate the dynamics of tumor. In this work, we present a multi-scale model of solid tumor dynamics to simulate the avascular and vascular growth as well as tumor-induced angiogenesis. The extracellular and intercellular scales are modeled using partial differential equations and cellular Potts model, respectively. Also, few biochemical and biophysical rules control the dynamics of intracellular level. On the other hand, the growth of melanoma tumors is modeled in an animal in-vivo study to evaluate the simulation. The simulation shows that the model successfully reproduces a completed image of processes involved in tumor growth such as avascular and vascular growth as well as angiogenesis. The model incorporates the phenotypes of cancerous cells including proliferating, quiescent and necrotic cells, as well as endothelial cells during angiogenesis. The results clearly demonstrate the pivotal effect of angiogenesis on the progression of cancerous cells. Also, the model exhibits important events in tumor-induced angiogenesis like anastomosis. Moreover, the computational trend of tumor growth closely follows the observations in the experimental study. Copyright © 2018 Elsevier Inc. All rights reserved.

Stem development through vascular tissues: EPFL-ERECTA family signaling that bounces in and out of phloem.

PubMed

Tameshige, Toshiaki; Ikematsu, Shuka; Torii, Keiko U; Uchida, Naoyuki

2017-01-01

Plant cells communicate with each other using a variety of signaling molecules. Recent studies have revealed that various types of secreted peptides, as well as phytohormones known since long ago, mediate cell-cell communication in diverse contexts of plant life. These peptides affect cellular activities, such as proliferation and cell fate decisions, through their perception by cell surface receptors located on the plasma membrane of target cells. ERECTA (ER), an Arabidopsis thaliana receptor kinase gene, was first identified as a stem growth regulator, and since then an increasing number of studies have shown that ER is involved in a wide range of developmental and physiological processes. In particular, molecular functions of ER have been extensively studied in stomatal patterning. Furthermore, the importance of ER signaling in vascular tissues of inflorescence stems, especially in phloem cells, has recently been highlighted. In this review article, first we briefly summarize the history of ER research including studies on stomatal development, then introduce ER functions in vascular tissues, and discuss its interactions with phytohormones and other receptor kinase signaling pathways. Future questions and challenges will also be addressed. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Pictorial essay: Vascular interventions in extra cranial head and neck

PubMed Central

Kulkarni, Suyash S; Shetty, Nitin S; Dharia, Tejas P; Polnaya, Ashwin M

2012-01-01

Medicine is an ever changing field and interventional radiology (IR) procedures are becoming increasingly popular because of high efficacy and its minimally invasive nature of the procedure. Management of disease processes in the extra cranial head and neck (ECHN) has always been a challenge due to the complex anatomy of the region. Cross sectional imaging of the ECHN has grown and evolved tremendously and occupies a pivotal and integral position in the clinical management of variety of head and neck pathologies. Advances in angiographic technologies including flat panel detector systems, biplane, and 3-dimensional rotational angiography have consolidated and expanded the role of IR in the management of various ECHN pathologies. The ECHN is at cross roads between the origins of great vessels and the cerebral vasculature. Thorough knowledge of functional and technical aspects of neuroangiography is essential before embarking on head and neck vascular interventions. The vessels of the head and neck can be involved by infectious and inflammatory conditions, get irradiated during radiotherapy and injured due to trauma or iatrogenic cause. The ECHN is also a common site for various hypervascular neoplasms and vascular malformations, which can be treated with endovascular and percutaneous embolization. This pictorial essay provides a review of variety of ECHN pathologies which were managed by various IR procedures using different approaches. PMID:23833428

Normalized pulse volume (NPV) derived photo-plethysmographically as a more valid measure of the finger vascular tone.

PubMed

Sawada, Y; Tanaka, G; Yamakoshi, K

2001-05-01

Normalized pulse volume (NPV) was advocated as a more valid measure for the assessment of finger vascular tone. Based on the optical model in the finger tip expressed by Lambert--Beer's law, NPV is expressed as Delta I(a)/I. Here, Delta I(a) is the intensity of pulsatile component superimposed on the transmitted light (I). Theoretically, NPV seems to be superior to the conventional pulse volume (PV; corresponding to Delta I(a)). Firstly, NPV is in direct proportion to Delta V(a), which is the pulsatile component of the arterial blood volume, in a more exact manner. Relatedly, NPV can be processed as if it is an absolute value. Secondly, the sensitivity of NPV during stressful stimulations is expected to be higher. These expectations were supported experimentally using 13 male students. Firstly, the correlation between cutaneous vascular resistance in the finger tip (CVR) and NPV was higher than that between CVR and PV among all the subjects, although there was not much difference between these correlations within each subject. Secondly, NPV decreased much more than PV during mental stress. Some limitations of the present study were addressed, including the point that certain factors can violate the direct proportional relationship of NPV and PV to Delta V(a).

Delayed cutaneous wound healing in aged rats compared to younger ones.

PubMed

Soybir, Onur C; Gürdal, Sibel Ö; Oran, Ebru Ş; Tülübaş, Feti; Yüksel, Meral; Akyıldız, Ayşenur İ; Bilir, Ayhan; Soybir, Gürsel R

2012-10-01

Delayed wound healing in elderly males is a complex process in which the factors responsible are not fully understood. This study investigated the hormonal, oxidative and angiogenic factors affecting wound healing in aged rats. Two groups consisting of eight healthy male Wistar Albino rats [young (30 ± 7 days) and aged (360 ± 30 days)], and a cutaneous incision wound healing model were used. Scar tissue samples from wounds on the 7th, 14th and 21st days of healing were evaluated for hydroxyproline and vascular endothelial growth factor content. Macrophage, lymphocyte, fibroblast and polymorphonuclear cell infiltration; collagen formation and vascularization were assessed by light and electron microscopy. The free oxygen radical content of the wounds was measured by a chemiluminescence method. Blood sample analysis showed that the hydroxyproline and total testosterone levels were significantly higher, and the oxygen radical content was significantly lower in young rats. Histopathological, immunohistochemical and ultrastructural evaluations revealed higher amounts of fibroblasts and collagen fibers, and more vascularization in young rats. These results are indicative of the delayed wound healing in aged rats. A combination of multiple factors including hormonal regulation, free oxygen radicals and impaired angiogenesis appears to be the cause of delayed cutaneous healing. © 2011 The Authors. International Wound Journal © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Demographic Risk Factors for Vascular Lesions as Etiology of Intraventricular Hemorrhage in Prospectively Screened Cases

PubMed Central

Fam, Maged; Pang, Alice; Zeineddine, Hussein A.; Mayo, Steven; Stadnik, Agnieszka; Jesselson, Michael; Zhang, Lingjiao; Dlugash, Rachel; Ziai, Wendy; Hanley, Daniel; Awad, Issam A.

2017-01-01

Background Spontaneous intraventricular hemorrhage (IVH) is associated with high rates of morbidity and mortality despite critical care and other advances. An important step in clinical management is to confirm/rule out an underlying vascular lesion, which influences further treatment, potential for further bleeding and prognosis. Our aim is to compare demographic and clinical characteristics between IVH patients with and without an underlying vascular lesion, and among cohorts with different vascular lesions. Methods We analyzed prospectively collected data of IVH patients screened for eligibility as part of the Clot Lysis: Evaluation Accelerated Resolution of Intraventricular Hemorrhage-CLEAR Phase III clinical trial. The trial adopted a structured screening process to systematically exclude patients with an underlying vascular lesion as etiology of IVH. We collected age, sex, ethnicity and primary diagnosis on these cases and vascular lesions were categorized prospectively as aneurysm, vascular malformation (arteriovenous malformation, dural arteriovenous fistula, cavernoma), Moyamoya disease or other vascular lesion. We excluded cases < 18 or > 80 years of age. Baseline characteristics were compared between the CLEAR group (IVH screened without vascular lesion) and the group of IVH patients screened and excluded from CLEAR because of an identified vascular lesion. We further analyzed the differential demographic and clinical characteristics among subcohorts with different vascular lesions. Results 10,538 consecutive IVH cases were prospectively screened for the trial between 2011 and 2015. 496 cases (4.7%) screened negative for underlying vascular lesion, met the inclusion criteria and were enrolled in the trial (no vascular etiology group), and 1,205 cases (11.4%) were concurrently screened and excluded from the trial because of a demonstrated underlying vascular lesion (vascular etiology group). Cases with vascular lesion were less likely to be older than 45 years of age (OR 0.28 CI 0.20–0.40), African-American (OR 0.23 CI 0.18–0.31) or male (OR 0.48 CI 0.38–0.60), and more likely to present with primary IVH (OR 1.85 CI 1.37–2.51) compared to those with no vascular etiology (p<0.001). Other demographic factors were associated with specific vascular lesion etiologies. A combination of demographic features increases the association with the absence of vascular lesion, but not with absolute reliability (OR 0.1, CI 0.06–0.17, p<0.001). Conclusion An underlying vascular lesion as etiology of intraventricular hemorrhage cannot be excluded solely by demographic parameters in any patient. Some form of vascular imaging is necessary in screening patients before contemplating interventions like intraventricular fibrinolysis, where safety may be impacted by the presence of vascular lesion. PMID:28245439

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement

PubMed Central

Sachdev, Perminder; Kalaria, Raj; O’Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V.; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Background Several sets of diagnostic criteria have been published for vascular dementia (VaD) since the 1960s. The continuing ambiguity in VaD definition warrants a critical re-examination. Methods Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the DSM-5 Task Force. Results Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent co-occurrence of Alzheimer’s disease pathology emphasized. Conclusions The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathological validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. PMID:24632990

Non-invasive dynamic near-infrared imaging and quantification of vascular leakage in vivo.

PubMed

Proulx, Steven T; Luciani, Paola; Alitalo, Annamari; Mumprecht, Viviane; Christiansen, Ailsa J; Huggenberger, Reto; Leroux, Jean-Christophe; Detmar, Michael

2013-07-01

Preclinical vascular research has been hindered by a lack of methods that can sensitively image and quantify vascular perfusion and leakage in vivo. In this study, we have developed dynamic near-infrared imaging methods to repeatedly visualize and quantify vascular leakage in mouse skin in vivo, and we have applied these methods to transgenic mice with overexpression of vascular endothelial growth factors VEGF-A or -C. Near-infrared dye conjugates were developed to identify a suitable vascular tracer that had a prolonged circulation lifetime and slow leakage into normal tissue after intravenous injection. Dynamic simultaneous imaging of ear skin and a large blood vessel in the leg enabled determination of the intravascular signal (blood volume fraction) from the tissue signal shortly after injection and quantifications of vascular leakage into the extravascular tissue over time. This method allowed for the sensitive detection of increased blood vascularity and leakage rates in K14-VEGF-A transgenic mice and also reliably measured inflammation-induced changes of vascularity and leakage over time in the same mice. Measurements after injection of recombinant VEGF-A surprisingly revealed increased blood vascular leakage and lymphatic clearance in K14-VEGF-C transgenic mice which have an expanded cutaneous lymphatic vessel network, potentially indicating unanticipated effects of lymphatic drainage on vascular leakage. Increased vascular leakage was also detected in subcutaneous tumors, confirming that the method can also be applied to deeper tissues. This new imaging method might facilitate longitudinal investigations of the in vivo effects of drug candidates, including angiogenesis inhibitors, in preclinical disease models.

Non-invasive dynamic near-infrared imaging and quantification of vascular leakage in vivo

PubMed Central

Proulx, Steven T.; Luciani, Paola; Alitalo, Annamari; Mumprecht, Viviane; Christiansen, Ailsa J.; Huggenberger, Reto

2013-01-01

Preclinical vascular research has been hindered by a lack of methods that can sensitively image and quantify vascular perfusion and leakage in vivo. In this study, we have developed dynamic near-infrared imaging methods to repeatedly visualize and quantify vascular leakage in mouse skin in vivo, and we have applied these methods to transgenic mice with overexpression of vascular endothelial growth factors VEGF-A or -C. Near-infrared dye conjugates were developed to identify a suitable vascular tracer that had a prolonged circulation lifetime and slow leakage into normal tissue after intravenous injection. Dynamic simultaneous imaging of ear skin and a large blood vessel in the leg enabled determination of the intravascular signal (blood volume fraction) from the tissue signal shortly after injection and quantifications of vascular leakage into the extravascular tissue over time. This method allowed for the sensitive detection of increased blood vascularity and leakage rates in K14-VEGF-A transgenic mice and also reliably measured inflammation-induced changes of vascularity and leakage over time in the same mice. Measurements after injection of recombinant VEGF-A surprisingly revealed increased blood vascular leakage and lymphatic clearance in K14-VEGF-C transgenic mice which have an expanded cutaneous lymphatic vessel network, potentially indicating unanticipated effects of lymphatic drainage on vascular leakage. Increased vascular leakage was also detected in subcutaneous tumors, confirming that the method can also be applied to deeper tissues. This new imaging method might facilitate longitudinal investigations of the in vivo effects of drug candidates, including angiogenesis inhibitors, in preclinical disease models. PMID:23325334

Correlation of near-infrared spectroscopy and transcranial magnetic stimulation of the motor cortex in overt reading and musical tasks.

PubMed

Lo, Y L; Zhang, H H; Wang, C C; Chin, Z Y; Fook-Chong, S; Gabriel, C; Guan, C T

2009-01-01

In overt reading and singing tasks, actual vocalization of words in a rhythmic fashion is performed. During execution of these tasks, the role of underlying vascular processes in relation to cortical excitability changes in a spatial manner is uncertain. Our objective was to investigate cortical excitability changes during reading and singing with transcranial magnetic stimulation (TMS), as well as vascular changes with nearinfrared spectroscopy (NIRS). Findings with TMS and NIRS were correlated. TMS and NIRS recordings were performed in 5 normal subjects while they performed reading and singing tasks separately. TMS was applied over the left motor cortex at 9 positions 2.5 cm apart. NIRS recordings were made over these identical positions. Although both TMS and NIRS showed significant mean cortical excitability and hemodynamic changes from baseline during vocalization tasks, there was no significant spatial correlation of these changes evaluated with the 2 techniques over the left motor cortex. Our findings suggest that increased left-sided cortical excitability from overt vocalization tasks in the corresponding "hand area" were the result of "functional connectivity," rather than an underlying "vascular overflow mechanism" from the adjacent speech processing or face/mouth areas. Our findings also imply that functional neurophysiological and vascular methods may evaluate separate underlying processes, although subjects performed identical vocalization tasks. Future research combining similar methodologies should embrace this aspect and harness their separate capabilities.

From hemobiology to vascular disease: a review of the potential of gliclazide to influence the pathogenesis of diabetic vascular disease.

PubMed

Jennings, P E

1994-01-01

Patients with type II diabetes commonly die from thrombotic vascular disease. Large vessel occlusion due to thrombosis or atherosclerotic stenosis is a process accelerated by diabetes and results in premature death. Diabetic small vessel disease, with its unique microangiopathic process, underlies many of the large vessel changes as well as causing retinopathy and nephropathy. The microangiopathic changes produce a prothrombotic tendency that has been widely reported in type II diabetes. There is reduced endothelial cell production of prostacyclin and the activators of fibrinolysis, together with increased platelet reactivity. In addition, there is increased lipid peroxidation and oxidative stress due to excess free-radical activity and impaired antioxidant defenses particularly in the presence of microvascular disease. The development of many of these abnormalities is associated with poor long-term glycemic control. However, the changes are also seen in atherosclerosis in nondiabetic patients where the progression of the disease can be modified by antiplatelet agents and antioxidants. The process of vascular damage is accelerated by diabetes, often due to co-existing disease and aging, although it is not clear that improvement in long-term glycemic control by lowering blood glucose levels to near to the nondiabetic state reduces the development of small and large vessel disease. Although the biochemical mechanism underlying this observation remains uncertain, protein glycosylation and increased platelet reactivity are implicated and interrelated. Increased oxidative stress due to excess free-radical activity may be central to diabetic vascular disease as endothelial cell damage, lipoprotein oxidation, modification of both platelet reactivity and arachidonic acid cascade are all properties of free radicals and their reaction products lipid peroxides.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Arterial Diameters as a Risk Factor for Vascular Events.

PubMed

Gutierrez, Jose; Cheung, Ken; Bagci, Ahmet; Rundek, Tatjana; Alperin, Noam; Sacco, Ralph L; Wright, Clinton B; Elkind, Mitchell S V

2015-08-06

Arterial luminal diameters are routinely used to assess for vascular disease. Although small diameters are typically considered pathological, arterial dilatation has also been associated with disease. We hypothesize that extreme arterial diameters are biomarkers of the risk of vascular events. Participants in the Northern Manhattan Study who had a time-of-flight magnetic resonance angiography were included in this analysis (N=1034). A global arterial Z-score, called the brain arterial remodeling (BAR) score, was obtained by averaging the measured diameters within each individual. Individuals with a BAR score <-2 SDs were considered to have the smallest diameters, individuals with a BAR score >-2 and <2 SDs had average diameters, and individuals with a BAR score >2 SDs had the largest diameters. All vascular events were recorded prospectively after the brain magnetic resonance imaging. Spline curves and incidence rates were used to test our hypothesis. The association of the BAR score with death (P=0.001), vascular death (P=0.02), any vascular event (P=0.05), and myocardial infarction (P=0.10) was U-shaped except for ischemic stroke (P=0.74). Consequently, incidence rates for death, vascular death, myocardial infarction, and any vascular event were higher in individuals with the largest diameters, whereas individuals with the smallest diameters had a higher incidence of death, vascular death, any vascular event, and ischemic stroke compared with individuals with average diameters. The risk of death, vascular death, and any vascular event increased at both extremes of brain arterial diameters. The pathophysiology linking brain arterial remodeling to systemic vascular events needs further research. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Risk Factors for Vascular Occlusive Events and Death Due to Bleeding in Trauma Patients; an Analysis of the CRASH-2 Cohort

PubMed Central

Pealing, Louise; Perel, Pablo; Prieto-Merino, David; Roberts, Ian

2012-01-01

Background Vascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding. Methods and Findings We conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) [1]. We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all p<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all p<0.001). Conclusions Patients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients. PMID:23251374

VEGF signaling inside vascular endothelial cells and beyond

PubMed Central

Eichmann, Anne; Simons, Michael

2014-01-01

Vascular endothelial growth factor-A (VEGF-A) has long been recognized as the key regulator of vascular development and function in health and disease. VEGF is a secreted polypeptide that binds to transmembrane tyrosine kinase VEGF receptors on the plasma membrane, inducing their dimerization, activation and assembly of a membrane-proximal signaling complex. Recent studies have revealed that many key events of VEGFR signaling occur inside the endothelial cell and are regulated by endosomal receptor trafficking. Plasma membrane VEGFR interacting molecules, including vascular guidance receptors Neuropilins and Ephrins also regulate VEGFR endocytosis and trafficking. VEGF signaling is increasingly recognized for its roles outside of the vascular system, notably during neural development, and blood vessels regulate epithelial branching morphogenesis. We review here recent advances in our understanding of VEGF signaling and its biological roles. PMID:22366328

Vascularized bone graft for scaphoid nonunions.

PubMed

Mih, Alexander D

2004-09-01

Scaphoid fracture nonunion remains a challenging problem that may persist despite traditional methods of bone grafting and internal fixation. The alteration of wrist mechanics created by nonunion as well as the development of avascular necrosis leads to degenerative change of the radiocarpal joint accompanied by loss of motion and pain. The use of a vascularized bone graft has the theoretical benefit of increased blood flow that exceeds that of nonvascularized grafts. Numerous sources of vascularized bone graft have been described, including those from remote sites as well as from the carpus and distal radius. Knowledge of the blood supply to the distal radius has allowed for development of several vascularized bone graft harvest sites. The results of vascularized bone grafting from the distal radius have been encouraging, with numerous authors reporting the successful treatment of scaphoid nonunions.

Inflammatory, metabolic, and genetic mechanisms of vascular calcification

PubMed Central

Demer, Linda L.; Tintut, Yin

2014-01-01

This review centers on updating the active research area of vascular calcification. This pathology underlies substantial cardiovascular morbidity and mortality, through adverse mechanical effects on vascular compliance, vasomotion, and, most likely, plaque stability. Biomineralization is a complex, regulated process occurring widely throughout nature. Decades ago, its presence in the vasculature was considered a mere curiosity and an unregulated, “dystrophic” process that does not involve biological mechanisms. While it remains controversial whether the process has any adaptive value or past evolutionary advantage, substantial advances have been made in understanding the biological mechanisms driving the process. Different types of calcific vasculopathy, such as inflammatory vs. metabolic, have parallel mechanisms in skeletal bone calcification, such as intramembranous and endochondral ossification. Recent work has identified important regulatory roles for inflammation, oxidized lipids, elastin, alkaline phosphatase, osteoprogenitor cells, matrix gamma-carboxyglutamic acid protein (MGP), transglutaminase, osteoclastic regulatory factors, phosphate regulatory hormones and receptors, apoptosis, prelamin A, autophagy, and microvesicles or microparticles similar to the matrix vesicles of skeletal bone. Recent work has uncovered fascinating interactions between MGP, vitamin K, warfarin and transport proteins. And, lastly, recent breakthroughs in inherited forms of calcific vasculopathy, have identified the genes responsible as well as an unexpected overlap of phenotypes. PMID:24665125

Autophagy inhibitor 3-methyladenine protects against endothelial cell barrier dysfunction in acute lung injury.

PubMed

Slavin, Spencer A; Leonard, Antony; Grose, Valerie; Fazal, Fabeha; Rahman, Arshad

2018-03-01

Autophagy is an evolutionarily conserved cellular process that facilitates the continuous recycling of intracellular components (organelles and proteins) and provides an alternative source of energy when nutrients are scarce. Recent studies have implicated autophagy in many disorders, including pulmonary diseases. However, the role of autophagy in endothelial cell (EC) barrier dysfunction and its relevance in the context of acute lung injury (ALI) remain uncertain. Here, we provide evidence that autophagy is a critical component of EC barrier disruption in ALI. Using an aerosolized bacterial lipopolysaccharide (LPS) inhalation mouse model of ALI, we found that administration of the autophagy inhibitor 3-methyladenine (3-MA), either prophylactically or therapeutically, markedly reduced lung vascular leakage and tissue edema. 3-MA was also effective in reducing the levels of proinflammatory mediators and lung neutrophil sequestration induced by LPS. To test the possibility that autophagy in EC could contribute to lung vascular injury, we addressed its role in the mechanism of EC barrier disruption. Knockdown of ATG5, an essential regulator of autophagy, attenuated thrombin-induced EC barrier disruption, confirming the involvement of autophagy in the response. Similarly, exposure of cells to 3-MA, either before or after thrombin, protected against EC barrier dysfunction by inhibiting the cleavage and loss of vascular endothelial cadherin at adherens junctions, as well as formation of actin stress fibers. 3-MA also reversed LPS-induced EC barrier disruption. Together, these data imply a role of autophagy in lung vascular injury and reveal the protective and therapeutic utility of 3-MA against ALI.

The presence of pleiotrophin in the human intervertebral disc is associated with increased vascularization: an immunohistologic study.

PubMed

Johnson, William E B; Patterson, Angela M; Eisenstein, Stephen M; Roberts, Sally

2007-05-20

An immunohistological study of surgical specimens of human intervertebral disc. To examine the presence of pleiotrophin in diseased or damaged intervertebral disc tissue and the association between its presence and the extent of tissue vascularization and innervation. Increased levels of pleiotrophin, a growth and differentiation factor that is active in various pathophysiologic processes, including angiogenesis, has been associated with osteoarthritic changes of human articular cartilage. The association between pleiotrophin expression and pathologic conditions of the human intervertebral disc is unknown. Specimens of human lumbar intervertebral discs, obtained following surgical discectomy, were divided into 3 groups: non-degenerated discs (n = 7), degenerated discs (n = 6), and prolapsed discs (n = 11). Serial tissue sections of each specimen were immunostained to determine the presence of pleiotrophin, blood vessels (CD34-positive endothelial cells), and nerves (neurofilament 200 kDa [NF200]-positive nerve fibers). Pleiotrophin immunoreactivity was seen in disc cells, endothelial cells, and in the extracellular matrix in most specimens of intervertebral disc but was most prevalent in vascularized tissue in prolapsed discs. There was a significant correlation between the presence of pleiotrophin-positive disc cells and that of CD34-positive blood vessels. NF200-positive nerves were seen in vascularized areas of more degenerated discs, but nerves did not appear to codistribute with blood vessels or pleiotrophin positivity in prolapsed discs. Pleiotrophin is present in pathologic human intervertebral discs, and its prevalence and distribution suggest that it may play a role in neovascularization of diseased or damaged disc tissue.

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

Quality and Safety in Health Care, Part XXI: PSOs and the Vascular Quality Initiative.

PubMed

Harolds, Jay A

2017-04-01

Congress provided for the formation of patient safety organizations (PSOs) so that physicians and other providers would come forward to improve the safety and quality of health care. Important legal safeguards for the providers and patients were put in place for PSOs. The Society for Vascular Surgery (SVS) PSO operates the Vascular Quality Initiative. The latter gathers information from certain commonly done vascular procedures. First, information is collected so a risk adjustment determination of each individual patient can be done. Then the details of every procedure are recorded for later analysis of the processes of the patient's care. In addition, outcome analysis from all procedures is carried out. This registry is an important source of data for research improving health care safety and quality.

Relationship between Serum Uric Acid and Vascular Function and Structure Markers and Gender Difference in a Real-World Population of China-From Beijing Vascular Disease Patients Evaluation Study (BEST) Study.

PubMed

Liu, Huan; Liu, Jinbo; Zhao, Hongwei; Zhou, Yingyan; Li, Lihong; Wang, Hongyu

2018-03-01

The study was done to establish the relationship between serum uric acid (UA) and vascular function and structure parameters including carotid femoral pulse wave velocity (CF-PWV), carotid radial pulse wave velocity (CR-PWV), cardio ankle vascular index (CAVI), ankle brachial index (ABI), and carotid intima-media thickness (CIMT), and the gender difference in a real-world population from China. A total of 979 subjects were enrolled (aged 60.86±11.03 years, male 416 and female 563). Value of UA was divided by 100 (UA/100) for analysis. Body mass index (BMI), diastolic blood pressure (DBP), fasting plasma glucose (FPG), UA, and UA/100 were significantly higher in males compared with females (all p＜0.05); pulse pressure (PP), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were lower in males than females (all p＜0.05). All vascular parameters including CF-PWV, CR-PWV, CAVI, ABI, and CIMT were higher in males than females (all p＜0.05). Multiple linear regression analysis showed that UA/100 was independently positively linearly correlated with CAVI (B=0.143, p=0.001) and negatively correlated with ABI in the male population (B=－0.012, p=0.020). In people with higher UA, the risk of higher CF-PWV was 1.593 (p＜0.05). 1. All vascular parameters were higher in males than females. There was no gender difference in the relationship between UA and vascular markers except in ABI. 2. UA was independently linearly correlated with CAVI. 3. In people with higher UA level, the risk of higher CF-PWV increased. Therefore, higher UA may influence the vascular function mainly instead of vascular structure.

A checklist of the vascular plants in Abbott Creek Research Natural Area, Oregon.

Treesearch

Rod Mitchell

1979-01-01

This paper is a checklist of 277 vascular plant taxa that have been collected or encountered in Abbott Creek Research Natural Area, Oregon; a brief description of five forested and two nonforested vegetation types is included.

Molecular and cellular mechanisms of aortic stenosis.

PubMed

Yetkin, Ertan; Waltenberger, Johannes

2009-06-12

Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

An Effective Histological Staining Process to Visualize Bone Interstitial Fluid Space Using Confocal Microscopy

PubMed Central

Ciani, Cesare; Doty, Stephen B.; Fritton, Susannah P.

2009-01-01

Bone is a composite porous material with two functional levels of porosity: the vascular porosity that surrounds blood vessels and the lacunar-canalicular porosity that surrounds the osteocytes. Both the vascular porosity and lacunar-canalicular porosity are directly involved in interstitial fluid flow, thought to play an important role in bone’s maintenance. Because of the small dimensions of the lacunar-canalicular porosity, interstitial fluid space has been difficult to visualize and quantify. We report a new staining protocol that is reliable and easily reproducible, using fluorescein isothiocyanate (FITC) as a probe visualized by confocal microscopy. Reconstructed FITC-stained cross sections enable effective visualization of bone microstructure and microporosities. This new staining process can be used to analyze interstitial fluid space, providing high-resolution quantification of the vascular pores and the lacunar-canalicular network of cortical and cancellous bone. PMID:19442607

The Science of Stroke: Mechanisms in Search of Treatments

PubMed Central

Moskowitz, Michael A.; Lo, Eng H.; Iadecola, Costantino

2010-01-01

Summary This review focuses on mechanisms and emerging concepts that drive the science of stroke in a therapeutic direction. Once considered exclusively a disorder of blood vessels, growing evidence has led to the realization that the biological processes underlying stroke are driven by the interaction of neurons, glia, vascular cells and matrix components, which actively participate in mechanisms of tissue injury and repair. As new targets are identified, new opportunities emerge that build on an appreciation of acute cellular events acting in a broader context of ongoing destructive, protective and reparative processes. The burden of disease is great and its magnitude widens as a role for blood vessels and stroke in vascular and non-vascular dementias becomes more clearly established. This review then poses a number of fundamental questions, the answers to which may generate new directions for research and possibly new treatments that could reduce the impact of this enormous economic and societal burden. PMID:20670828

NORMALIZATION OF THE VASCULATURE FOR TREATMENT OF CANCER AND OTHER DISEASES

PubMed Central

Goel, Shom; Duda, Dan G.; Xu, Lei; Munn, Lance L.; Boucher, Yves; Fukumura, Dai; Jain, Rakesh K.

2012-01-01

New vessel formation (angiogenesis) is an essential physiological process for embryologic development, normal growth, and tissue repair. Angiogenesis is tightly regulated at the molecular level. Dysregulation of angiogenesis occurs in various pathologies and is one of the hallmarks of cancer. The imbalance of pro- and anti-angiogenic signaling within tumors creates an abnormal vascular network that is characterized by dilated, tortuous, and hyperpermeable vessels. The physiological consequences of these vascular abnormalities include temporal and spatial heterogeneity in tumor blood flow and oxygenation and increased tumor interstitial fluid pressure. These abnormalities and the resultant microenvironment fuel tumor progression, and also lead to a reduction in the efficacy of chemotherapy, radiotherapy, and immunotherapy. With the discovery of vascular endothelial growth factor (VEGF) as a major driver of tumor angiogenesis, efforts have focused on novel therapeutics aimed at inhibiting VEGF activity, with the goal of regressing tumors by starvation. Unfortunately, clinical trials of anti-VEGF monotherapy in patients with solid tumors have been largely negative. Intriguingly, the combination of anti-VEGF therapy with conventional chemotherapy has improved survival in cancer patients compared with chemotherapy alone. These seemingly paradoxical results could be explained by a “normalization” of the tumor vasculature by anti-VEGF therapy. Preclinical studies have shown that anti-VEGF therapy changes tumor vasculature towards a more “mature” or “normal” phenotype. This “vascular normalization” is characterized by attenuation of hyperpermeability, increased vascular pericyte coverage, a more normal basement membrane, and a resultant reduction in tumor hypoxia and interstitial fluid pressure. These in turn can lead to an improvement in the metabolic profile of the tumor microenvironment, the delivery and efficacy of exogenously administered therapeutics, the efficacy of radiotherapy and of effector immune cells, and a reduction in number of metastatic cells shed by tumors into circulation in mice. These findings are consistent with data from clinical trials of anti-VEGF agents in patients with various solid tumors. More recently, genetic and pharmacological approaches have begun to unravel some other key regulators of vascular normalization such as proteins that regulate tissue oxygen sensing (PHD2) and vessel maturation (PDGFRβ, RGS5, Ang1/2, TGF-β). Here, we review the pathophysiology of tumor angiogenesis, the molecular underpinnings and functional consequences of vascular normalization, and the implications for treatment of cancer and nonmalignant diseases. PMID:21742796

Neural guidance molecules regulate vascular remodeling and vessel navigation.

PubMed

Eichmann, Anne; Makinen, Taija; Alitalo, Kari

2005-05-01

The development of the embryonic blood vascular and lymphatic systems requires the coordinated action of several transcription factors and growth factors that target endothelial and periendothelial cells. However, according to recent studies, the precise "wiring" of the vascular system does not occur without an ordered series of guidance decisions involving several molecules initially discovered for axons in the nervous system, including ephrins, netrins, slits, and semaphorins. Here, we summarize the new advances in our understanding of the roles of these axonal pathfinding molecules in vascular remodeling and vessel guidance, indicating that neuronal axons and vessel sprouts use common molecular mechanisms for navigation in the body.

Neurocognitive differential diagnosis of dementing diseases: Alzheimer's Dementia, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder.

PubMed

Braaten, Alyssa J; Parsons, Thomas D; McCue, Robert; Sellers, Alfred; Burns, William J

2006-11-01

Similarities in presentation of Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder, pose differential diagnosis challenges. The current study identifies specific neuropsychological patterns of scores for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. Neuropsychological domains directly assessed in the study included: immediate memory, delayed memory, confrontational naming, verbal fluency, attention, concentration, and executive functioning. The results reveal specific neuropsychological comparative profiles for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. The identification of these profiles will assist in the differential diagnosis of these disorders and aid in patient treatment.

A vascular disease educational program in the preclinical years of medical school increases student interest in vascular disease.

PubMed

Godshall, Christopher J; Moore, Phillip S; Fleming, Shawn H; Andrews, Jeanette S; Hansen, Kimberley J; Hoyle, John R; Edwards, Matthew S

2010-09-01

New training paradigms in vascular surgery necessitate medical student interest in vascular disease. We examined the effects of incorporation of a vascular disease educational program during the second year of the medical school curriculum on student acquisition of knowledge and interest in the treatment of vascular disease. We developed and administered a new educational program on vascular disease and delivered the program to all second-year medical students. The new program encompassed 9 didactic hours, including 7 traditional lecture hours and 2 hours of problem-based learning. After completing the program, students were surveyed regarding vascular disease-specific knowledge, interest in treating vascular disease, and career choices. Third-year students who were not exposed to the program were surveyed as a control group. We recorded the voluntary student enrollment in the vascular and endovascular surgery rotation during the following academic year. Voluntary enrollment of the students exposed to the vascular disease education program was compared with enrollment for the previous 8 years. Before the introduction of the new educational program, 946 total lecture hours were delivered to first- and second-year medical students, comprising 490 hours (52%) given by nonsurgeon physicians, 445 (47%) by nonphysicians, and 11 (1%) by surgeons. Survey response rate was 93% (112 of 121) for second-year students and 95% (39 of 41) for third-year students. After the vascular disease program, second-year students answered 7.1 +/- 1.4 of 9 vascular disease questions correctly, whereas unexposed third-year students answered 7.2 +/- 1.7 questions correctly (P = .96). Most second-year medical students described a "somewhat" or "much greater" interest in the medical (63%), procedural (59%), and overall (63%) management of vascular disease after exposure to the program. Most also had a "somewhat" or "much greater" interest in a vascular medicine (64%) or vascular and endovascular surgery (60%) rotation. Enrollment in the vascular surgery third-year clerkship increased significantly to a mean of 3.0 students/month from 1.16 students/month in the prior year (P = .0032, postintervention year vs 8 prior years). A vascular disease educational program administered to second-year medical students increases interest in vascular disease and interest in further training. The increased interest translates to greater student enrollment in the vascular surgery clerkship in the subsequent academic year.

Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and meta-analysis.

PubMed

Clark, Christopher E; Taylor, Rod S; Shore, Angela C; Ukoumunne, Obioha C; Campbell, John L

2012-03-10

Differences in systolic blood pressure (SBP) of 10 mm Hg or more or 15 mm Hg or more between arms have been associated with peripheral vascular disease and attributed to subclavian stenosis. We investigated whether an association exists between this difference and central or peripheral vascular disease, and mortality. We searched Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, and Medline In Process databases for studies published before July, 2011, showing differences in SBP between arms, with data for subclavian stenosis, peripheral vascular disease, cerebrovascular disease, cardiovascular disease, or survival. We used random effects meta-analysis to combine estimates of the association between differences in SBP between arms and each outcome. We identified 28 eligible studies for review, 20 of which were included in our meta-analyses. In five invasive studies using angiography, mean difference in SBP between arms was 36·9 mm Hg (95% CI 35·4-38·4) for proven subclavian stenosis (>50% occlusion), and a difference of 10 mm Hg or more was strongly associated with subclavian stenosis (risk ratio [RR] 8·8, 95% CI 3·6-21·2). In non-invasive studies, pooled findings showed that a difference of 15 mm Hg or more was associated with peripheral vascular disease (nine cohorts; RR 2·5, 95% CI 1·6-3·8; sensitivity 15%, 9-23; specificity 96%, 94-98); pre-existing cerebrovascular disease (five cohorts; RR 1·6, 1·1-2·4; sensitivity 8%, 2-26; specificity 93%, 86-97); and increased cardiovascular mortality (four cohorts; hazard ratio [HR] 1·7, 95% CI 1·1-2·5) and all-cause mortality (HR 1·6, 1·1-2·3). A difference of 10 mm Hg or higher was associated with peripheral vascular disease (five studies; RR 2·4, 1·5-3·9; sensitivity 32%, 23-41; specificity 91%, 86-94). A difference in SBP of 10 mm Hg or more, or of 15 mm Hg or more, between arms might help to identify patients who need further vascular assessment. A difference of 15 mm Hg or more could be a useful indicator of risk of vascular disease and death. Royal College of General Practitioners, South West GP Trust, and Peninsula Collaboration for Leadership in Applied Health Research and Care. Copyright © 2012 Elsevier Ltd. All rights reserved.

Using NASA's GeneLab for VESGEN Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, P.; Weitzel, Alexander; Vyas, R. J.; Murray, M. C.; Vickerman, M. B.; Bhattacharya, S.; Wyatt, S. E.

2016-01-01

One fundamental requirement shared by humans with all higher terrestrial life forms, including other vertebrates, insects, and higher land plants, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. A unifying perspective is that vascular patterning offers a useful readout of molecular signaling that necessarily integrates these complex pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascularrelated changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the spatial and dynamic dimensions of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions. Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a Notch antagonist were analyzed by VESGEN. Other VESGEN research applications include the mouse retina, GI and coronary vessels, avian placental analogs and translational studies in the astronaut retina related to health challenges for long-duration missions.

Numerical models of cell death in RF ablation with monopolar and bipolar probes

NASA Astrophysics Data System (ADS)

Bright, Benjamin M.; Pearce, John A.

2013-02-01

Radio frequency (RF) is used clinically to treat unresectible tumors. Finite element modeling has proven useful in treatment planning and applicator design. Typically isotherms in the middle 50s °C have been used as the parameter of assessment in these models. We compare and contrast isotherms for multiple known Arrhenius thermal damage predictors including collagen denaturation, vascular disruption, liver coagulation and cell death. Models for RITA probe geometries are included in the study. Comparison to isotherms is sensible when the activation time is held constant, but varies considerably when heating times vary. The purpose of this paper is to demonstrate the importance of looking at specific processes and keeping track of the methods used to derive the Arrhenius coefficients in order to study the extremely complex cell death processes due to thermal therapies.

Patients with advanced Parkinson's disease with and without freezing of gait: a comparative analysis of vascular lesions using brain MRI.

PubMed

Gallardo, M J; Cabello, J P; Pastor, C; Muñoz-Torrero, J J; Carrasco, S; Ibañez, R; Vaamonde, J

2014-05-01

Freezing of gait (FOG) is one of the most disabling and enigmatic symptoms in Parkinson's disease. Vascular lesions, observed in magnetic resonance imaging (MRI) scans, may produce or exacerbate this symptom. The study includes 22 patients with Parkinson's disease subjects, 12 with freezing of gait and 10 without. All patients underwent an MRI scan and any vascular lesions were analysed using the modified Fazekas scale. Patients with FOG scored higher on the modified Fazekas scale than the rest of the group. Although the two groups contained the same percentage of patients with vascular lesions (50% in both groups), lesion load was higher in the group of patients with FOG. Vascular lesions in the periventricular area and deep white matter seem to be the most involved in the development of FOG. Vascular lesions may contribute to the onset or worsening of FOG in patients with PD. This study suggests that cerebral vascular disease should be considered in patients with FOG. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Sleep apnoea and stroke

PubMed Central

Sharma, Sameer; Culebras, Antonio

2016-01-01

Sleep disorders have been known to physicians for a long time. In his famous aphorisms, Hippocrates said “Sleep or watchfulness exceeding that which is customary, augurs unfavorably”. Modern medicine has been able to disentangle some of the phenomena that disturb sleep. Among the most notable offenders is sleep apnoea that has gained prominence in the past few decades. It is being proposed as one of the potentially modifiable risk factors for vascular diseases including stroke. The pathological mechanisms linking sleep apnoea to vascular risk factors include hypoxia, cardiac arrhythmias, dysautonomia, impaired glucose tolerance, hypertension, dyslipidaemia and inflammation. In this article, we review literature linking sleep apnoea and stroke, including sleep apnoea as a risk factor for primary prevention with the potential to improve outcome after acute stroke and as a secondary risk factor, amenable to modification and hence vascular risk reduction. PMID:28959482

Nuclear Localization of Vascular Endothelial Growth Factor-D and Regulation of c-Myc–Dependent Transcripts in Human Lung Fibroblasts

PubMed Central

Pacheco-Rodriguez, Gustavo; Malide, Daniela; Meza-Carmen, Victor; Kato, Jiro; Cui, Ye; Padilla, Philip I.; Samidurai, Arun; Gochuico, Bernadette R.

2014-01-01

Lymphangiogenesis and angiogenesis are processes that are, in part, regulated by vascular endothelial growth factor (VEGF)-D. The formation of lymphatic structures has been implicated in multiple lung diseases, including pulmonary fibrosis. VEGF-D is a secreted protein produced by fibroblasts and macrophages, which induces lymphangiogenesis by signaling via VEGF receptor-3, and angiogenesis through VEGF receptor-2. VEGF-D contains a central VEGF homology domain, which is the biologically active domain, with flanking N- and C-terminal propeptides. Full-length VEGF-D (∼ 50 kD) is proteolytically processed in the extracellular space, to generate VEGF homology domain that contains the VEGF-D receptor–binding sites. Here, we report that, independent of its cell surface receptors, full-length VEGF-D accumulated in nuclei of fibroblasts, and that this process appears to increase with cell density. In nuclei, full-length VEGF-D associated with RNA polymerase II and c-Myc. In cells depleted of VEGF-D, the transcriptionally regulated genes appear to be modulated by c-Myc. These findings have potential clinical implications, as VEGF-D was found in fibroblast nuclei in idiopathic pulmonary fibrosis, a disease characterized by fibroblast proliferation. These findings are consistent with actions of full-length VEGF-D in cellular homeostasis in health and disease, independent of its receptors. PMID:24450584

Transient Receptor Potential Channels in the Vasculature

PubMed Central

Earley, Scott; Brayden, Joseph E.

2015-01-01

The mammalian genome encodes 28 distinct members of the transient receptor potential (TRP) superfamily of cation channels, which exhibit varying degrees of selectivity for different ionic species. Multiple TRP channels are present in all cells and are involved in diverse aspects of cellular function, including sensory perception and signal transduction. Notably, TRP channels are involved in regulating vascular function and pathophysiology, the focus of this review. TRP channels in vascular smooth muscle cells participate in regulating contractility and proliferation, whereas endothelial TRP channel activity is an important contributor to endothelium-dependent vasodilation, vascular wall permeability, and angiogenesis. TRP channels are also present in perivascular sensory neurons and astrocytic endfeet proximal to cerebral arterioles, where they participate in the regulation of vascular tone. Almost all of these functions are mediated by changes in global intracellular Ca2+ levels or subcellular Ca2+ signaling events. In addition to directly mediating Ca2+ entry, TRP channels influence intracellular Ca2+ dynamics through membrane depolarization associated with the influx of cations or through receptor- or store-operated mechanisms. Dysregulation of TRP channels is associated with vascular-related pathologies, including hypertension, neointimal injury, ischemia-reperfusion injury, pulmonary edema, and neurogenic inflammation. In this review, we briefly consider general aspects of TRP channel biology and provide an in-depth discussion of the functions of TRP channels in vascular smooth muscle cells, endothelial cells, and perivascular cells under normal and pathophysiological conditions. PMID:25834234

Multisociety consensus quality improvement guidelines for intraarterial catheter-directed treatment of acute ischemic stroke, from the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, European Society of Minimally Invasive Neurological Therapy, and Society of Vascular and Interventional Neurology.

PubMed

Sacks, David; Black, Carl M; Cognard, Christophe; Connors, John J; Frei, Donald; Gupta, Rishi; Jovin, Tudor G; Kluck, Bryan; Meyers, Philip M; Murphy, Kieran J; Ramee, Stephen; Rüfenacht, Daniel A; Bernadette Stallmeyer, M J; Vorwerk, Dierk

2013-02-01

In this international multispecialty document, quality benchmarks for processes of care and clinical outcomes are defined. It is intended that these benchmarks be used in a quality assurance program to assess and improve processes and outcomes in acute stroke revascularization. Members of the writing group were appointed by the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society of Cardiac Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, European Society of Minimally Invasive Neurological Therapy, and Society of Vascular and Interventional Neurology. The writing group reviewed the relevant literature from 1986 through February 2012 to create an evidence table summarizing processes and outcomes of care. Performance metrics and thresholds were then created by consensus. The guideline was approved by the sponsoring societies. It is intended that this guideline be fully updated in 3 years. In this international multispecialty document, quality benchmarks for processes of care and clinical outcomes are defined. These include process measures of time to imaging, arterial puncture, and revascularization and measures of clinical outcome up to 90 days. Quality improvement guidelines are provided for endovascular acute ischemic stroke revascularization procedures. Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.

[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.

Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

PubMed Central

Forte, Maurizio; Damato, Antonio; Ambrosio, Mariateresa; Puca, Annibale A.; Sciarretta, Sebastiano; Frati, Giacomo; Vecchione, Carmine

2016-01-01

Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases. PMID:27651855

Fibroblast Growth Factors and Vascular Endothelial Growth Factor Promote Cardiac Reprogramming under Defined Conditions.

PubMed

Yamakawa, Hiroyuki; Muraoka, Naoto; Miyamoto, Kazutaka; Sadahiro, Taketaro; Isomi, Mari; Haginiwa, Sho; Kojima, Hidenori; Umei, Tomohiko; Akiyama, Mizuha; Kuishi, Yuki; Kurokawa, Junko; Furukawa, Tetsushi; Fukuda, Keiichi; Ieda, Masaki

2015-12-08

Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF) 2, FGF10, and vascular endothelial growth factor (VEGF), termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Recombinant Domain V of Human Perlecan Is a Bioactive Vascular Proteoglycan.

PubMed

Rnjak-Kovacina, Jelena; Tang, Fengying; Lin, Xiaoting; Whitelock, John M; Lord, Megan S

2017-12-01

The C-terminal domain V of the extracellular matrix proteoglycan perlecan plays unique and often divergent roles in a number of biological processes, including angiogenesis, vascular cell interactions, wound healing, and autophagy. Recombinant forms of domain V have been proposed as therapeutic agents for the treatment of cancer, stroke, and the development of cardiovascular devices and bioartificial tissues. However, the effect of domain V appears to be related to the differences in domain V structure and function observed in different expression systems and environments and exactly how this occurs is not well understood. In this study, the sequence from amino acid 3626 to 4391 of the perlecan protein core, which includes domain V, is expressed in HEK-293 cells and purified as a secreted product from conditioned media. This recombinant domain V (rDV) is expressed as a proteoglycan decorated with heparan sulfate and chondroitin sulfate chains and supports endothelial cell interactions to the same extent as full-length perlecan. This expression system serves as an important model of recombinant proteoglycan expression, as well as a source of biologically active rDV for therapeutic applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Feasibility of a Structured Cognitive Training Protocol to Address Progressive Cognitive Decline in Individuals with Vascular Dementia

ERIC Educational Resources Information Center

Mayer, Jamie F.; Bishop, Lilli A.; Murray, Laura L.

2012-01-01

Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, better known as CADASIL, is a rare, genetic form of early-onset vascular dementia. The purpose of this study was to use a modified version of Attention Process Training--II (APT-II; Sohlberg, Johnson, Paule, Raskin, & Mateer, 2001) with an…

Vascular Procr+ stem cells: Finding new branches while looking for the roots.

PubMed

Gur-Cohen, Shiri; Lapidot, Tsvee

2016-10-01

Generation and growth of the blood vasculature network is a highly synchronized process, requiring coordinated efforts of endothelial cells and pericytes to maintain blood vessel integrity and regeneration. In a recent paper published in Cell Research, Yu et al. identified and characterized bipotent Procr-expressing vascular endothelial stem cells, which give rise to both endothelial cells and pericytes.

The Decay of Stem Cell Nourishment at the Niche

PubMed Central

de Mora, Jaime Font

2013-01-01

Abstract One of the main features of human aging is the loss of adult stem cell homeostasis. Organs that are very dependent on adult stem cells show increased susceptibility to aging, particularly organs that present a vascular stem cell niche. Reduced regenerative capacity in tissues correlates with reduced stem cell function, which parallels a loss of microvascular density (rarefraction) and plasticity. Moreover, the age-related loss of microvascular plasticity and rarefaction has significance beyond metabolic support for tissues because stem cell niches are regulated co-ordinately with the vascular cells. In addition, microvascular rarefaction is related to increased inflammatory signals that may negatively regulate the stem cell population. Thus, the processes of microvascular rarefaction, adult stem cell dysfunction, and inflammation underlie the cycle of physiological decline that we call aging. Observations from new mouse models and humans are discussed here to support the vascular aging theory. We develop a novel theory to explain the complexity of aging in mammals and perhaps in other organisms. The connection between vascular endothelial tissue and organismal aging provides a potential evolutionary conserved mechanism that is an ideal target for the development of therapies to prevent or delay age-related processes in humans. PMID:23937078

The Unfolded Protein Response in Retinal Vascular Diseases: Implications and Therapeutic Potential Beyond Protein Folding

PubMed Central

Zhang, Sarah X.; Ma, Jacey H.; Bhatta, Maulasri; Fliesler, Steven J.; Wang, Joshua J.

2015-01-01

Angiogenesis is a complex, step-wise process of new vessel formation that is involved in both normal embryonic development as well as postnatal pathological processes, such as cancer, cardiovascular disease, and diabetes. Aberrant blood vessel growth, also known as neovascularization, in the retina and the choroid is a major cause of vision loss in severe eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and central and branch retinal vein occlusion. Yet, retinal neovascularization is causally and dynamically associated with vasodegeneration, ischemia, and vascular remodeling in retinal tissues. Understanding the mechanisms of retinal neovascularization is an urgent unmet need for developing new treatments for these devastating diseases. Accumulating evidence suggests a vital role for the unfolded protein response (UPR) in regulation of angiogenesis, in part through coordinating the secretion of pro-angiogenic growth factors, such as VEGF, and modulating endothelial cell survival and activity. Herein, we summarize current research in the context of endoplasmic reticulum (ER) stress and UPR signaling in retinal angiogenesis and vascular remodeling, highlighting potential implications of targeting these stress response pathways in the prevention and treatment of retinal vascular diseases that result in visual deficits and blindness. PMID:25529848

(18)F-sodium fluoride PET/CT for the in vivo visualization of Mönckeberg's sclerosis in a diabetic patient.

PubMed

Quirce, R; Martínez-Rodríguez, I; Banzo, I; de Arcocha-Torres, M; Jiménez-Bonilla, J F; Martínez-Amador, N; Ibáñez-Bravo, S; Ramos, L; Amado, J A; Carril, J M

2015-01-01

Diabetes is a major frequent cause of atherosclerosis vascular disease. Arterial calcification in diabetic patients is responsible for peripheral vascular involvement. Molecular imaging using (18)F-sodium fluoride ((18)F-NaF) positron emission tomography (PET)/computed tomography (CT) has been recently proposed as a marker to study the in vivo mineralization process in the atheroma plaque. A 69-year-old man with a history of type 2 diabetes and no clinical evidence of peripheral arterial disease underwent an (18)F-NaF PET/CT scan. A linear, well-defined (18)F-NaF uptake was detected along the femoral arteries. In addition, the CT component of the PET/CT identified an unsuspected "tram-track" calcification in his femoral arteries, suggestive of medial calcification (Mönckeberg's sclerosis). In other vascular territories, focal (18)F-NaF uptake was also detected in carotid and aorta atheroma plaques. Molecular imaging with (18)F-NaF PET/CT might provide new functional information about the in vivo vascular calcification process in diabetic patients. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

The pathology and pathophysiology of vascular dementia.

PubMed

Kalaria, Raj N

2017-12-19

Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Clinical Picture. The Eyes: A Window into the Past

DTIC Science & Technology

2010-07-01

disseminated histoplasmosis, eye in- volvement manifests as panophthalmitis or uveitis , caused by yeast implantation. The finding of eye lesions typical of...Amsler grid.11 For POHS with choroidal neo- vascularization, treatment focuses on reducing the risk of vascular complications and includes oral...Antifungal treatment is not use- ful, as the lesions are not proven to be caused by active infection.10 Future treatments may include antiangio- genic drugs

The epidemiology of vascular injury in the wars in Iraq and Afghanistan.

PubMed

White, Joseph M; Stannard, Adam; Burkhardt, Gabriel E; Eastridge, Brian J; Blackbourne, Lorne H; Rasmussen, Todd E

2011-06-01

Blood vessel trauma leading to hemorrhage or ischemia presents a significant cause of morbidity and mortality after battlefield injury. The objective of this study is to characterize the epidemiology of vascular injury in the wars of Iraq and Afghanistan, including categorization of anatomic patterns, mechanism, and management of casualties. The Joint Theater Trauma Registry was interrogated (2002-2009) for vascular injury in US troops to identify specific injury (group 1) and operative intervention (group 2) groups. Battle-related injuries (nonreturn to duty) were used as the denominator to establish injury rates. Mechanism of injury was compared between theaters of war and the management strategies of ligation versus revascularization (repair and interposition grafting) reported. Group 1 included 1570 Troops injured in Iraq (OIF) (n = 1390) and Afghanistan (OEF) (n = 180). Mechanism included explosive (73%), gunshot (27%), and other (<1%) with explosive more common in OIF than OEF (P < 0.05). During this period, 13,076 battle-related injuries occurred resulting in a specific rate of 12% (1570 of 13,076), which was higher in OIF than OEF (12.5% vs 9% respectively; P < 0.05). Of group 1, 60% (n = 940) sustained injury to major or proximal vessels and 40% (n = 630) to minor or distal vessels (unknown vessel, n = 27). Group 2 (operative) comprised 1212 troops defining an operative rate of 9% (1212 of 13,076) and included ligation (n = 660; 54%) or repair (n = 552; 46%). Peak rates in OIF and OEF occurred in November 2004 (15%) and August 2009 (11%), respectively and correlated with combat operational tempo. The rate of vascular injury in modern combat is 5 times that reported in previous wars and varies according to theater of war, mechanism of injury and operational tempo. Methods of reconstruction are now applied to nearly half of the vascular injuries and should be a focus of training for combat surgery. Selective ligation of vascular injury remains an important management strategy, especially for minor or distal vessel injuries.

The potential relationship between Flammer and Sjögren syndromes: the chime of dysfunction.

PubMed

Baban, Babak; Golubnitschaja, Olga

2017-12-01

Flammer syndrome (FS) is a term to blanket a cluster of vascular and nonvascular signs and symptoms linked to primary vascular dysregulation (PVD), increased sensitivity to various stimuli (stress, drugs, etc.) and altered sense regulation such as pain, smell and thirst perception. On one hand, disruption of blood barrier and homeostasis of the body are the main targets of vascular irregularity. Inflammation and immune disorders including autoimmunity are considered as a consequence of the abnormal vascular regulation processes. On the other hand, decreased thirst feeling typical for FS-affected individuals may lead to extensive body dehydration resulting in dry eye appearance and breast cancer (BC) risk, amongst others. To this end, recent research demonstrated FS as linked to BC development and progression into the metastatic disease. On the other side, Sjögren syndrome (SS) is an autoimmune disease characterised by a progressive sicca syndrome associated with the dry eye symptoms, specific immunologic complex and/or significant infiltrate at minor salivary gland biopsy. SS is relatively frequent, with a clinical diagnosis predominantly amongst women. Its physiopathology is a complex battery of both environmental and genetic factors. If left untreated, SS may be associated with and/or resulted in severe arthritis and the development of B cell lymphoma. In this mini-review, we summarise the facts and hypotheses connecting FS and SS symptoms together and mechanisms potentially overlapping in both syndromes. Unraveling the common denominators between these two syndromes not only providing more evidence for interaction between altered sense regulation, vascular dysregulation, immune system dysfunction but also focusing on the individual outcomes in terms of severity grade and potential complications exploring novel diagnostic, prognostic and treatment modalities. Multi-professional considerations presented here are an example how to effectively enter the new era of preventive, predictive and personalised medicine benefiting the patients and healthcare system as the whole.

Vascular labeling of the head and neck vessels: Technique, advantages and limitations.

PubMed

Gálvez, Alba; Caraballo, José-Leonardo; Manzanares-Céspedes, María-Cristina; Valdivia-Gandur, Iván; Figueiredo, Rui; Valmaseda-Castellón, Eduard

2017-05-01

Vascular staining techniques have been used to describe the vascular structures of several anatomic areas. However, few reports have described this procedure in the head and neck region. This paper describes a head and neck vascular labeling procedure, and describes some of the technical complications that may occur. Fifteen specimen cadaver heads were prepared. After drying the vascular system, the internal carotid arteries were ligated and a solution with latex and a gelling agent was injected into the internal carotid arteries and external jugular veins. Two different colors were employed to differentiate arteries from veins. A total of 60ml latex was injected into each blood vessel. Subsequently, the specimens were refrigerated at 5°C for a minimum of 24 hours. Finally, a dissection was performed to identify the venous and arterial systems of the maxillofacial region. In most specimens, correct identification of the vascular structures (lingual artery, pterigoyd plexus, and the major palatal arteries, among others) was possible. However, in three heads a major technical problem occurred (the latex remained liquid), making the dissection unfeasible. Other minor complications such as latex obstruction due to the presence of atheromas were found in two further specimens. The vascular labeling technique is a predictable, effective and simple method for analyzing the vascular system of the maxillofacial area in cadaveric studies, including vessels of reduced diameter or with an intraosseous course. This procedure can be especially useful to teach vascular anatomy to dental students and postgraduate residents. Key words: Blood vessels, vascular casting, vascular labeling, head and neck arteries, carotid arteries, jugular veins.

Contributions of dysglycemia, obesity and insulin resistance to impaired endothelium-dependent vasodilation in humans

PubMed Central

Han, KA; Patel, Y; Lteif, AA; Chisholm, R; Mather, KJ

2011-01-01

Background Individual effects of hyperglycemia and obesity to impair vascular health are recognized. However, the relative contributions of dysglycemia versus other obesity-related traits to vascular dysfunction have not been systematically evaluated. Methods We undertook a cross-sectional evaluation of factors contributing to vascular function in 271 consecutive subjects, categorized as non-obese normal glucose tolerant (n=115), non-obese dysglycemic (n=32), obese normal glucose tolerant (n=57), obese dysglycemic (n=38), or type 2 diabetic (n=29). Vascular function was measured invasively as leg blood flow responses to methacholine chloride, an endothelium-dependent vasodilator. Categorical and continuous analyses were used to assess the contributions of hyperglycemia to vascular dysfunction. Results Even among normoglycemic subjects, obese subjects had impaired vascular function compared to non-obese subjects (p=0.004). Vascular function was also impaired in non-obese dysglycemic subjects (p=0.04 versus non-obese normoglycemic subjects), to a level comparable to normoglycemic obese subjects. Within obese subject groups, gradations of dysglycemia including the presence of diabetes were not associated with further worsening of these vascular responses beyond the effect of obesity alone (p=NS comparing all obese groups, p<0.001 versus lean normoglycemic subjects). In univariate and multivariable modeling analyses we found that effects of glycemia were less powerful than effects of insulin resistance and obesity on vascular dysfunction. Conclusions Dysglycemia contributes to impaired vascular function in non-obese subjects, but obesity and insulin resistance are more important determinants of vascular function in obese and diabetic subjects. PMID:21309061

Cognitive patterns in relation to biomarkers of cerebrovascular disease and vascular risk factors.

PubMed

Miralbell, Júlia; López-Cancio, Elena; López-Oloriz, Jorge; Arenillas, Juan Francisco; Barrios, Maite; Soriano-Raya, Juan José; Galán, Amparo; Cáceres, Cynthia; Alzamora, Maite; Pera, Guillem; Toran, Pere; Dávalos, Antoni; Mataró, Maria

2013-01-01

Risk factors for vascular cognitive impairment (VCI) are the same as traditional risk factors for cerebrovascular disease (CVD). Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. In addition to traditional vascular risk factors (VRF), circulating biomarkers have emerged as potential tools for early diagnoses, as they could provide in vivo measures of the underlying pathophysiology. While VRF have been consistently linked to a VCI profile (i.e., deficits in executive functions and processing speed), the cognitive correlates of CVD biomarkers remain unclear. In this population-based study, the aim was to study and compare cognitive patterns in relation to VRF and circulating biomarkers of CVD. The Barcelona-AsIA Neuropsychology Study included 747 subjects older than 50, without a prior history of stroke or coronary disease and with a moderate to high vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were derived from factoral analysis: visuospatial skills/speed, verbal memory and verbal fluency. Multiple linear regression was used to assess relationships between cognitive performance (multiple domains) and a panel of circulating biomarkers, including indicators of inflammation, C-reactive protein (CRP) and resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA), thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for insulin resistance index). Analyses were adjusted for age, gender, years of education and depressive symptoms. Traditional VRF were related to lower performance in verbal fluency, insulin resistance accounted for lower performance in visuospatial skills/speed and the metabolic syndrome predicted lower performance in both cognitive domains. From the biomarkers of CVD, CRP was negatively related to verbal fluency performance and increasing ADMA levels were associated with lower performance in verbal memory. Resistin and PAI-1 did not relate to cognitive function performance. Vascular risk factors, and markers of inflammation and endothelial dysfunction predicted lower performance in several cognitive domains. Specifically, cognitive functions associated with CRP are typically affected in VCI and overlap those related to VRF. ADMA indicated a dissociation in the cognitive profile involving verbal memory. These findings suggest that inflammation and endothelial dysfunction might play a role in the predementia cognitive impairment stages. Copyright © 2013 S. Karger AG, Basel.

The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design of the Heart-Brain Study

PubMed Central

Hooghiemstra, Astrid M.; Bertens, Anne Suzanne; Leeuwis, Anna E.; Bron, Esther E.; Bots, Michiel L.; Brunner-La Rocca, Hans-Peter; de Craen, Anton J.M.; van der Geest, Rob J.; Greving, Jacoba P.; Kappelle, L. Jaap; Niessen, Wiro J.; van Oostenbrugge, Robert J.; van Osch, Matthias J.P.; de Roos, Albert; van Rossum, Albert C.; Biessels, Geert Jan; van Buchem, Mark A.; Daemen, Mat J.A.P.; van der Flier, Wiesje M.

2017-01-01

Background Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor. PMID:29017156

Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

PubMed

Sun, Miao-Kun

2017-10-16

As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Assessment of placental volume and vascularization at 11-14 weeks of gestation in a Taiwanese population using three-dimensional power Doppler ultrasound.

PubMed

Wang, Hsing-I; Yang, Ming-Jie; Wang, Peng-Hui; Wu, Yi-Cheng; Chen, Chih-Yao

2014-12-01

The placental volume and vascular indices are crucial in helping doctors to evaluate early fetal growth and development. Inadequate placental volume or vascularity might indicate poor fetal growth or gestational complications. This study aimed to evaluate the placental volume and vascular indices during the period of 11-14 weeks of gestation in a Taiwanese population. From June 2006 to September 2009, three-dimensional power Doppler ultrasound was performed in 222 normal pregnancies from 11-14 weeks of gestation. Power Doppler ultrasound was applied to the placenta and the placental volume was obtained by a rotational technique (VOCAL). The three-dimensional power histogram was used to assess the placental vascular indices, including the mean gray value, the vascularization index, the flow index, and the vascularization flow index. The placental vascular indices were then plotted against gestational age (GA) and placental volume. Our results showed that the linear regression equation for placental volume using gestational week as the independent variable was placental volume = 18.852 × GA - 180.89 (r = 0.481, p < 0.05). All the placental vascular indices showed a constant distribution throughout the period 11-14 weeks of gestation. A tendency for a reduction in the placental mean gray value with gestational week was observed, but without statistical significance. All the placental vascular indices estimated by three-dimensional power Doppler ultrasonography showed a constant distribution throughout gestation. Copyright © 2014. Published by Elsevier Taiwan.

The use of microtechnology and nanotechnology in fabricating vascularized tissues.

PubMed

Obregón, Raquel; Ramón-Azcón, Javier; Ahadian, Samad; Shiku, Hitoshi; Bae, Hojae; Ramalingam, Murugan; Matsue, Tomokazu

2014-01-01

Tissue engineering (TE) is a multidisciplinary research area that combines medicine, biology, and material science. In recent decades, microtechnology and nanotechnology have also been gradually integrated into this field and have become essential components of TE research. Tissues and complex organs in the body depend on a branched blood vessel system. One of the main objectives for TE researchers is to replicate this vessel system and obtain functional vascularized structures within engineered tissues or organs. With the help of new nanotechnology and microtechnology, significant progress has been made. Achievements include the design of nanoscale-level scaffolds with new functionalities, development of integrated and rapid nanotechnology methods for biofabrication of vascular tissues, discovery of new composite materials to direct differentiation of stem and inducible pluripotent stem cells into the vascular phenotype. Although numerous challenges to replicating vascularized tissue for clinical uses remain, the combination of these new advances has yielded new tools for producing functional vascular tissues in the near future.

VESsel GENeration Analysis (VESGEN): Innovative Vascular Mappings for Astronaut Exploration Health Risks and Human Terrestrial Medicine

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia; Kao, David; Valizadegan, Hamed; Martin, Rodney; Murray, Matthew C.; Ramesh, Sneha; Sekaran, Srinivaas

2017-01-01

Currently, astronauts face significant health risks in future long-duration exploration missions such as colonizing the Moon and traveling to Mars. Numerous risks include greatly increased radiation exposures beyond the low earth orbit (LEO) of the ISS, and visual and ocular impairments in response to microgravity environments. The cardiovascular system is a key mediator in human physiological responses to radiation and microgravity. Moreover, blood vessels are necessarily involved in the progression and treatment of vascular-dependent terrestrial diseases such as cancer, coronary vessel disease, wound-healing, reproductive disorders, and diabetes. NASA developed an innovative, globally requested beta-level software, VESsel GENeration Analysis (VESGEN) to map and quantify vascular remodeling for application to astronaut and terrestrial health challenges. VESGEN mappings of branching vascular trees and networks are based on a weighted multi-parametric analysis derived from vascular physiological branching rules. Complex vascular branching patterns are determined by biological signaling mechanisms together with the fluid mechanics of multi-phase laminar blood flow.

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.

Vascular tissue engineering: towards the next generation vascular grafts.

PubMed

Naito, Yuji; Shinoka, Toshiharu; Duncan, Daniel; Hibino, Narutoshi; Solomon, Daniel; Cleary, Muriel; Rathore, Animesh; Fein, Corey; Church, Spencer; Breuer, Christopher

2011-04-30

The application of tissue engineering technology to cardiovascular surgery holds great promise for improving outcomes in patients with cardiovascular diseases. Currently used synthetic vascular grafts have several limitations including thrombogenicity, increased risk of infection, and lack of growth potential. We have completed the first clinical trial evaluating the feasibility of using tissue engineered vascular grafts (TEVG) created by seeding autologous bone marrow-derived mononuclear cells (BM-MNC) onto biodegradable tubular scaffolds. Despite an excellent safety profile, data from the clinical trial suggest that the primary graft related complication of the TEVG is stenosis, affecting approximately 16% of grafts within the first seven years after implantation. Continued investigation into the cellular and molecular mechanisms underlying vascular neotissue formation will improve our basic understanding and provide insights that will enable the rationale design of second generation TEVG. Published by Elsevier B.V.

VEGF signaling inside vascular endothelial cells and beyond.

PubMed

Eichmann, Anne; Simons, Michael

2012-04-01

Vascular endothelial growth factor-A (VEGF-A) has long been recognized as the key regulator of vascular development and function in health and disease. VEGF is a secreted polypeptide that binds to transmembrane tyrosine kinase VEGF receptors on the plasma membrane, inducing their dimerization, activation and assembly of a membrane-proximal signaling complex. Recent studies have revealed that many key events of VEGFR signaling occur inside the endothelial cell and are regulated by endosomal receptor trafficking. Plasma membrane VEGFR interacting molecules, including vascular guidance receptors Neuropilins and Ephrins also regulate VEGFR endocytosis and trafficking. VEGF signaling is increasingly recognized for its roles outside of the vascular system, notably during neural development, and blood vessels regulate epithelial branching morphogenesis. We review here recent advances in our understanding of VEGF signaling and its biological roles. Copyright © 2012 Elsevier Ltd. All rights reserved.

21 CFR 870.3450 - Vascular graft prosthesis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... terephthalate and polytetrafluoroethylene, and it may be coated with a biological coating, such as albumin or... animal origin, including human umbilical cords. (b) Classification. Class II (special controls). The special control for this device is the FDA guidance document entitled “Guidance Document for Vascular...

21 CFR 870.3450 - Vascular graft prosthesis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... terephthalate and polytetrafluoroethylene, and it may be coated with a biological coating, such as albumin or... animal origin, including human umbilical cords. (b) Classification. Class II (special controls). The special control for this device is the FDA guidance document entitled “Guidance Document for Vascular...

21 CFR 870.3450 - Vascular graft prosthesis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... terephthalate and polytetrafluoroethylene, and it may be coated with a biological coating, such as albumin or... animal origin, including human umbilical cords. (b) Classification. Class II (special controls). The special control for this device is the FDA guidance document entitled “Guidance Document for Vascular...

21 CFR 870.3450 - Vascular graft prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... terephthalate and polytetrafluoroethylene, and it may be coated with a biological coating, such as albumin or... animal origin, including human umbilical cords. (b) Classification. Class II (special controls). The special control for this device is the FDA guidance document entitled “Guidance Document for Vascular...

Vascular Cambium Development

PubMed Central

Nieminen, Kaisa; Blomster, Tiina; Helariutta, Ykä; Mähönen, Ari Pekka

2015-01-01

Secondary phloem and xylem tissues are produced through the activity of vascular cambium, the cylindrical secondary meristem which arises among the primary plant tissues. Most dicotyledonous species undergo secondary development, among them Arabidopsis. Despite its small size and herbaceous nature, Arabidopsis displays prominent secondary growth in several organs, including the root, hypocotyl and shoot. Together with the vast genetic resources and molecular research methods available for it, this has made Arabidopsis a versatile and accessible model organism for studying cambial development and wood formation. In this review, we discuss and compare the development and function of the vascular cambium in the Arabidopsis root, hypocotyl, and shoot. We describe the current understanding of the molecular regulation of vascular cambium and compare it to the function of primary meristems. We conclude with a look at the future prospects of cambium research, including opportunities provided by phenotyping and modelling approaches, complemented by studies of natural variation and comparative genetic studies in perennial and woody plant species. PMID:26078728

New therapies for vascular anomalies of the gastrointestinal tract.

PubMed

Fox, Victor L

2018-06-01

Vascular anomalies are a morphologically and biologically diverse group of vascular channel abnormalities that are often congenital but may evolve or change over time in the developing child. Classification is based on a combination of physical and biological properties and clinical behavior that differentiate primarily between tumors and malformations and includes a few provisionally unclassified lesions. Anomalies of the gastrointestinal (GI) tract may present clinically with GI bleeding, abdominal pain, high-output cardiac failure, and malabsorption. This review focuses on new therapies for the treatment of GI bleeding. Important new pharmacological therapies include treatment of hemangioma with non-selective and selective beta-antagonist agents, propranolol and atenolol, and treatment of blue rubber bleb nevus syndrome and cutaneo-visceral angiomatosis with thrombocytopenia (also known as multifocal lymphangioendotheliomatosis with thrombocytopenia) with sirolimus, an inhibitor of the mammalian target of rapamycin. Therapeutic endoscopy may offer an effective alternative to bowel resection for colonic varices and other focal vascular anomalies of the GI tract that fail to respond to pharmacological therapy.

Statistical and data reporting guidelines for the European Journal of Cardio-Thoracic Surgery and the Interactive CardioVascular and Thoracic Surgery.

PubMed

Hickey, Graeme L; Dunning, Joel; Seifert, Burkhardt; Sodeck, Gottfried; Carr, Matthew J; Burger, Hans Ulrich; Beyersdorf, Friedhelm

2015-08-01

As part of the peer review process for the European Journal of Cardio-Thoracic Surgery (EJCTS) and the Interactive CardioVascular and Thoracic Surgery (ICVTS), a statistician reviews any manuscript that includes a statistical analysis. To facilitate authors considering submitting a manuscript and to make it clearer about the expectations of the statistical reviewers, we present up-to-date guidelines for authors on statistical and data reporting specifically in these journals. The number of statistical methods used in the cardiothoracic literature is vast, as are the ways in which data are presented. Therefore, we narrow the scope of these guidelines to cover the most common applications submitted to the EJCTS and ICVTS, focusing in particular on those that the statistical reviewers most frequently comment on. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Bioeffects due to acoustic droplet vaporization

NASA Astrophysics Data System (ADS)

Bull, Joseph

2015-11-01

Encapsulated micro- and nano-droplets can be vaporized via ultrasound, a process termed acoustic droplet vaporization. Our interest is primarily motivated by a developmental gas embolotherapy technique for cancer treatment. In this methodology, infarction of tumors is induced by selectively formed vascular gas bubbles that arise from the acoustic vaporization of vascular microdroplets. Additionally, the microdroplets may be used as vehicles for localized drug delivery, with or without flow occlusion. In this talk, we examine the dynamics of acoustic droplet vaporization through experiments and theoretical/computational fluid mechanics models, and investigate the bioeffects of acoustic droplet vaporization on endothelial cells and in vivo. Early timescale vaporization events, including phase change, are directly visualized using ultra-high speed imaging, and the influence of acoustic parameters on droplet/bubble dynamics is discussed. Acoustic and fluid mechanics parameters affecting the severity of endothelial cell bioeffects are explored. These findings suggest parameter spaces for which bioeffects may be reduced or enhanced, depending on the objective of the therapy. This work was supported by NIH grant R01EB006476.

Vascular pattern of the dentate gyrus is regulated by neural progenitors.

PubMed

Pombero, Ana; Garcia-Lopez, Raquel; Estirado, Alicia; Martinez, Salvador

2018-05-01

Neurogenesis is a vital process that begins during early embryonic development and continues until adulthood, though in the latter case, it is restricted to the subventricular zone and the subgranular zone of the dentate gyrus (DG). In particular, the DG's neurogenic properties are structurally and functionally unique, which may be related to its singular vascular pattern. Neurogenesis and angiogenesis share molecular signals and act synergistically, supporting the concept of a neurogenic niche as a functional unit between neural precursors cells and their environment, in which the blood vessels play an important role. Whereas it is well known that vascular development controls neural proliferation in the embryonary and in the adult brain, by releasing neurotrophic factors; the potential influence of neural cells on vascular components during angiogenesis is largely unknown. We have demonstrated that the reduction of neural progenitors leads to a significant impairment of vascular development. Since VEGF is a potential regulator in the neurogenesis-angiogenesis crosstalk, we were interested in assessing the possible role of this molecule in the hippocampal neurovascular development. Our results showed that VEGF is the molecule involved in the regulation of vascular development by neural progenitor cells in the DG.

Comprehensive mechanical characterization of PLA fabric combined with PCL to form a composite structure vascular graft.

PubMed

Li, Chaojing; Wang, Fujun; Douglas, Graeham; Zhang, Ze; Guidoin, Robert; Wang, Lu

2017-05-01

Vascular grafts made by tissue engineering processes are prone to buckling and twisting, which can impede blood flow and lead to collapse of the vessel. These vascular conduits may suffer not only from insufficient tensile strength, but also from vulnerabilities related to compression, torsion, and pulsatile pressurization. Aiming to develop a tissue engineering-inspired blood conduit, composite vascular graft (cVG) prototypes were created by combining a flexible polylactic acid (PLA) knitted fabric with a soft polycaprolactone (PCL) matrix. The graft is to be populated in-situ with cellular migration and proliferation into the device. Comprehensive characterizations probed the relationship between structure and mechanical properties of the different cVG prototypes. The composite grafts exhibited major improvements in mechanical characteristics compared to single-material devices, with particular improvement in compression and torsional resistance. A commercial expanded polytetrafluoroethylene (ePTFE) vascular graft was used as a control against the proposed composite vascular grafts. CVG devices showed high tensile strength, high bursting strength, and improved suture retention. Compression, elastic recovery, and compliance were similar to those for the ePTFE graft. Copyright © 2016 Elsevier Ltd. All rights reserved.

A new method for in vivo visualization of vessel remodeling using a near-infrared dye

PubMed Central

Billaud, Marie; Ross, Jeremy A; Greyson, Mark A; Bruce, Anthony C; Seaman, Scott A; Heberlein, Katherine R; Han, Jenny; Best, Angela K; Peirce, Shayn M; Isakson, Brant E

2011-01-01

Intro Vascular obstructive events can be partially compensated for by remodeling processes that increase vessel diameter and collateral tortuosity. However, methods for visualizing remodeling events in vivo and with temporal comparisons from the same animal remain elusive. Methods Using a novel infrared conjugated polyethylene glycol dye, we investigated the possibility of intravital vascular imaging of the mouse ear before and after ligation of the primary feeder artery. For comparison, we used two different mouse models known to have impaired vascular remodeling post ligation (i.e. aged and PAI-1−/− mice). The results obtained with the infrared dye were confirmed using immunofluorescence labeling of the ear microvasculature with confocal microscopy. Results After ligation, increases in vessel diameter (between 10% and 60%) and tortuosity (approximately 15%) were observed in C57Bl/6 mice using both the infrared dye and the immunofluorescence technique. However, aged C57Bl/6 and PAI-1−/− mice did not show vascular remodeling following ligation. Conclusion Vascular remodeling can be visualized and accurately quantified using a new infrared dye in vivo. This analysis technique could be generally employed for quantitative investigations of changes in vascular remodeling. PMID:21418375

Can microRNAs control vascular smooth muscle phenotypic modulation and the response to injury?

PubMed Central

Albinsson, Sebastian

2011-01-01

Vascular smooth muscle cell (VSMC) migration and proliferation are critical events in vascular proliferative diseases. Recent studies have established microRNAs (miRNAs) as important mediators for the modulation of VSMC phenotype by targeting transcription factors and the cytoskeleton, which act as molecular switches for VSMC differentiation. The importance of miRNAs for VSMC development, differentiation, and function is evident by the fact that loss of the miRNA processing enzyme Dicer in VSMCs results in embryonic lethality due to severe vascular abnormalities. Similar abnormalities are observed in adult miR-143/145 knockout mice, indicating that these miRNAs are important for VSMC differentiation and function. However, since miR-143/145 knockout is not embryonically lethal, additional miRNA must be required during embryonic development of VSMCs. In addition, specific miRNAs such as miR-145, miR-21, and miR-221 have been found to regulate neointimal hyperplasia following vascular injury, which provides interesting possibilities for future therapeutical targets against vascular disease. Herein, we summarize recent advances regarding the role of miRNAs in VSMC phenotype modulation and response to injury. PMID:20841497

Potential Approaches to Enhance the Effects of Estrogen on Senescent Blood Vessels and Postmenopausal Cardiovascular Disease

PubMed Central

Khalil, Raouf A.

2010-01-01

Cardiovascular disease (CVD) is more common in postmenopausal than premenopausal women, suggesting vascular protective effects of estrogen. Vascular estrogen receptors ERα, ERβ and a transmembrane estrogen-binding protein GPR30 have been described. Also, experimental studies have demonstrated vasodilator effects of estrogen on the endothelium, vascular smooth muscle and extracellular matrix. However, randomized clinical trials have not supported vascular benefits of menopausal hormone therapy (MHT), possibly due to the subjects' advanced age and age-related changes in estrogen synthesis and metabolic pathways, the vascular ERs number, distribution and integrity, and the post-ER vascular signaling pathways. Current MHT includes natural estrogens such as conjugated equine estrogen, as well as synthetic and semi-synthetic estrogens. New estrogenic formulations and hormone combinations have been developed. Phytoestrogens is being promoted as an alternative MHT. Specific ER modulators (SERMs), and selective agonists for ERα such as PPT, ERβ such as DPN, and GPR30 such as G1 are being evaluated. In order to enhance the vascular effectiveness of MHT, its type, dose, route of administration and timing may need to be customized depending on the subject's age and pre-existing CVD. Also, the potential interaction of estrogen with progesterone and testosterone on vascular function may need to be considered in order to maximize the vascular benefits of MHT on senescent blood vessels and postmenopausal CVD. PMID:20210774

A novel image processing workflow for the in vivo quantification of skin microvasculature using dynamic optical coherence tomography.

PubMed

Zugaj, D; Chenet, A; Petit, L; Vaglio, J; Pascual, T; Piketty, C; Bourdes, V

2018-02-04

Currently, imaging technologies that can accurately assess or provide surrogate markers of the human cutaneous microvessel network are limited. Dynamic optical coherence tomography (D-OCT) allows the detection of blood flow in vivo and visualization of the skin microvasculature. However, image processing is necessary to correct images, filter artifacts, and exclude irrelevant signals. The objective of this study was to develop a novel image processing workflow to enhance the technical capabilities of D-OCT. Single-center, vehicle-controlled study including healthy volunteers aged 18-50 years. A capsaicin solution was applied topically on the subject's forearm to induce local inflammation. Measurements of capsaicin-induced increase in dermal blood flow, within the region of interest, were performed by laser Doppler imaging (LDI) (reference method) and D-OCT. Sixteen subjects were enrolled. A good correlation was shown between D-OCT and LDI, using the image processing workflow. Therefore, D-OCT offers an easy-to-use alternative to LDI, with good repeatability, new robust morphological features (dermal-epidermal junction localization), and quantification of the distribution of vessel size and changes in this distribution induced by capsaicin. The visualization of the vessel network was improved through bloc filtering and artifact removal. Moreover, the assessment of vessel size distribution allows a fine analysis of the vascular patterns. The newly developed image processing workflow enhances the technical capabilities of D-OCT for the accurate detection and characterization of microcirculation in the skin. A direct clinical application of this image processing workflow is the quantification of the effect of topical treatment on skin vascularization. © 2018 The Authors. Skin Research and Technology Published by John Wiley & Sons Ltd.

The Epidemiology of Vascular Injury in the Wars in Iraq and Afghanistan

DTIC Science & Technology

2011-06-01

scale (AIS) and In- ternational Classification of Diseases , Ninth Revision (ICD-9) codes for vascular injury (arterial and venous) and vascular injury...denominator of significant wounding in the tabulation of rates. Nonbattle-related injuries (ie, disease nonbattle or DNBI) were not included in the...Coronary 2 0.13 Celiac 3 0.19 Superior mesenteric artery 13 0.83 Aorta 45 2.9 Vena cava (n = 21) Superior 5 0.32 Inferior 16 1.1 Iliac (n = 61) Iliac

[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.

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.

Using biplanar fluoroscopy to guide radiopaque vascular injections: a new method for vascular imaging.

PubMed

O'Brien, Haley D; Williams, Susan H

2014-01-01

Studying vascular anatomy, especially in the context of relationships with hard tissues, is of great interest to biologists. Vascular studies have provided significant insight into physiology, function, phylogenetic relationships, and evolutionary patterns. Injection of resin or latex into the vascular system has been a standard technique for decades. There has been a recent surge in popularity of more modern methods, especially radiopaque latex vascular injection followed by CT scanning and digital "dissection." This technique best displays both blood vessels and bone, and allows injections to be performed on cadaveric specimens. Vascular injection is risky, however, because it is not a standardizable technique, as each specimen is variable with regard to injection pressure and timing. Moreover, it is not possible to view the perfusion of injection medium throughout the vascular system of interest. Both data and rare specimens can therefore be lost due to poor or excessive perfusion. Here, we use biplanar video fluoroscopy as a technique to guide craniovascular radiopaque latex injection. Cadaveric domestic pigs (Sus scrofa domestica) and white-tailed deer (Odocoileus virginianus) were injected with radiopaque latex under guidance of fluoroscopy. This method was found to enable adjustments, in real-time, to the rate, location, and pressure at which latex is injected in order to avoid data and specimen loss. In addition to visualizing the injection process, this technique can be used to determine flow patterns, and has facilitated the development of consistent markers for complete perfusion.

Noncardiac Vascular Toxicities of Vascular Endothelial Growth Factor Inhibitors in Advanced Cancer: A Review

PubMed Central

Bowen, Joanne; Gibson, Rachel; Tan, Thean; Okera, Meena; Stringer, Andrea

2011-01-01

Summary. The introduction of molecularly targeted anticancer therapies has brought the promise of longer survival times for select patients with cancers previously considered untreatable. However, it has also brought new toxicities that require understanding and management, sometimes for long periods of time. Vascular endothelial growth factor inhibitors are associated with a broad range of adverse effects, with vascular toxicity being particularly serious. This review focuses on the current understanding of the pathophysiology and mechanisms of macrovascular toxicities (hypertension, hemorrhage, and thromboembolism), their incidence and severity, the current clinical management, and implications in the advanced cancer setting. Movement of these agents into the early disease setting will alter the impact of these toxicities. Search Strategy and Selection Criteria. Information for this review was collected by searching PubMed/Medline and American Society of Clinical Oncology abstract databases. The medical subject heading terms used included toxicity, hypertension, thromboembolism, hemorrhage, intestinal perforation, risk factors, pharmacokinetics, and metabolism, combined with free text search terms including, but not limited to, VEGF inhibitor*, bevacizumab, sunitinib, and sorafenib. Articles published in English before March 2010 were included, in addition to information from case reports and pharmaceutical agent package inserts. PMID:21441297

Integrated Fellowship in Vascular Surgery and Intervention Radiology

PubMed Central

Messina, Louis M.; Schneider, Darren B.; Chuter, Timothy A. M.; Reilly, Linda M.; Kerlan, Robert K.; LaBerge, Jeane M.; Wilson, Mark W.; Ring, Ernest J.; Gordon, Roy L.

2002-01-01

Objective To evaluate an integrated fellowship in vascular surgery and interventional radiology initiated to train vascular surgeons in endovascular techniques and to train radiology fellows in clinical aspects of vascular diseases. Summary Background Data The rapid evolution of endovascular techniques for the treatment of vascular diseases requires that vascular surgeons develop proficiency in these techniques and that interventional radiologists develop proficiency in the clinical evaluation and management of patients who are best treated with endovascular techniques. In response to this need the authors initiated an integrated fellowship in vascular surgery and interventional radiology and now report their interim results. Methods Since 1999 vascular fellows and radiology fellows performed an identical year-long fellowship in interventional radiology. During the fellowship, vascular surgery and radiology fellows perform both vascular and nonvascular interventional procedures. Both vascular surgery and radiology-based fellows spend one quarter of the year on the vascular service performing endovascular aortic aneurysm repairs and acquiring clinical experience in the vascular surgery inpatient and outpatient services. Vascular surgery fellows then complete an additional year-long fellowship in vascular surgery. To evaluate the type and number of interventional radiology procedures, the authors analyzed records of cases performed by all interventional radiology and vascular surgery fellows from a prospectively maintained database. The attitudes of vascular surgery and interventional radiology faculty and fellows toward the integrated fellowship were surveyed using a formal questionnaire. Results During the fellowship each fellow performed an average of 1,201 procedures, including 808 vascular procedures (236 diagnostic angiograms, 70 arterial interventions, 59 diagnostic venograms, 475 venous interventions, and 43 hemodialysis graft interventions) and 393 nonvascular procedures. On average fellows performed 20 endovascular aortic aneurysm repairs per year. There was no significant difference between the vascular surgery and radiology fellows in either the spectrum or number of cases performed. Eighty-eight percent (23/26) of the questionnaires were completed and returned. Both interventional radiologists and vascular surgeons strongly supported the integrated fellowship model and favored continuation of the integrated program. Vascular surgery and interventional radiology faculty members wanted additional training in clinical vascular surgery for the radiology-based fellows. With the exception of the radiology fellows there was uniform agreement that vascular surgery fellows benefit from training in nonvascular aspects of interventional radiology. Conclusions Integration of vascular surgery and interventional radiology fellowships is feasible and is mutually beneficial to both disciplines. Furthermore, the integrated fellowship provides exceptional training for vascular surgery and interventional radiology fellows in all catheter-based techniques that far exceeds the minimum requirements for credentialing suggested by various professional societies. There is a clear need for cooperation and active involvement on the parts of the American Board of Radiology and the American Board of Surgery and its Vascular Board to create hybrid training programs that meet mutually agreed-on criteria that document sufficient acquisition of both the cognitive and technical skills required to manage patients undergoing endovascular procedures safely and effectively. PMID:12368668

Bioprinting for vascular and vascularized tissue biofabrication.

PubMed

Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

2017-03-15

Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision, which holds a great promise in fabrication of vascular or vascularized tissues for transplantation use. Although a great progress has recently been made on building perfusable tissues and branched vascular network, a comprehensive review on the state-of-the-art in vascular and vascularized tissue bioprinting has not reported so far. This contribution is thus significant because it discusses the use of three major bioprinting modalities in vascular tissue biofabrication for the first time in the literature and compares their strengths and limitations in details. Moreover, the use of scaffold-based and scaffold-free bioprinting is expounded within the domain of vascular tissue fabrication. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Emerging role of thalidomide in the treatment of gastrointestinal bleeding.

PubMed

McFarlane, Michael; O'Flynn, Lauren; Ventre, Rachel; Disney, Benjamin R

2018-04-01

Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.

Endovascular Management of Extra-cranial Supra-aortic Vascular Injuries

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

Almazedi, Bahir, E-mail: b.almazedi@doctors.org.uk; Lyall, Harpreet; Bhatnagar, Priya

Supra-aortic vessel injuries are uncommon but can be life-threatening and surgically challenging. Trauma to these vessels may be blunt or penetrating, including iatrogenic trauma following the insertion of central venous lines, which may be preventable. Recent advances in technology have resulted in endovascular therapy becoming a common first-line treatment, and interventional radiologists now play a major role in the management of these vascular injuries. We review the literature on the endovascular management of these types of injuries and describe a spectrum of case-based extra-cranial supra-aortic vascular injuries managed at our institution and the range of imaging appearances, including active contrast extravasation,more » traumatic vessel occlusion, true aneurysms, pseudoaneurysms, and arteriovenous fistulae.« less

GPER inhibits diabetes-mediated RhoA activation to prevent vascular endothelial dysfunction.

PubMed

Li, Zilin; Cheng, Liang; Liang, Hongliang; Duan, Weixun; Hu, Jing; Zhi, Weiwei; Yang, Jinbao; Liu, Zhenhua; Zhao, Minggao; Liu, Jincheng

2016-02-01

The effect of estrogen receptors on diabetes-induced vascular dysfunction is critical, but ambiguous. Individuals with diabetic vascular disease may require estrogen receptor-specific targeted therapy in the future. The G protein-coupled estrogen receptor (GPER) has beneficial effects on vascular function. However, its fundamental mechanisms are unclear. The RhoA/Rho-kinase pathway contributes to diabetic vascular complications, whereas estrogen can suppress Rho-kinase function. Thus, we assumed that GPER inhibits diabetes-mediated RhoA activation to prevent vascular dysfunction. We further investigated the underlying mechanisms involved in this process. Vascular endothelial cells and ex vivo cultured ovariectomized (OVX) C57BL/6 mouse aortae were treated with high glucose (HG) alone or in combination with GPER agonist (G1). G1 treatment was also administered to OVX db/db mice for 8 weeks. An ex-vivo isovolumic myograph was used to analyze the endothelium-dependent vasodilation and endothelium-independent contraction of mouse aortae. Apoptosis, oxidative stress, and inflammation were attenuated in G1-pretreated vascular endothelial cells. G1 significantly decreased the phosphorylation of inhibitory endothelial nitric oxide (NO) synthase residue threonine 495 (eNOS Thr495), inhibited RhoA expression, and increased NO production. Additionally, G1 rescued the impaired endothelium-dependent relaxation and inhibited RhoA activation in the thoracic aorta of OVX db/db mice and ex-vivo cultured OVX C57BL/6 mouse aortae treated with HG. Estrogens acting via GPER could protect vascular endothelium, and GPER activation might elicit ERα-independent effect to inhibit RhoA/Rho-kinase pathway. Additionally, GPER activation might reduce vascular smooth muscle contraction by inhibiting RhoA activation. Thus, the results of the present study suggest a new therapeutic paradigm for end-stage vascular dysfunction by inhibiting RhoA/Rho-kinase pathway via GPER activation. Copyright © 2016 Elsevier GmbH. All rights reserved.

[Self-consciousness in elderly persons with cognitive impairment and vascular dementia].

PubMed

Dubinina, E A; Novikova, Yu G; Kalitskaya, A V; Finagentova, N V

2016-01-01

Self-consciousness was compared in 17 elderly (aged 65-89 years old) persons with cognitive impairment without dementia and 17 patients with vascular dementia. Neurocognitive functions and mental health complaints were evaluated. Neuropsychological assessment included evaluation of higher psychological functions, such as attention, memory, conceptualization, gnosis (optic, acoustic), manual skill, speech. Older persons with cognitive impairment assessed their neurocognitive functions adequately. Patients with vascular dementia usually denied cognitive deficit or explained it as a result of aging. Regardless of physical health, older persons with cognitive impairment have active attitude to aging. They could find ways of compensation of cognitive deficits without assistance. Patients with vascular dementia could not compensate their cognitive deficit even with support.

Retinitis Pigmentosa Associated with Vasoproliferative Tumors and Coats-like Fundus

PubMed Central

Ghassemi, Fariba; Akbari-Kamrani, Marjan

2013-01-01

Purpose To report two cases of retinitis pigmentosa (RP) associated with vasoproliferative tumors (VPTs) and Coats-like fundus. Case Reports Two patients with RP presented with recent loss of vision due to combined VPTs and Coats-like retinal vascular alterations. One patient had two VPTs with adjacent capillary nonperfusion, telangiectasia and aneurysmal vascular changes in one eye. The other patient had prominent VPT with Coats-like retinal vascular alterations in both eyes. These lesions received treatment resulting in improved vision in both patients. Conclusion Although rare, VPTs and Coats-like retinal vascular alterations including retinal exudation associated with telangiectatic vessels, aneurysmal changes and capillary nonperfusion may occur in patients with RP. PMID:24349671

Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in Angiogenesis: Isoform-Specific Effects

PubMed Central

Wang, Haibo; Hartnett, M. Elizabeth

2017-01-01

Angiogenesis is the formation of new blood vessels from preexisting ones and is implicated in physiologic vascular development, pathologic blood vessel growth, and vascular restoration. This is in contrast to vasculogenesis, which is de novo growth of vessels from vascular precursors, or from vascular repair that occurs when circulating endothelial progenitor cells home into an area and develop into blood vessels. The objective of this review is to discuss the isoform-specific role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in physiologic and pathologic angiogenesis and vascular repair, but will not specifically address vasculogenesis. As the major source of reactive oxygen species (ROS) in vascular endothelial cells (ECs), NOX has gained increasing attention in angiogenesis. Activation of NOX leads to events necessary for physiologic and pathologic angiogenesis, including EC migration, proliferation and tube formation. However, activation of different NOX isoforms has different effects in angiogenesis. Activation of NOX2 promotes pathologic angiogenesis and vascular inflammation, but may be beneficial in revascularization in the hindlimb ischemic model. In contrast, activation of NOX4 appears to promote physiologic angiogenesis mainly by protecting the vasculature during ischemia, hypoxia and inflammation and by restoring vascularization, except in models of oxygen-induced retinopathy and diabetes where NOX4 activation leads to pathologic angiogenesis. PMID:28587189

Bioengineered vascular constructs as living models for in vitro cardiovascular research.

PubMed

Wolf, Frederic; Vogt, Felix; Schmitz-Rode, Thomas; Jockenhoevel, Stefan; Mela, Petra

2016-09-01

Cardiovascular diseases represent the most common cause of morbidity and mortality worldwide. In this review, we explore the potential of bioengineered vascular constructs as living models for in vitro cardiovascular research to advance the current knowledge of pathophysiological processes and support the development of clinical therapies. Bioengineered vascular constructs capable of recapitulating the cellular and mechanical environment of native vessels represent a valuable platform to study cellular interactions and signaling cascades, test drugs and medical devices under (patho)physiological conditions, with the additional potential benefit of reducing the number of animals required for preclinical testing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

PubMed Central

Montezano, Augusto C.

2014-01-01

Abstract Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redox-sensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20, 164–182. PMID:23600794

Time-resolved 3D MR velocity mapping at 3T: improved navigator-gated assessment of vascular anatomy and blood flow.

PubMed

Markl, Michael; Harloff, Andreas; Bley, Thorsten A; Zaitsev, Maxim; Jung, Bernd; Weigang, Ernst; Langer, Mathias; Hennig, Jürgen; Frydrychowicz, Alex

2007-04-01

To evaluate an improved image acquisition and data-processing strategy for assessing aortic vascular geometry and 3D blood flow at 3T. In a study with five normal volunteers and seven patients with known aortic pathology, prospectively ECG-gated cine three-dimensional (3D) MR velocity mapping with improved navigator gating, real-time adaptive k-space ordering and dynamic adjustment of the navigator acceptance criteria was performed. In addition to morphological information and three-directional blood flow velocities, phase-contrast (PC)-MRA images were derived from the same data set, which permitted 3D isosurface rendering of vascular boundaries in combination with visualization of blood-flow patterns. Analysis of navigator performance and image quality revealed improved scan efficiencies of 63.6%+/-10.5% and temporal resolution (<50 msec) compared to previous implementations. Semiquantitative evaluation of image quality by three independent observers demonstrated excellent general image appearance with moderate blurring and minor ghosting artifacts. Results from volunteer and patient examinations illustrate the potential of the improved image acquisition and data-processing strategy for identifying normal and pathological blood-flow characteristics. Navigator-gated time-resolved 3D MR velocity mapping at 3T in combination with advanced data processing is a powerful tool for performing detailed assessments of global and local blood-flow characteristics in the aorta to describe or exclude vascular alterations. Copyright (c) 2007 Wiley-Liss, Inc.

Monocyte Chemoattractant Protein-1 in the choroid plexus: a potential link between vascular pro-inflammatory mediators and the CNS during peripheral tissue inflammation

PubMed Central

Mitchell, K.; Yang, H.-Y. T.; Berk, J. D.; Tran, J. H.; Iadarola, M. J.

2009-01-01

During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of CSF production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the SCYA2 gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared to other CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the NF-κβ signaling cascade including TNF-α, IL-1β and IκBα in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding E-selectin, a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during peripheral tissue inflammation, likely initiated by blood-borne inflammatory mediators, which may modify events in CNS. PMID:19032979

Standard operating procedures for vascular surgery in erectile dysfunction: revascularization and venous procedures.

PubMed

Sohn, Michael; Hatzinger, Martin; Goldstein, Irwin; Krishnamurti, Sudhakar

2013-01-01

The impact of penile blood supply on erectile function was recognized some 500 years ago. At the turn of the 20th century first results of penile venous ligation were published and in 1973 the first surgical attempts to restore penile arterial inflow were undertaken. Numerous techniques were published in the meantime, but inclusion criteria, patient selection, and success evaluation differed extremely between study groups. To develop evidence-based standard operating procedures (SOPs) for vascular surgery in erectile dysfunction, based on recent state of the art consensus reports and recently published articles in peer-reviewed journals. Based on the recent publication of the consensus process during the 2009 International Consultation on Sexual Medicine in Paris, recommendations are derived for diagnosis and surgical treatment of vascular erectile dysfunction. In addition several recent publications in this field not mentioned in the consensus statements are included in the discussion. The Oxford system of evidence-based review was systematically applied. Due to the generally low level of evidence in this field expert opinions were accepted, if published after a well-defined consensus process in peer-reviewed journals. Referring to penile revascularization it may be concluded, that in the face of missing randomized trials, only recommendations grade D may be given: this kind of surgery may be offered to men less than 55 years, who are nonsmokers, nondiabetic, and demonstrate isolated arterial stenoses in the absence of generalized vascular disease. The evidence level for recommendations concerning penile venous ligations may be even lower. Too many unsolved controversies exist and universal diagnostic criteria for patient selection as well as operative technique selection have not been unequivocally established. This kind of surgery is still considered investigational but may be offered in special situations on an individualized basis in an investigational or research setting after obtaining written consent, using both pre- and postoperatively validated measuring instruments of success evaluation. SOPs for penile revascularization procedures can be developed, concerning a highly selected patient group with isolated arterial stenoses. Based on the available data it is not yet possible to define SOPs for surgical treatment of corporal veno-occlusive dysfunction. © 2012 International Society for Sexual Medicine.

Fabrication, vascularization and osteogenic properties of a novel synthetic biomimetic induced membrane for the treatment of large bone defects

PubMed Central

Browne, Christopher; Bishop, Julius; Yang, Yunzhi

2014-01-01

The induced membrane has been widely used in the treatment of large bone defects but continues to be limited by a relatively lengthy healing process and a requisite two stage surgical procedure. Here we report the development and characterization of a synthetic biomimetic induced membrane (BIM) consisting of an inner highly pre-vascularized cell sheet and an outer osteogenic layer using cell sheet engineering. The pre-vascularized inner layer was formed by seeding human umbilical vein endothelial cells (HUVECs) on a cell sheet comprised of a layer of undifferentiated human bone marrow-derived mesenchymal stem cells (hMSCs). The outer osteogenic layer was formed by inducing osteogenic differentiation of hMSCs. In vitro results indicated the undifferentiated hMSCs cell sheet facilitated the alignment of HUVECs and significantly promoted the formation of vascular-like networks. Furthermore, seeded HUVECs rearranged the extracellular matrix produced by hMSCs sheet. After subcutaneously implantation, the composite constructs showed rapid vascularization and anastomosis with the host vascular system, forming functional blood vessels in vivo. Osteogenic potential of the BIM was evidenced by immunohistochemistry staining of osteocalcin, tartrate-resistant acid phosphatase (TRAP) staining, and alizarin red staining. In summary, the synthetic BIM showed rapid vascularization, significant anastomoses, and osteogenic potential in vivo. This synthetic BIM has the potential for treatment of large bone defects in the absence of infection. PMID:24747351

Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia

PubMed Central

Francardo, Veronica; Lindgren, Hanna S.; Sillivan, Stephanie E.; O’Sullivan, Sean S.; Luksik, Andrew S.; Vassoler, Fair M.; Lees, Andrew J.; Konradi, Christine

2011-01-01

Angiogenesis and increased permeability of the blood–brain barrier have been reported to occur in animal models of Parkinson’s disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood–brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson’s disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson’s disease. PMID:21771855

Digital image processing of vascular angiograms

NASA Technical Reports Server (NTRS)

Selzer, R. H.; Beckenbach, E. S.; Blankenhorn, D. H.; Crawford, D. W.; Brooks, S. H.

1975-01-01

The paper discusses the estimation of the degree of atherosclerosis in the human femoral artery through the use of a digital image processing system for vascular angiograms. The film digitizer uses an electronic image dissector camera to scan the angiogram and convert the recorded optical density information into a numerical format. Another processing step involves locating the vessel edges from the digital image. The computer has been programmed to estimate vessel abnormality through a series of measurements, some derived primarily from the vessel edge information and others from optical density variations within the lumen shadow. These measurements are combined into an atherosclerosis index, which is found in a post-mortem study to correlate well with both visual and chemical estimates of atherosclerotic disease.

Triamcinolone Acetonide Selectively Inhibits Angiogenesis in Small Blood Vessels and Decreases Vessel Diameter within the Vascular Tree

NASA Technical Reports Server (NTRS)

McKay, Terri L.; Gredeon, Dan J.; Vickerman, Mary B.; Hylton, alan G.; Ribita, Daniela; Olar, Harry H.; Kaiser, Peter K.; Parsons-Wingerter, Patricia

2007-01-01

The steroid triamcinolone acetonide (TA) is a potent anti-angiogenesis drug used to treat retinal vascular diseases that include diabetic retinopathy, vascular occlusions and choroidal neovascularization. To quantify the effects of TA on branching morphology within the angiogenic microvascular tree of the chorioallantoic membrane (CAM) of quail embryos. Increasing concentrations of TA (0-16 ng/ml) were applied topically on embryonic day 7 (E7) to the chorioallantoic membrane (CAM) of quail embryos cultured in Petri dishes, and incubated for an additional 24 or 48 hours until fixation. Binary (black/white) microscopic images of arterial end points were quantified by VESGEN software (for Generational Analysis of Vessel Branching) to obtain major vascular parameters that include vessel diameter (Dv), fractal dimension (Df), tortuosity (Tv) and densities of vessel area, length, number and branch point (Av, Lv, Nv and Brv). For assessment of specific changes in vascular morphology induced by TA, the VESGEN software automatically segmented the vascular tree into branching generations (G1...G10) according to changes in vessel diameter and branching. Vessel density decreased significantly up to 34% as the function of increasing concentration of TA according to Av, Lv, Brv, Nv and Df. TA selectively inhibited the growth of new, small vessels, because Lv decreased from 13.14plus or minus 0.61 cm/cm2 for controls to 8.012 plus or minus 0.82 cm/cm2 at 16 ng TA/ml in smaller branching generations (G7-G10), and for Nv from 473.83 plus or minus 29.85 cm(-)2 to 302.32 plus or minus 33.09 cm-()2. In contrast, vessel diameter (Dv) decreased throughout the vascular tree (G1-G10).

Value of a skin island flap as a postoperative predictor of vascularized fibula graft viability in extensive diaphyseal bone defect reconstruction.

PubMed

Guo, Q-F; Xu, Z-H; Wen, S-F; Liu, Q-H; Liu, S-H; Wang, J-W; Li, X-Y; Xu, H-H

2012-09-01

To evaluate the feasibility and reliability of free vascularized fibular graft with skin island flap for reconstruction of large diaphyseal bone defect. The clinical results of vascularized fibular graft and experiences related to the importance and reliability of a monitoring island flap for the reconstruction of various long-bone defects were reviewed in 87 patients. Bony reconstruction was achieved in 82 of the 87 patients. Arterial thrombosis of anastomosed vessel in two patients and venous congestion of monitoring flap in nine patients occurred in the early postoperative periods. All of them were managed by immediate thrombectomy and reanastomosis, alternatively the thrombotic veins were replaced by new veins to anastomose with the superficial veins in five patients. Partial flap necrosis was noted in six patients, but additional surgical intervention was not required. The vascularized fibula survived and bony fusion was achieved in all patients. Postoperative stress fractures of the fibula graft occurred in 19 (21.8%) patients (once in seven patients, twice in five patients, three or more times in seven) as the mechanical stress to the graft increased. Included fracture on the tibia in 12 patients, humerus in one and femur in six. Treatments included casting in 11 patients, percutaneous pinning in one case, and adjustment of external fixator in seven patients. Bony union was finally achieved an average of 9.6 months after fracture. Correct alignment between the recipient bone and the external fixator is a prerequisite to preventing graft fracture. Vascularized fibula transfer is a valuable procedure for long-bone defects, and a skin island-monitoring flap is a simple, extremely useful, and reliable method for assessing the vascular status of vascularized fibula. Level IV. Retrospective study. Copyright © 2012. Published by Elsevier Masson SAS.

Optimal combination treatment and vascular outcomes in recent ischemic stroke patients by premorbid risk level.

PubMed

Park, Jong-Ho; Ovbiagele, Bruce

2015-08-15

Optimal combination of secondary stroke prevention treatment including antihypertensives, antithrombotic agents, and lipid modifiers is associated with reduced recurrent vascular risk including stroke. It is unclear whether optimal combination treatment has a differential impact on stroke patients based on level of vascular risk. We analyzed a clinical trial dataset comprising 3680 recent non-cardioembolic stroke patients aged ≥35 years and followed for 2 years. Patients were categorized by appropriateness levels 0 to III depending on the number of the drugs prescribed divided by the number of drugs potentially indicated for each patient (0=none of the indicated medications prescribed and III=all indicated medications prescribed [optimal combination treatment]). High-risk was defined as having a history of stroke or coronary heart disease (CHD) prior to the index stroke event. Independent associations of medication appropriateness level with a major vascular event (stroke, CHD, or vascular death), ischemic stroke, and all-cause death were analyzed. Compared with level 0, for major vascular events, the HR of level III in the low-risk group was 0.51 (95% CI: 0.20-1.28) and 0.32 (0.14-0.70) in the high-risk group; for stroke, the HR of level III in the low-risk group was 0.54 (0.16-1.77) and 0.25 (0.08-0.85) in the high-risk group; and for all-cause death, the HR of level III in the low-risk group was 0.66 (0.09-5.00) and 0.22 (0.06-0.78) in the high-risk group. Optimal combination treatment is related to a significantly lower risk of future vascular events and death among high-risk patients after a recent non-cardioembolic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Vascular and Inflammatory Factors in the Pathophysiology of Blast-Induced Brain Injury

PubMed Central

Elder, Gregory A.; Gama Sosa, Miguel A.; De Gasperi, Rita; Stone, James Radford; Dickstein, Dara L.; Haghighi, Fatemeh; Hof, Patrick R.; Ahlers, Stephen T.

2015-01-01

Blast-related traumatic brain injury (TBI) has received much recent attention because of its frequency in the conflicts in Iraq and Afghanistan. This renewed interest has led to a rapid expansion of clinical and animal studies related to blast. In humans, high-level blast exposure is associated with a prominent hemorrhagic component. In animal models, blast exerts a variety of effects on the nervous system including vascular and inflammatory effects that can be seen with even low-level blast exposures which produce minimal or no neuronal pathology. Acutely, blast exposure in animals causes prominent vasospasm and decreased cerebral blood flow along with blood-brain barrier breakdown and increased vascular permeability. Besides direct effects on the central nervous system, evidence supports a role for a thoracically mediated effect of blast; whereby, pressure waves transmitted through the systemic circulation damage the brain. Chronically, a vascular pathology has been observed that is associated with alterations of the vascular extracellular matrix. Sustained microglial and astroglial reactions occur after blast exposure. Markers of a central and peripheral inflammatory response are found for sustained periods after blast injury and include elevation of inflammatory cytokines and other inflammatory mediators. At low levels of blast exposure, a microvascular pathology has been observed in the presence of an otherwise normal brain parenchyma, suggesting that the vasculature may be selectively vulnerable to blast injury. Chronic immune activation in brain following vascular injury may lead to neurobehavioral changes in the absence of direct neuronal pathology. Strategies aimed at preventing or reversing vascular damage or modulating the immune response may improve the chronic neuropsychiatric symptoms associated with blast-related TBI. PMID:25852632

Improving Global Vascular Risk Prediction with Behavioral and Anthropometric Factors: The Multi-ethnic Northern Manhattan Cohort Study

PubMed Central

Sacco, Ralph L.; Khatri, Minesh; Rundek, Tatjana; Xu, Qiang; Gardener, Hannah; Boden-Albala, Bernadette; Di Tullio, Marco R.; Homma, Shunichi; Elkind, Mitchell SV; Paik, Myunghee C

2010-01-01

Objective To improve global vascular risk prediction with behavioral and anthropometric factors. Background Few cardiovascular risk models are designed to predict the global vascular risk of MI, stroke, or vascular death in multi-ethnic individuals, and existing schemes do not fully include behavioral risk factors. Methods A randomly-derived, population-based, prospective cohort of 2737 community participants free of stroke and coronary artery disease were followed annually for a median of 9.0 years in the Northern Manhattan Study (mean age 69 years; 63.2% women; 52.7% Hispanic, 24.9% African-American, 19.9% white). A global vascular risk score (GVRS) predictive of stroke, myocardial infarction, or vascular death was developed by adding variables to the traditional Framingham cardiovascular variables based on the likelihood ratio criterion. Model utility was assessed through receiver operating characteristics, calibration, and effect on reclassification of subjects. Results Variables which significantly added to the traditional Framingham profile included waist circumference, alcohol consumption, and physical activity. Continuous measures for blood pressure and fasting blood sugar were used instead of hypertension and diabetes. Ten -year event-free probabilities were 0.95 for the first quartile of GVRS, 0.89 for the second quartile, 0.79 for the third quartile, and 0.56 for the fourth quartile. The addition of behavioral factors in our model improved prediction of 10 -year event rates compared to a model restricted to the traditional variables. Conclusion A global vascular risk score that combines both traditional, behavioral, and anthropometric risk factors, uses continuous variables for physiological parameters, and is applicable to non-white subjects could improve primary prevention strategies. PMID:19958966

Algorithm-Based Motion Magnification for Video Processing in Urological Laparoscopy.

PubMed

Adams, Fabian; Schoelly, Reto; Schlager, Daniel; Schoenthaler, Martin; Schoeb, Dominik S; Wilhelm, Konrad; Hein, Simon; Wetterauer, Ulrich; Miernik, Arkadiusz

2017-06-01

Minimally invasive surgery is in constant further development and has replaced many conventional operative procedures. If vascular structure movement could be detected during these procedures, it could reduce the risk of vascular injury and conversion to open surgery. The recently proposed motion-amplifying algorithm, Eulerian Video Magnification (EVM), has been shown to substantially enhance minimal object changes in digitally recorded video that is barely perceptible to the human eye. We adapted and examined this technology for use in urological laparoscopy. Video sequences of routine urological laparoscopic interventions were recorded and further processed using spatial decomposition and filtering algorithms. The freely available EVM algorithm was investigated for its usability in real-time processing. In addition, a new image processing technology, the CRS iimotion Motion Magnification (CRSMM) algorithm, was specifically adjusted for endoscopic requirements, applied, and validated by our working group. Using EVM, no significant motion enhancement could be detected without severe impairment of the image resolution, motion, and color presentation. The CRSMM algorithm significantly improved image quality in terms of motion enhancement. In particular, the pulsation of vascular structures could be displayed more accurately than in EVM. Motion magnification image processing technology has the potential for clinical importance as a video optimizing modality in endoscopic and laparoscopic surgery. Barely detectable (micro)movements can be visualized using this noninvasive marker-free method. Despite these optimistic results, the technology requires considerable further technical development and clinical tests.

Does a birthday predispose to vascular events?

PubMed

Saposnik, Gustavo; Baibergenova, Akerke; Dang, Jason; Hachinski, Vladimir

2006-07-25

To examine the influence of birthdays on the onset and course of vascular events such as stroke, TIA, and acute myocardial infarction (AMI). This population-based study included all emergency department (ED) admissions due to ischemic stroke, TIA, or AMI from April 2002 to March 2004 in Ontario, Canada. All cases were identified through the National Ambulatory Care Reporting System. Calculations of daily and weekly numbers of events were centered on the patient's birthday and the week of the birthday. Statistical analyses include binomial tests and logistic regression. During the study period, there were 24,315 ED admissions with acute stroke, 16,088 with TIAs, and 29,090 with AMI. The observed number of vascular events during the birthday was higher than the expected daily number of visits for stroke (87 vs 67; p = 0.009), TIA (58 vs 44; p = 0.02), and AMI (97 vs 80; p = 0.027) but not for selected control conditions (asthma, appendicitis, head trauma). Vascular events were more likely to occur on birthday (242 vs 191; odds ratio [OR] = 1.27). No significant differences were observed during the birthday week for any of the conditions. Multivariate logistic regression showed that birthday vascular events were more likely to occur in patients with a history of hypertension (OR = 1.88; 95% CI 1.09 to 3.24). Sensitivity analyses with alternative definitions of birthday week did not alter the results. Stress associated with birthdays may trigger vascular events in patients with predisposing conditions.

Vascular closure devices in stroke patients receiving tissue plasminogen activator: A retrospective analysis from an academic tertiary medical center and a teaching community hospital stroke database.

PubMed

Patil, Mangaladevi S; Jayaraman, Mahesh V; Ahn, Sun H

2017-06-01

To determine the safety and effectiveness of vascular closure devices in prevention of access site complications in acute stroke patient receiving intravenous (IV) and/or intra-arterial (IA) IV tissue plasminogen activator (tPA). All patients with acute stroke onset treated with IV and/or IA tPA closed with vascular closure device and adult age (>18 years) were identified from an academic tertiary medical center and a teaching community hospital stroke database for 9 years (from March 2005 to June 2014). A total of 69 patients were included in the study. The mean age was 68.86±16.70 years and 49.2% female. All accesses were under fluoroscopic guidance into the right common femoral artery. We observed a 5.8% complication rate in patients receiving IV and/or IA tPA closed with vascular closure device. Access site complications included 3 cases of hematoma and 1 case of residual oozing. One patient required transfusion due to access site hematoma. Three patients were on aspirin and heparin and 1 was on no prior anticoagulation. Vascular closure device access site hemorrhagic complication rate in those receiving IV and/or IA tPA is low and similar to reported rates in those not receiving thrombolytic therapy. Vascular closure device use in patients receiving thrombolytic therapy is safe and effectively achieves hemostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

H2O2 generated from mitochondrial electron transport chain in thoracic perivascular adipose tissue is crucial for modulation of vascular smooth muscle contraction.

PubMed

Costa, Rafael M; Filgueira, Fernando P; Tostes, Rita C; Carvalho, Maria Helena C; Akamine, Eliana H; Lobato, Nubia S

2016-09-01

The perivascular adipose tissue (PVAT) releases a variety of factors that affect vascular function. PVAT in the thoracic aorta shares characteristics with the brown adipose tissue, including a large amount of mitochondria. PVAT-derived factors influence both endothelial and smooth muscle function via several signaling mechanisms including the release/generation of reactive nitrogen and oxygen species. Considering the importance of reactive oxygen species (ROS) on vascular function and that mitochondria are an important source of ROS, we hypothesized that mitochondria-derived ROS in the PVAT modulates vascular reactivity. Vascular reactivity to norephinephrine (NE) was evaluated in thoracic aortic rings, with or without endothelium and/or PVAT, from male Wistar rats. Mitochondrial uncoupling, as well as hydrogen peroxide (H2O2) removal, increased the contraction in vessels surrounded by PVAT. PVAT stimulated with NE exhibited increased protein expression, determined by Western blot analysis, of manganese superoxide dismutase (Mn-SOD) and decreased protein expression of catalase. Ultimately, NE increased superoxide anion (O2(-)) generation in PVAT via increases in intracellular calcium. These results clearly demonstrate that mitochondrial electron transport chain (mETC) in PVAT contributes to modulation of aortic muscle contraction by generating higher amounts of O2(-) that is, in turn, dismutated to hydrogen peroxide, which then acts as a pivotal signaling molecule regulating vascular smooth muscle contraction. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of vascular variations at cerebellopontine angle by 3D T2WI magnetic-resonance imaging in patients with vertigo.

PubMed

Beyazal Celiker, Fatma; Dursun, Engin; Celiker, Metin; Durakoglugil, Tugba; Beyazal, Mehmet; Inecikli, Mehmet Fatih; Ozgur, Abdulkadir; Terzi, Suat

2017-01-01

Vascular loops of the anterior-inferior cerebellar artery (AICA) at the cerebellopontine angle (CPA) are considered related to auditory-vestibular symptoms. Clinical association of these anatomical aberrations, which can be grouped together as vascular compression syndromes, is controversial. Magnetic resonance imaging (MRI) is widely used to visualize this anatomical region, given its high sensitivity and specificity. To elucidate the clinical relationship of vertigo symptoms with vascular loop compression syndrome by evaluating the neurovascular contacts of the vestibulocochlear nerve (VCN) and AICA at the CPA and internal auditory canal via high-resolution MRI. The study included 417 patients (178 with vertigo and 239 without vertigo) undergoing MRI for various clinical causes. MRI scans were assessed to study the presence of vascular abnormalities at the CPA. According to our findings, type 1 vascular variation was observed most frequently in both sides. MRI findings were similar for the patients with and without vertigo. Identifying the prevalence of the vascular loops of the AICA primarily depends on diagnostic technique, and our results identified a slightly higher prevalence than those of previous studies, which might be partly related to the high-sensitivity of 3-dimensional T2-weighted MRI.

HIV-1, Reactive Oxygen Species and Vascular Complications

PubMed Central

Porter, Kristi M.; Sutliff, Roy L.

2012-01-01

Over 1 million people in the United States and 33 million individuals worldwide suffer from HIV/AIDS. Since its discovery, HIV/AIDS has been associated with an increased susceptibility to opportunistic infection due to immune dysfunction. Highly active antiretroviral therapies (HAART) restore immune function and, as a result, people infected with HIV-1 are living longer. This improved survival of HIV-1 patients has revealed a previously unrecognized risk of developing vascular complications, such as atherosclerosis and pulmonary hypertension. The mechanisms underlying these HIV-associated vascular disorders are poorly understood. However, HIV-induced elevations in reactive oxygen species, including superoxide and hydrogen peroxide, may contribute to vascular disease development and progression by altering cell function and redox-sensitive signaling pathways. In this review, we summarize the clinical and experimental evidence demonstrating HIV- and HIV antiretroviral therapy-induced alterations in reactive oxygen species (ROS) and how these effects likely contribute to vascular dysfunction and disease. PMID:22564529

Vasculature on the clock: Circadian rhythm and vascular dysfunction.

PubMed

Crnko, Sandra; Cour, Martin; Van Laake, Linda W; Lecour, Sandrine

2018-05-17

The master mammalian circadian clock (i.e. central clock), located in the suprachiasmatic nucleus of the hypothalamus, orchestrates the synchronization of the daily behavioural and physiological rhythms to better adapt the organism to the external environment in an anticipatory manner. This central clock is entrained by a variety of signals, the best established being light and food. However, circadian cycles are not simply the consequences of these two cues but are generated by endogenous circadian clocks. Indeed, clock machinery is found in mainly all tissues and cell types, including cells of the vascular system such as endothelial cells, fibroblasts, smooth muscle cells and stem cells. This machinery physiologically contributes to modulate the daily vascular function, and its disturbance therefore plays a major role in the pathophysiology of vascular dysfunction. Therapies targeting the circadian rhythm may therefore be of benefit against vascular disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Mitochondria and Cardiovascular Aging

PubMed Central

Dai, Dao-Fu; Ungvari, Zoltan

2013-01-01

Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (e.g. renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics and exercise training. PMID:22499901

Distribution patterns in the native vascular flora of Iceland.

PubMed

Wasowicz, Pawel; Pasierbiński, Andrzej; Przedpelska-Wasowicz, Ewa Maria; Kristinsson, Hörður

2014-01-01

The aim of our study was to reveal biogeographical patterns in the native vascular flora of Iceland and to define ecological factors responsible for these patterns. We analysed dataset of more than 500,000 records containing information on the occurrence of vascular plants. Analysis of ecological factors included climatic (derived from WORLDCLIM data), topographic (calculated from digital elevation model) and geological (bedrock characteristics) variables. Spherical k-means clustering and principal component analysis were used to detect biogeographical patterns and to study the factors responsible for them. We defined 10 biotic elements exhibiting different biogeographical patterns. We showed that climatic (temperature-related) and topographic variables were the most important factors contributing to the spatial patterns within the Icelandic vascular flora and that these patterns are almost completely independent of edaphic factors (bedrock type). Our study is the first one to analyse the biogeographical differentiation of the native vascular flora of Iceland.

Complications of the access during aortic valve implantation through transfemoral access.

PubMed

Alsac, Jean-Marc; Zegdi, Rachid; Blanchard, Didier; Achouh, Paul; Cholley, Bernard; Berrebi, Alain; Julia, Pierre; Fabiani, Jean-Noël

2011-08-01

Aortic valve implantation (AVI) is a booming therapeutic option in high-risk patients with calcific aortic stenosis. Retrograde femoral approach drawbacks include vascular complications owing to the size of the introduction system (22- and 24-F).The aim of this study was to retrospectively analyze the incidence and the treatment of vascular complications in the first 2 years of transfemoral AVI experience with the first generation of Edwards SAPIEN transcatheter heart valves. Since December 2007, AVI has been performed in 71 patients, 21 times by the transapical route and 50 times by the transfemoral route through an inguinal approach with the first generation of Edwards SAPIEN transcatheter heart valves (23 and 26 mm). The incidence and the treatment of vascular complications were evaluated as main criteria for transfemoral AVI. All the procedures could be successfully performed by a femoral route, except for three cases when the introducing device could not be fixed on the thoracic aorta because of vascular access problems. Vascular access-related complications occurred in nine patients (18%), including three iliac dissections, two aortic dissections, three femoral lesions, and one thoracic aorta rupture. These complications were treated either in a conservative way (n = 2), or in an endovascular way using a contralateral approach (n = 3), or surgically through an inguinal approach (n = 3). A traumatic rupture of the thoracic aorta resulted in the death of a female patient. In our experience, transfemoral AVI gives a satisfying technical success rate in the selected patients. The incidence of complications involving the vascular access remains an important limitation of this new technique. Although a conservative or endovascular treatment can be applied in most cases, improving the introduction devices is highly expected because it would reduce the complications rate of vascular access. Copyright © 2011 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

The interaction of transient receptor potential melastatin 7 with macrophages promotes vascular adventitial remodeling in transverse aortic constriction rats.

PubMed

Li, Yan; Jiang, Hui; Ruan, Chengchao; Zhong, Jiuchang; Gao, Pingjin; Zhu, Dingliang; Niu, Wenquan; Guo, Shujie

2014-01-01

Transient receptor potential melastatin 7 (TRPM7), a novel channel kinase, has been recently identified in the vasculature. However, its regulation and function in vascular diseases remain poorly understood. To address this lack of knowledge, we sought to examine whether TRPM7 can mediate the vascular remodeling process induced by pressure overload in the right common carotid artery proximal to the band (RCCA-B) in male Sprague-Dawley rats with transverse aortic constriction (TAC). The contribution of TRPM7 to amplified vascular remodeling after TAC was tested using morphometric and western blot analyses. Pressure overload-induced vascular wall thickening, especially in the adventitia, was readily detected in RCCA-B. The TRPM7 level was increased with a simultaneous accumulation of macrophages in the adventitia of RCCA-B, whereas the anti-inflammatory molecule annexin-1, a TRPM7 downstream target, was decreased. After the addition of the TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB), significant reductions in macrophage accumulation as well as the expression of monocyte chemotactic protein-1, SM-22-α and collagen I were observed, whereas annexin-1 was rescued. Finally, in cultured vascular adventitial fibroblasts treated with macrophage-conditioned medium, there were marked increases in the expression of TRPM7 and SM-22-α with a concurrent reduction in annexin-1 expression; these effects were largely prevented by treatment with 2-APB and specific anti-TRPM7 small interfering RNA. Our findings provide the first demonstration of the potential regulatory roles of TRPM7 in the vascular inflammation, pressure overload-mediated vascular adventitial collagen accumulation and cell phenotypic transformation in TAC rats. The targeting of TRPM7 has potential therapeutic importance for vascular diseases.