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Sample records for affects vascular function

  1. Hindlimb unweighting affects rat vascular capacitance function

    NASA Technical Reports Server (NTRS)

    Dunbar, S. L.; Tamhidi, L.; Berkowitz, D. E.; Shoukas, A. A.

    2001-01-01

    Microgravity is associated with an impaired stroke volume and, therefore, cardiac output response to orthostatic stress. We hypothesized that a decreased venous filling pressure due to increased venous compliance may be an important contributing factor in this response. We used a constant flow, constant right atrial pressure cardiopulmonary bypass procedure to measure total systemic vascular compliance (C(T)), arterial compliance (C(A)), and venous compliance (C(V)) in seven control and seven 21-day hindlimb unweighted (HLU) rats. These compliance values were calculated under baseline conditions and during an infusion of 0.2 microg*kg(-1)*min(-1) norepinephrine (NE). The change in reservoir volume, which reflects changes in unstressed vascular volume (DeltaV(0)) that occurred upon infusion of NE, was also measured. C(T) and C(V) were larger in HLU rats both at baseline and during the NE infusion (P < 0.05). Infusion of NE decreased C(T) and C(V) by 20% in both HLU and control rats (P < 0.01). C(A) was also significantly decreased in both groups of rats by NE (P < 0.01), but values of C(A) were similar between HLU and control rats both at baseline and during the NE infusion. Additionally, the NE-induced DeltaV(0) was attenuated by 53% in HLU rats compared with control rats (P < 0.05). The larger C(V) and attenuated DeltaV(0) in HLU rats could contribute to a decreased filling pressure during orthostasis and thus may partially underlie the mechanism leading to the exaggerated fall in stroke volume and cardiac output seen in astronauts during an orthostatic stress after exposure to microgravity.

  2. Exposure to Concentrated Ambient Particles Does Not Affect Vascular Function in Patients with Coronary Heart Disease

    PubMed Central

    Mills, Nicholas L.; Robinson, Simon D.; Fokkens, Paul H. B.; Leseman, Daan L. A. C.; Miller, Mark R.; Anderson, David; Freney, Evelyn J.; Heal, Mathew R.; Donovan, Robert J.; Blomberg, Anders; Sandström, Thomas; MacNee, William; Boon, Nicholas A.; Donaldson, Ken; Newby, David E.; Cassee, Flemming R.

    2008-01-01

    Background Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans. Objectives We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. Methods Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables—including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine—6–8 hr after both exposures. Results Particulate concentrations (mean ± SE) in the exposure chamber (190 ± 37 μg/m3) were higher than ambient levels (31 ± 8 μg/m3) and levels in filtered air (0.5 ± 0.4 μg/m3; p < 0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9 ± 8.5 vs. 4.9 ± 1.2 pg/mL, p < 0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p < 0.001 for all), CAPs exposure had no effect on vascular function in either group. Conclusions Despite achieving marked increases in particulate matter, exposure to CAPs—low in combustion-derived particles—did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans. PMID:18560524

  3. Regulatory RNAs controlling vascular (dys)function by affecting TGF-ß family signalling

    PubMed Central

    Kurakula, Kondababu; Goumans, Marie-Jose; ten Dijke, Peter

    2015-01-01

    Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Over the last few years, microRNAs (miRNAs) have emerged as master regulators of gene expression in cardiovascular biology and disease. miRNAs are small endogenous non-coding RNAs that usually bind to 3′ untranslated region (UTR) of their target mRNAs and inhibit mRNA stability or translation of their target genes. miRNAs play a dynamic role in the pathophysiology of many CVDs through their effects on target mRNAs in vascular cells. Recently, numerous miRNAs have been implicated in the regulation of the transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) signalling pathway which plays crucial roles in diverse biological processes, and is involved in pathogenesis of many diseases including CVD. This review gives an overview of current literature on the role of miRNAs targeting TGF-β/BMP signalling in vascular cells, including endothelial cells and smooth muscle cells. We also provide insight into how this miRNA-mediated regulation of TGF-β/BMP signalling might be used to harness CVD. PMID:26862319

  4. [Vascular endothelial Barrier Function].

    PubMed

    Ivanov, A N; Puchinyan, D M; Norkin, I A

    2015-01-01

    Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

  5. TRPV channels and vascular function

    PubMed Central

    Baylie, R.L.; Brayden, J.E.

    2010-01-01

    Transient receptor potential channels, of the vanilloid subtype (TRPV), act as sensory mediators, being activated by endogenous ligands, heat, mechanical and osmotic stress. Within the vasculature, TRPV channels are expressed in smooth muscle cells, endothelial cells, as well as in peri-vascular nerves. Their varied distribution and polymodal activation properties make them ideally suited to a role in modulating vascular function, perceiving and responding to local environmental changes. In endothelial cells, TRPV1 is activated by endocannabinoids, TRPV3 by dietary agonists, and TRPV4 by shear stress, epoxyeicosatrienoic acids (EETs), and downstream of Gq-coupled receptor activation. Upon activation, these channels contribute to vasodilation via nitric oxide (NO), prostacyclin (PGI2), and intermediate/small conductance potassium channel (IKCa/SKCa) dependent pathways. In smooth muscle, TRPV4 is activated by endothelial derived EETs, leading to large conductance potassium channel (BKCa) activation and smooth muscle hyperpolarization. Conversely, smooth muscle TRPV2 channels contribute to global calcium entry and may aid constriction. TRPV1 and TRPV4 are expressed in sensory nerves and can cause vasodilation through CGRP and substance P release as well as mediating vascular function via the baroreceptor reflex (TRPV1) or via increasing sympathetic outflow during osmotic stress (TRPV4). Thus, TRPV channels play important roles in the regulation of normal and pathological cellular function in the vasculature. PMID:21062421

  6. Exercise and vascular function: how much is too much?

    PubMed

    Durand, Matthew J; Gutterman, David D

    2014-07-01

    Exercise is a powerful therapy for preventing the onset of and slowing the progression of cardiovascular disease. Increased shear stress during exercise improves vascular homeostasis by both decreasing reactive oxygen species and increasing nitric oxide bioavailability in the endothelium. While these observations are well accepted as they apply to individuals at risk for cardiovascular disease, less is known about how exercise, especially intense exercise, affects vascular function in healthy individuals. This review highlights examples of how vascular function can paradoxically be impaired in otherwise healthy individuals by extreme levels of exercise, with a focus on the causative role that reactive oxygen species play in this impairment.

  7. Protein Kinase C Inhibitors as Modulators of Vascular Function and Their Application in Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Blood pressure (BP) is regulated by multiple neuronal, hormonal, renal and vascular control mechanisms. Changes in signaling mechanisms in the endothelium, vascular smooth muscle (VSM) and extracellular matrix cause alterations in vascular tone and blood vessel remodeling and may lead to persistent increases in vascular resistance and hypertension (HTN). In VSM, activation of surface receptors by vasoconstrictor stimuli causes an increase in intracellular free Ca2+ concentration ([Ca2+]i), which forms a complex with calmodulin, activates myosin light chain (MLC) kinase and leads to MLC phosphorylation, actin-myosin interaction and VSM contraction. Vasoconstrictor agonists could also increase the production of diacylglycerol which activates protein kinase C (PKC). PKC is a family of Ca2+-dependent and Ca2+-independent isozymes that have different distributions in various blood vessels, and undergo translocation from the cytosol to the plasma membrane, cytoskeleton or the nucleus during cell activation. In VSM, PKC translocation to the cell surface may trigger a cascade of biochemical events leading to activation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK), a pathway that ultimately increases the myofilament force sensitivity to [Ca2+]i, and enhances actin-myosin interaction and VSM contraction. PKC translocation to the nucleus may induce transactivation of various genes and promote VSM growth and proliferation. PKC could also affect endothelium-derived relaxing and contracting factors as well as matrix metalloproteinases (MMPs) in the extracellular matrix further affecting vascular reactivity and remodeling. In addition to vasoactive factors, reactive oxygen species, inflammatory cytokines and other metabolic factors could affect PKC activity. Increased PKC expression and activity have been observed in vascular disease and in certain forms of experimental and human HTN. Targeting of vascular PKC using PKC inhibitors may function in concert with

  8. Vascular smooth muscle phenotypic diversity and function

    PubMed Central

    2010-01-01

    The control of force production in vascular smooth muscle is critical to the normal regulation of blood flow and pressure, and altered regulation is common to diseases such as hypertension, heart failure, and ischemia. A great deal has been learned about imbalances in vasoconstrictor and vasodilator signals, e.g., angiotensin, endothelin, norepinephrine, and nitric oxide, that regulate vascular tone in normal and disease contexts. In contrast there has been limited study of how the phenotypic state of the vascular smooth muscle cell may influence the contractile response to these signaling pathways dependent upon the developmental, tissue-specific (vascular bed) or disease context. Smooth, skeletal, and cardiac muscle lineages are traditionally classified into fast or slow sublineages based on rates of contraction and relaxation, recognizing that this simple dichotomy vastly underrepresents muscle phenotypic diversity. A great deal has been learned about developmental specification of the striated muscle sublineages and their phenotypic interconversions in the mature animal under the control of mechanical load, neural input, and hormones. In contrast there has been relatively limited study of smooth muscle contractile phenotypic diversity. This is surprising given the number of diseases in which smooth muscle contractile dysfunction plays a key role. This review focuses on smooth muscle contractile phenotypic diversity in the vascular system, how it is generated, and how it may determine vascular function in developmental and disease contexts. PMID:20736412

  9. Vascular smooth muscle cell functional contractility depends on extracellular mechanical properties

    PubMed Central

    Steucke, Kerianne E.; Tracy, Paige V.; Hald, Eric S.; Hall, Jennifer L.; Alford, Patrick W.

    2015-01-01

    Vascular smooth muscle cells’ primary function is to maintain vascular homeostasis through active contraction and relaxation. In diseases such as hypertension and atherosclerosis, this function is inhibited concurrent to changes in the mechanical environment surrounding vascular smooth muscle cells. It is well established that cell function and extracellular mechanics are interconnected; variations in substrate modulus affect cell migration, proliferation, and differentiation. To date, it is unknown how the evolving extracellular mechanical environment of vascular smooth muscle cells affects their contractile function. Here, we have built upon previous vascular muscular thin film technology to develop a variable-modulus vascular muscular thin film that measures vascular tissue functional contractility on substrates with a range of pathological and physiological moduli. Using this modified vascular muscular thin film, we found that vascular smooth muscle cells generated greater stress on substrates with higher moduli compared to substrates with lower moduli. We then measured protein markers typically thought to indicate a contractile phenotype in vascular smooth muscle cells and found that phenotype is unaffected by substrate modulus. These data suggest that mechanical properties of vascular smooth muscle cells’ extracellular environment directly influence their functional behavior and do so without inducing phenotype switching. PMID:26283412

  10. Regulation of thrombosis and vascular function by protein methionine oxidation.

    PubMed

    Gu, Sean X; Stevens, Jeff W; Lentz, Steven R

    2015-06-18

    Redox biology is fundamental to both normal cellular homeostasis and pathological states associated with excessive oxidative stress. Reactive oxygen species function not only as signaling molecules but also as redox regulators of protein function. In the vascular system, redox reactions help regulate key physiologic responses such as cell adhesion, vasoconstriction, platelet aggregation, angiogenesis, inflammatory gene expression, and apoptosis. During pathologic states, altered redox balance can cause vascular cell dysfunction and affect the equilibrium between procoagulant and anticoagulant systems, contributing to thrombotic vascular disease. This review focuses on the emerging role of a specific reversible redox reaction, protein methionine oxidation, in vascular disease and thrombosis. A growing number of cardiovascular and hemostatic proteins are recognized to undergo reversible methionine oxidation, in which methionine residues are posttranslationally oxidized to methionine sulfoxide. Protein methionine oxidation can be reversed by the action of stereospecific enzymes known as methionine sulfoxide reductases. Calcium/calmodulin-dependent protein kinase II is a prototypical methionine redox sensor that responds to changes in the intracellular redox state via reversible oxidation of tandem methionine residues in its regulatory domain. Several other proteins with oxidation-sensitive methionine residues, including apolipoprotein A-I, thrombomodulin, and von Willebrand factor, may contribute to vascular disease and thrombosis.

  11. VASCULAR ACTIONS OF ESTROGENS: FUNCTIONAL IMPLICATIONS

    PubMed Central

    Miller, Virginia M.; Duckles, Sue P.

    2009-01-01

    The impact of estrogen exposure in preventing or treating cardiovascular disease is controversial. But it is clear that estrogen has important effects on vascular physiology and pathophysiology, with potential therapeutic implications. Therefore, it is the goal of this review to summarize, using an integrated approach, current knowledge of the vascular effects of estrogen, both in humans and in experimental animals. Aspects of estrogen synthesis and receptors, as well as general mechanisms of estrogenic action are reviewed with an emphasis on issues particularly relevant to the vascular system. Recent understanding of the impact of estrogen on mitochondrial function suggests that the longer lifespan of women compared to men may depend in part on the ability of estrogen to decrease production of reactive oxygen species in mitochondria. Mechanisms by which estrogen increases endothelial vasodilator function, promotes angiogenesis and modulates autonomic function are summarized. Key aspects of the relevant pathophysiology of inflammation, atherosclerosis, stroke, migraine and thrombosis are reviewed concerning current knowledge of estrogenic effects. A number of emerging concepts are addressed throughout. These include the importance of estrogenic formulation and route of administration and the impact of genetic polymorphisms, either in estrogen receptors or in enzymes responsible for estrogen metabolism, on responsiveness to hormone treatment. The importance of local metabolism of estrogenic precursors and the impact of timing for initiation of treatment and its duration are also considered. While consensus opinions are emphasized, controversial views are presented in order to stimulate future research. PMID:18579753

  12. Mechanisms of Microgravity Effect on Vascular Function

    NASA Technical Reports Server (NTRS)

    Purdy, Ralph E.

    1995-01-01

    The overall goal of the project is to characterize the effects of simulated microgravity on vascular function. Microgravity is simulated using the hindlimb unweighted (HU) rat, and the following vessels are removed from HU and paired control rats for in vitro analysis: abdominal aorta, carotid and femoral arteries, jugular and femoral veins. These vessels are cut into 3 mm long rings and mounted in tissue baths for the measurement of either isometric contraction, or relaxation of pre- contracted vessels. The isolated mesenteric vascular bed is perfused for the measurement of changes in perfusion pressure as an index of arteriolar constriction or dilation. This report presents, in addition to the statement of the overall goal of the project, a summary list of the specific hypotheses to be tested. These are followed by sections on results, conclusions, significance and plans for the next year.

  13. Effect of mirthful laughter on vascular function.

    PubMed

    Sugawara, Jun; Tarumi, Takashi; Tanaka, Hirofumi

    2010-09-15

    In contrast to the well-established scientific evidence linking negative emotional states (e.g., depression, anxiety, or anger) to increased risk for cardiovascular disease, much less is known about the association between positive emotional states (e.g., laughter, happiness) and cardiovascular health. We determined the effects of mirthful laughter, elicited by watching comic movies, on endothelial function and central artery compliance. Seventeen apparently healthy adults (23 to 42 years of age) watched 30 minutes of a comedy or a documentary (control) on separate days (crossover design). Heart rate and blood pressure increased significantly while watching the comedy, whereas no such changes were seen while watching the documentary. Ischemia-induced brachial artery flow-mediated vasodilation (by B-mode ultrasound imaging) increased significantly after watching the comedy (17%) and decreased with watching the documentary (-15%). Carotid arterial compliance (by simultaneous application of ultrasound imaging and applanation tonometry) increased (10%) significantly immediately after watching the comedy and returned to baseline 24 hours after the watching, whereas it did not change significantly throughout the documentary condition. Comedy-induced changes in arterial compliance were significantly associated with baseline flow-mediated dilation (r = 0.63). These results suggest that mirthful laughter elicited by comic movies induces beneficial impact on vascular function.

  14. 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.

  15. Melamine Impairs Renal and Vascular Function in Rats

    PubMed Central

    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-01-01

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products. PMID:27324576

  16. Dimethylsulfoxide-soluble smoking particles and nicotine affect vascular contractibility.

    PubMed

    Zhang, Jin-Yan; Cao, Lei; Zheng, Xiao-Hui; Xu, Cang-Bao; Cao, Yong-Xiao

    2009-10-01

    The aim is to study the effect of dimethylsulfoxide-soluble smoking particles (DSP) and nicotine on the contractility of rat mesenteric artery. The superior mesenteric artery segments were cultured with DSP or nicotine for 24 h. The vascular contractibility was recorded with myograph system. DSP 0.4 mL/L and nicotine 0.48 and 0.96 mg/L shifted the concentration-contractile curves induced by sarafotoxin 6c, a selective agonist for ET(B) receptor toward the left with increased E(max). DSP 0.4 mL/L and nicotine 0.96 mg/L shifted ET(A) receptor-mediated the concentration-contractile curves toward the left with increased E(max). However, nicotine 0.06 mg/L which is the equivalent concentration of nicotine in DSP 0.4 mL/L did not affect the curves and the E(max) mediated with ET(A) receptor and ET(B) receptor. DSP 0.2 and 0.4 mL/L shifted the concentration-contractile curves induced by noradrenaline toward the right with decreased E(max). Neither did nicotine 0.06 and 0.96 mg/L. Both DSP and nicotine shifted the concentration-contractile curves induced by 5-hydroxytryptamine (5-HT) toward the right parallely. DSP changed the phenotypes towards an increased efficacy of ET(A) receptor and ET(B) receptor, and a reduced efficacy of 5-HT receptor and alpha-adrenocceptor. The effects of DSP on ET(B) receptor, ET(A) receptor and alpha-adrenocceptor were independent of nicotine. The effect on 5-HT receptor was responsible to nicotine.

  17. The function of vascular endothelial growth factor.

    PubMed

    Nieves, Bonnie J; D'Amore, Patricia A; Bryan, Brad A

    2009-01-01

    Vascular endothelial growth factor (VEGF) is considered the master regulator of angiogenesis during growth and development, as well as in disease states such as cancer, diabetes, and macular degeneration. This review details our current understanding of VEGF signaling and discusses the benefits and unexpected side effects of promising anti-angiogenic therapeutics that are currently being used to inhibit neovacularization in tumors.

  18. Effects of estradiol on uterine perfusion in anesthetized cyclic mares affected with uterine vascular elastosis.

    PubMed

    Esteller-Vico, A; Liu, I K M; Vaughan, B; Steffey, E P; Brosnan, R J

    2016-01-01

    Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares have also been shown to exhibit decreases in uterine blood flow and perfusion of the uterus. Due to the increased thickness of the elastin layers, we hypothesize that vasodilatation of the uterine vasculature is also impaired. To test the functionality of these vessels, we evaluated the vasodilatory effects of estradiol on the uterine vascular bed in mares with normal vasculature and mares with severe elastosis. Both groups were tested in estrus and diestrus. Fluorescent microspheres were used to determine basal blood perfusion, followed by the intravenous administration of 1.0 μg/kg of 17β-estradiol. After 90 min, perfusion was measured once again to determine the vascular response to estradiol. Control mares in estrus displayed a significant increase in total uterine blood flow after the administration of estradiol when compared to baseline levels. No other group had a significant increase in total blood flow and perfusion after estradiol administration. The administration of estradiol in control mares induced regional increases in perfusion in the uterine horns and uterine body during estrus and only in the uterine horns during diestrus. Mares affected by elastosis exhibited no regional differences in perfusion levels post-estradiol administration. The difference in the vasodilatory response induced by estradiol between reproductively healthy mares and mares affected with elastosis indicates that the functionality of the affected vessels is compromised.

  19. Host tree phenology affects vascular epiphytes at the physiological, demographic and community level

    PubMed Central

    Einzmann, Helena J. R.; Beyschlag, Joachim; Hofhansl, Florian; Wanek, Wolfgang; Zotz, Gerhard

    2015-01-01

    The processes that govern diverse tropical plant communities have rarely been studied in life forms other than trees. Structurally dependent vascular epiphytes, a major part of tropical biodiversity, grow in a three-dimensional matrix defined by their hosts, but trees differ in their architecture, bark structure/chemistry and leaf phenology. We hypothesized that the resulting seasonal differences in microclimatic conditions in evergreen vs. deciduous trees would affect epiphytes at different levels, from organ physiology to community structure. We studied the influence of tree leaf phenology on vascular epiphytes on the Island of Barro Colorado, Panama. Five tree species were selected, which were deciduous, semi-deciduous or evergreen. The crowns of drought-deciduous trees, characterized by sunnier and drier microclimates, hosted fewer individuals and less diverse epiphyte assemblages. Differences were also observed at a functional level, e.g. epiphyte assemblages in deciduous trees had larger proportions of Crassulacean acid metabolism species and individuals. At the population level a drier microclimate was associated with lower individual growth and survival in a xerophytic fern. Some species also showed, as expected, lower specific leaf area and higher δ13C values when growing in deciduous trees compared with evergreen trees. As hypothesized, host tree leaf phenology influences vascular epiphytes at different levels. Our results suggest a cascading effect of tree composition and associated differences in tree phenology on the diversity and functioning of epiphyte communities in tropical lowland forests. PMID:25392188

  20. Host tree phenology affects vascular epiphytes at the physiological, demographic and community level.

    PubMed

    Einzmann, Helena J R; Beyschlag, Joachim; Hofhansl, Florian; Wanek, Wolfgang; Zotz, Gerhard

    2014-11-11

    The processes that govern diverse tropical plant communities have rarely been studied in life forms other than trees. Structurally dependent vascular epiphytes, a major part of tropical biodiversity, grow in a three-dimensional matrix defined by their hosts, but trees differ in their architecture, bark structure/chemistry and leaf phenology. We hypothesized that the resulting seasonal differences in microclimatic conditions in evergreen vs. deciduous trees would affect epiphytes at different levels, from organ physiology to community structure. We studied the influence of tree leaf phenology on vascular epiphytes on the Island of Barro Colorado, Panama. Five tree species were selected, which were deciduous, semi-deciduous or evergreen. The crowns of drought-deciduous trees, characterized by sunnier and drier microclimates, hosted fewer individuals and less diverse epiphyte assemblages. Differences were also observed at a functional level, e.g. epiphyte assemblages in deciduous trees had larger proportions of Crassulacean acid metabolism species and individuals. At the population level a drier microclimate was associated with lower individual growth and survival in a xerophytic fern. Some species also showed, as expected, lower specific leaf area and higher δ(13)C values when growing in deciduous trees compared with evergreen trees. As hypothesized, host tree leaf phenology influences vascular epiphytes at different levels. Our results suggest a cascading effect of tree composition and associated differences in tree phenology on the diversity and functioning of epiphyte communities in tropical lowland forests.

  1. Carbon monoxide and bile pigments: surprising mediators of vascular function.

    PubMed

    Durante, William

    2002-08-01

    Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although long considered irrelevant byproducts of heme catabolism, recent studies indicate that CO and the bile pigments biliverdin and bilirubin may play an important physiological role in the circulation. The release of CO by vascular cells may modulate blood flow and blood fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation. CO may also maintain the integrity of the vessel wall by directly blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic inflammatory cytokines from the vessel wall. These effects of CO are mediated via multiple pathways, including activation of soluble guanylate cyclase, potassium channels, p38 mitogen-activated protein kinase, or inhibition of cytochrome P450. In addition, the release of bile pigments may serve to sustain vascular homeostasis by protecting vascular cells from oxidative stress and by inhibiting the adhesion and infiltration of leukocytes into the vessel wall. Induction of HO-1 gene expression and the subsequent release of CO and bile pigments are observed in numerous vascular disorders and may provide an important adaptive mechanism to preserve homeostasis at sites of vascular injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular cells may function as a critical endogenous vasoprotective system. Moreover, pharmacological or genetic approaches targeting HO-1 to the vessel wall may represent a novel therapeutic approach in treating vascular disease.

  2. Melatonin differentially affects vascular blood flow in humans.

    PubMed

    Cook, Jonathan S; Sauder, Charity L; Ray, Chester A

    2011-02-01

    Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial Doppler), arterial blood pressure, and heart rate were measured in 10 healthy subjects (29±1 yr; 5 men and 5 women) in the supine position for 3 min. The protocol began 45 min after the ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the other substance. Melatonin did not alter heart rate and mean arterial pressure. Renal blood flow velocity (RBFV) and renal vascular conductance (RVC) were lower during the melatonin trial compared with placebo (RBFV, 40.5±2.9 vs. 45.4±1.5 cm/s; and RVC, 0.47±0.02 vs. 0.54±0.01 cm·s(-1)·mmHg(-1), respectively). In contrast, forearm blood flow (FBF) and forearm vascular conductance (FVC) were greater with melatonin compared with placebo (FBF, 2.4±0.2 vs. 1.9±0.1 ml·100 ml(-1)·min(-1); and FVC, 0.029±0.003 vs. 0.023±0.002 arbitrary units, respectively). Melatonin did not alter cerebral blood flow measurements compared with placebo. Additionally, phentolamine (5-mg bolus) after melatonin reversed the decrease in RVC, suggesting that melatonin increases sympathetic outflow to the kidney to mediate renal vasoconstriction. In summary, exogenous melatonin differentially alters vascular blood flow in humans. These data suggest the complex nature of melatonin on the vasculature in humans.

  3. Systemic vascular function is associated with muscular power in adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-associated loss of muscular strength and muscular power are critical determinants of loss of physical function and progression to disability in older adults. In this study, we examined the association of systemic vascular function and measures of muscle strength and power in older adults. Measu...

  4. Modulation of vascular cell function by bim expression.

    PubMed

    Morrison, Margaret E; Palenski, Tammy L; Jamali, Nasim; Sheibani, Nader; Sorenson, Christine M

    2013-01-01

    Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM) protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim(-/-)) mice. Bim(-/-) endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim(-/-) endothelial cells with Bim(-/-) pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.

  5. Gap Junctions in the Control of Vascular Function

    PubMed Central

    Duling, Brian R.

    2009-01-01

    Abstract Direct intercellular communication via gap junctions is critical in the control and coordination of vascular function. In the cardiovascular system, gap junctions are made up of one or more of four connexin proteins: Cx37, Cx40, Cx43, and Cx45. The expression of more than one gap-junction protein in the vasculature is not redundant. Rather, vascular connexins work in concert, first during the development of the cardiovascular system, and then in integrating smooth muscle and endothelial cell function, and in coordinating cell function along the length of the vessel wall. In addition, connexin-based channels have emerged as an important signaling pathway in the astrocyte-mediated neurovascular coupling. Direct electrical communication between endothelial cells and vascular smooth muscle cells via gap junctions is thought to play a relevant role in the control of vasomotor tone, providing the signaling pathway known as endothelium-derived hyperpolarizing factor (EDHF). Consistent with the importance of gap junctions in the regulation of vasomotor tone and arterial blood pressure, the expression of connexins is altered in diseases associated with vascular complications. In this review, we discuss the participation of connexin-based channels in the control of vascular function in physiologic and pathologic conditions, with a special emphasis on hypertension and diabetes. Antioxid. Redox Signal. 11, 251–266. PMID:18831678

  6. Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function.

    PubMed

    Terao, Junji

    2017-04-01

    Nowadays dietary flavonoids attract much attention in the prevention of chronic diseases. Epidemiological and intervention studies strongly suggest that flavonoid intake has beneficial effects on vascular health. It is unlikely that flavonoids act as direct antioxidants, although oxidative stress profoundly contributes to vascular impairment leading to cardiovascular diseases. Instead, flavonoids may exert their function by tuning the cellular redox state to an adaptive response or tolerable stress. However, the optimum intake of flavonoids from supplements or diet has not been clarified yet, because a number of exogenous and endogenous factors modulating their bioavailability affect their vascular function. This review will focus on the current knowledge of the bioavailability and vascular function of quercetin as a representative of antioxidative flavonoids. Current intervention studies imply that intake of quercetin-rich onion improves vascular health. Onion may be superior to quercetin supplement from the viewpoint of quercetin bioavailability, probably because the food matrix enhances the intestinal absorption of quercetin. α-Glucosylation increases its bioavailability by elevating the accessibility to the absorptive cells. Prenylation may enhance bioaccumulation at the target site by increasing the cellular uptake. However, these chemical modifications do not guarantee health benefits to the vascular system. Dietary quercetin is exclusively present as their conjugated form in the blood stream. Quercetin may exert its vascular function as an aglycone within macrophage cells after inflammation-induced deconjugation and as conjugated metabolites by targeting endothelial cells. The relationship between the bioavailability and bio-efficacy should be clarified, to evaluate the vascular function of a wide variety of dietary flavonoids.

  7. Vascular function and short-term exposure to fine particulate air pollution.

    PubMed

    Pope, C Arden; Hansen, Jaron C; Kuprov, Roman; Sanders, Matthew D; Anderson, Michael N; Eatough, Delbert J

    2011-08-01

    Exposure to fine particulate air pollution has been implicated as a risk factor for cardiopulmonary disease and mortality. Proposed biological pathways imply that particle-induced pulmonary and systemic inflammation play a role in activating the vascular endothelium and altering vascular function. Potential effects of fine particulate pollution on vascular function are explored using controlled chamber exposure and uncontrolled ambient exposure. Research subjects included four panels with a total of 26 healthy nonsmoking young adults. On two study visits, at least 7 days apart, subjects spent 3 hr in a controlled-exposure chamber exposed to 150-200 microg/m3 of fine particles generated from coal or wood combustion and 3 hr in a clean room, with exposure and nonexposure periods alternated between visits. Baseline, postexposure, and post-clean room reactive hyperemia-peripheral arterial tonometry (RH-PAT) was conducted. A microvascular responsiveness index, defined as the log of the RH-PAT ratio, was calculated. There was no contemporaneous vascular response to the few hours of controlled exposure. Declines in vascular response were associated with elevated ambient exposures for the previous 2 days, especially for female subjects. Cumulative exposure to real-life fine particulate pollution may affect vascular function. More research is needed to determine the roles of age and gender, the effect of pollution sources, the importance of cumulative exposure over a few days versus a few hours, and the lag time between exposure and response.

  8. Pioglitazone does not affect vascular or inflammatory responses after endotoxemia in humans.

    PubMed

    Schaller, G; Kolodjaschna, J; Pleiner, J; Mittermayer, F; Kapiotis, S; Schmetterer, L; Wolzt, M

    2008-08-01

    PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.

  9. Engineering of human hepatic tissue with functional vascular networks.

    PubMed

    Takebe, Takanori; Koike, Naoto; Sekine, Keisuke; Fujiwara, Ryoji; Amiya, Takeru; Zheng, Yun-Wen; Taniguchi, Hideki

    2014-01-01

    Although absolute organ shortage highlights the needs of alternative organ sources for regenerative medicine, the generation of a three-dimensional (3D) and complex vital organ, such as well-vascularized liver, remains a challenge. To this end, tissue engineering holds great promise; however, this approach is significantly limited by the failure of early vascularization in vivo after implantation. Here, we established a stable 3D in vitro pre-vascularization platform to generate human hepatic tissue after implantation in vivo. Human fetal liver cells (hFLCs) were mixed with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (hMSCs) and were implanted into a collagen/fibronectin matrix composite that was used as a 3-D carrier. After a couple of days, the fluorescent HUVECs developed premature vascular networks in vitro, which were stabilized by hMSCs. The establishment of functional vessels inside the pre-vascularized constructs was proven using dextran infusion studies after implantation under a transparency cranial window. Furthermore, dynamic morphological changes during embryonic liver cell maturation were intravitaly quantified with high-resolution confocal microscope analysis. The engineered human hepatic tissue demonstrated multiple liver-specific features, both structural and functional. Our new techniques discussed here can be implemented in future clinical uses and industrial uses, such as drug testing.

  10. Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function.

    PubMed

    Serini, Guido; Valdembri, Donatella; Zanivan, Sara; Morterra, Giulia; Burkhardt, Constanze; Caccavari, Francesca; Zammataro, Luca; Primo, Luca; Tamagnone, Luca; Logan, Malcolm; Tessier-Lavigne, Marc; Taniguchi, Masahiko; Püschel, Andreas W; Bussolino, Federico

    2003-07-24

    The motility and morphogenesis of endothelial cells is controlled by spatio-temporally regulated activation of integrin adhesion receptors, and integrin activation is stimulated by major determinants of vascular remodelling. In order for endothelial cells to be responsive to changes in activator gradients, the adhesiveness of these cells to the extracellular matrix must be dynamic, and negative regulators of integrins could be required. Here we show that during vascular development and experimental angiogenesis, endothelial cells generate autocrine chemorepulsive signals of class 3 semaphorins (SEMA3 proteins) that localize at nascent adhesive sites in spreading endothelial cells. Disrupting endogenous SEMA3 function in endothelial cells stimulates integrin-mediated adhesion and migration to extracellular matrices, whereas exogenous SEMA3 proteins antagonize integrin activation. Misexpression of dominant negative SEMA3 receptors in chick embryo endothelial cells locks integrins in an active conformation, and severely impairs vascular remodelling. Sema3a null mice show vascular defects as well. Thus during angiogenesis endothelial SEMA3 proteins endow the vascular system with the plasticity required for its reshaping by controlling integrin function.

  11. Adenosine promotes vascular barrier function in hyperoxic lung injury

    PubMed Central

    Davies, Jonathan; Karmouty‐Quintana, Harry; Le, Thuy T.; Chen, Ning‐Yuan; Weng, Tingting; Luo, Fayong; Molina, Jose; Moorthy, Bhagavatula; Blackburn, Michael R.

    2014-01-01

    Abstract Hyperoxic lung injury is characterized by cellular damage from high oxygen concentrations that lead to an inflammatory response in the lung with cellular infiltration and pulmonary edema. Adenosine is a signaling molecule that is generated extracellularly by CD73 in response to injury. Extracellular adenosine signals through cell surface receptors and has been found to be elevated and plays a protective role in acute injury situations. In particular, ADORA2B activation is protective in acute lung injury. However, little is known about the role of adenosine signaling in hyperoxic lung injury. We hypothesized that hyperoxia‐induced lung injury leads to CD73‐mediated increases in extracellular adenosine, which is protective through ADORA2B signaling pathways. To test this hypothesis, we exposed C57BL6, CD73−/−, and Adora2B−/− mice to 95% oxygen or room air and examined markers of pulmonary inflammation, edema, and monitored lung histology. Hyperoxic exposure caused pulmonary inflammation and edema in association with elevations in lung adenosine levels. Loss of CD73‐mediated extracellular adenosine production exacerbated pulmonary edema without affecting inflammatory cell counts. Furthermore, loss of the ADORA2B had similar results with worsening of pulmonary edema following hyperoxia exposure without affecting inflammatory cell infiltration. This loss of barrier function correlated with a decrease in occludin in pulmonary vasculature in CD73−/− and Adora2B−/− mice following hyperoxia exposure. These results demonstrate that exposure to a hyperoxic environment causes lung injury associated with an increase in adenosine concentration, and elevated adenosine levels protect vascular barrier function in hyperoxic lung injury through the ADORA2B‐dependent regulation of occludin. PMID:25263205

  12. Green tea (Camellia sinensis) catechins and vascular function.

    PubMed

    Moore, Rosalind J; Jackson, Kim G; Minihane, Anne M

    2009-12-01

    The health benefits of green tea (Camellia sinensis) catechins are becoming increasingly recognised. Amongst the proposed benefits are the maintenance of endothelial function and vascular homeostasis and an associated reduction in atherogenesis and CVD risk. The mounting evidence for the influential effect of green tea catechins on vascular function from epidemiological, human intervention and animal studies is subject to review together with exploration of the potential mechanistic pathways involved. Epigallocatechin-3-gallate, one of the most abundant and widely studied catechin found in green tea, will be prominent in the present review. Since there is a substantial inconsistency in the published data with regards to the impact of green tea catechins on vascular function, evaluation and interpretation of the inter- and intra-study variability is included. In conclusion, a positive effect of green tea catechins on vascular function is becoming apparent. Further studies in animal and cell models using physiological concentrations of catechins and their metabolites are warranted in order to gain some insight into the physiology and molecular basis of the observed beneficial effects.

  13. Potential benefits of exercise on blood pressure and vascular function.

    PubMed

    Pal, Sebely; Radavelli-Bagatini, Simone; Ho, Suleen

    2013-01-01

    Physical activity seems to enhance cardiovascular fitness during the course of the lifecycle, improve blood pressure, and is associated with decreased prevalence of hypertension and coronary heart disease. It may also delay or prevent age-related increases in arterial stiffness. It is unclear if specific exercise types (aerobic, resistance, or combination) have a better effect on blood pressure and vascular function. This review was written based on previous original articles, systematic reviews, and meta-analyses indexed on PubMed from years 1975 to 2012 to identify studies on different types of exercise and the associations or effects on blood pressure and vascular function. In summary, aerobic exercise (30 to 40 minutes of training at 60% to 85% of predicted maximal heart rate, most days of the week) appears to significantly improve blood pressure and reduce augmentation index. Resistance training (three to four sets of eight to 12 repetitions at 10 repetition maximum, 3 days a week) appears to significantly improve blood pressure, whereas combination exercise training (15 minutes of aerobic and 15 minutes of resistance, 5 days a week) is beneficial to vascular function, but at a lower scale. Aerobic exercise seems to better benefit blood pressure and vascular function.

  14. Vascular function in diabetic individuals in association with particulate matter

    EPA Science Inventory

    Rationale: Exposure to ambient air pollution has been shown to be associated with cardiovascular effects, especially in people with chronic diseases such as diabetes. The purpose of this study was to analyze the short-term effects of air pollution on vascular function in two pane...

  15. Functional imaging of tumor vascular network in small animal models

    NASA Astrophysics Data System (ADS)

    Kalchenko, Vyacheslav; Madar-Balakirski, Noa; Kuznetsov, Yuri; Meglinski, Igor; Harmelin, Alon

    2011-07-01

    In current report we present synchronized in vivo imaging of tumor vascular network and tumor microenvironment obtained by combined use of Dynamic Light Scattering Imaging, Spectrally Enhanced Microscopy, and Fluorescence Intravital Microscopy. Dynamic Light Scattering Imaging is used for functional imaging of the vascular network and blood microcirculation. Spectrally Enhanced Microscopy provides information regarding blood vessel topography. Fluorescence Intravital Microscopy is used for imaging of tumor microvasculature and tumor microenvironment. These well known modalities have been comprehensively validated in the past and are widely used in various bio-medical applications. As shown here, their combined application has great potential for studies of vascular biology. This multi-modal non-invasive diagnostic technique expands our current capacity to investigate blood microcirculation and tumor angiogenesis in vivo, thereby contributing to the development of cancer research and treatment.

  16. The plant vascular system: evolution, development and functions.

    PubMed

    Lucas, William J; Groover, Andrew; Lichtenberger, Raffael; Furuta, Kaori; Yadav, Shri-Ram; Helariutta, Ykä; He, Xin-Qiang; Fukuda, Hiroo; Kang, Julie; Brady, Siobhan M; Patrick, John W; Sperry, John; Yoshida, Akiko; López-Millán, Ana-Flor; Grusak, Michael A; Kachroo, Pradeep

    2013-04-01

    The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased stature, photosynthetic output, and ability to colonize a greatly expanded range of environmental habitats. Recently, considerable progress has been made in terms of our understanding of the developmental and physiological programs involved in the formation and function of the plant vascular system. In this review, we first examine the evolutionary events that gave rise to the tracheophytes, followed by analysis of the genetic and hormonal networks that cooperate to orchestrate vascular development in the gymnosperms and angiosperms. The two essential functions performed by the vascular system, namely the delivery of resources (water, essential mineral nutrients, sugars and amino acids) to the various plant organs and provision of mechanical support are next discussed. Here, we focus on critical questions relating to structural and physiological properties controlling the delivery of material through the xylem and phloem. Recent discoveries into the role of the vascular system as an effective long-distance communication system are next assessed in terms of the coordination of developmental, physiological and defense-related processes, at the whole-plant level. A concerted effort has been made to integrate all these new findings into a comprehensive picture of the state-of-the-art in the area of plant vascular biology. Finally, areas important for future research are highlighted in terms of their likely contribution both to basic knowledge and applications to primary industry.

  17. BP and Vascular Function Following Space Flight

    NASA Technical Reports Server (NTRS)

    Hatton, Daniel C.; Yue, Qi; Chapman, Justin; Xue, Hong; Dierickx, Jacqueline; Roullet, Chantal; Roullet, Jean-Baptiste; Phanouvong, Thongchanh; Watanabe, Mitsuaki; Otsuka, Keiichi; McCarron, David A.

    1997-01-01

    Blood pressure and mesenteric resistance artery function were assessed in 9-week-old spontaneously hypertensive rats following an 18 day shuttle flight on STS-80. Blood pressure was measured twice, first in conscious animals using a tail-cuff method and then while the animals were anesthetized with 2% halothane in O2. Isolated mesenteric resistance artery responses to cumulative additions of norepinephrine, acetylcholine, sodium nitroprusside, and calcium were measured within 17 hours of landing using wire myography. Blood pressure was slightly reduced in conscious animals following flight (p=0.056) but was significantly elevated (p less than.001) above vivarium control group values in anesthetized animals. Maximal contraction of mesenteric arteries to norepinephrine was attenuated in the flight animals (p less than.001)aswasrelaxationtoacetylcholine(p less than .001)andcalcium(p less than .05). There was no difference between flight and control animals in the vessel response to sodium nitroprusside (p greater than .05). The results suggest that there may have been an increase in synthesis and release of nitric oxide in the flight animals.

  18. The COP9 signalosome and vascular function: intriguing possibilities?

    PubMed Central

    Martin, Douglas S; Wang, Xuejun

    2015-01-01

    Disorders of vascular function contribute importantly to cardiovascular disease which represents a substantial cause of morbidity and mortality worldwide. An emerging paradigm in the study of cardiovascular diseases is that protein ubiquitination and turnover represent key pathological mechanisms. Our understanding of these processes in the vasculature is growing but remains incomplete. Since protein ubiquitination and turnover can represent a terminal event in the life of a given protein, entry into these pathways must be highly regulated. However, at present understanding of these regulatory mechanisms, particularly in the vasculature, is fragmentary. The COP9 (constitutive photomorphogenic mutant 9) signalosome (CSN) is a heteromeric protein complex implicated in the control of protein degradation. The CSN participates critically in the control of Cullin Ring Ligases (CRLs), at least in part via the detachment of a small protein, Nedd8 (deneddylation). CRLs are one of the largest groups of ubiquitin ligases, which represent the most selective control point for protein ubiquitination. Thus, the CSN by virtue of its ability to control the CRLs ubiquitin ligase activity is ideally positioned to effect selective modulation of protein turnover. This review surveys currently available data regarding the potential role of the CSN in control of vascular function. Data potentially linking the CSN to control of regulatory proteins involved in vascular smooth muscle proliferation and to vascular smooth muscle contraction are presented with the intent of providing potentially intriguing possibilities for future investigation. PMID:26064791

  19. Bioelectric impact of pathological angiogenesis on vascular function

    PubMed Central

    Puro, Donald G.; Kohmoto, Ryohsuke; Fujita, Yasushi; Gardner, Thomas W.; Padovani-Claudio, Dolly A.

    2016-01-01

    Pathological angiogenesis, as seen in many inflammatory, immune, malignant, and ischemic disorders, remains an immense health burden despite new molecular therapies. It is likely that further therapeutic progress requires a better understanding of neovascular pathophysiology. Surprisingly, even though transmembrane voltage is well known to regulate vascular function, no previous bioelectric analysis of pathological angiogenesis has been reported. Using the perforated-patch technique to measure vascular voltages in human retinal neovascular specimens and rodent models of retinal neovascularization, we discovered that pathological neovessels generate extraordinarily high voltage. Electrophysiological experiments demonstrated that voltage from aberrantly located preretinal neovascular complexes is transmitted into the intraretinal vascular network. With extensive neovascularization, this voltage input is substantial and boosts the membrane potential of intraretinal blood vessels to a suprahyperpolarized level. Coincident with this suprahyperpolarization, the vasomotor response to hypoxia is fundamentally altered. Instead of the compensatory dilation observed in the normal retina, arterioles constrict in response to an oxygen deficiency. This anomalous vasoconstriction, which would potentiate hypoxia, raises the possibility that the bioelectric impact of neovascularization on vascular function is a previously unappreciated pathophysiological mechanism to sustain hypoxia-driven angiogenesis. PMID:27551068

  20. Maternal Hyperleptinemia Is Associated with Male Offspring’s Altered Vascular Function and Structure in Mice

    PubMed Central

    Pollock, Kelly E.; Talton, Omonseigho O.; Foote, Christopher A.; Reyes-Aldasoro, Constantino C.; Wu, Ho-Hsiang; Ji, Tieming; Martinez-Lemus, Luis A.; Schulz, Laura C.

    2016-01-01

    Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Leprdb/+ dams were compared to genotype matched offspring of WT-control dams. Vascular function was assessed in male offspring at 6, and at 31 weeks of age after half the offspring had been fed a high fat, high sucrose diet (HFD) for 6 weeks. Blood pressure was increased by HFD but not affected by maternal hyperleptinemia. On a standard diet, offspring of hyperleptinemic dams had outwardly remodeled mesenteric arteries and an enhanced vasodilatory response to insulin. In offspring of WT but not Leprdb/+ dams, HFD induced vessel hypertrophy and enhanced vasodilatory responses to acetylcholine, while HFD reduced insulin responsiveness in offspring of hyperleptinemic dams. Offspring of hyperleptinemic dams had stiffer arteries regardless of diet. Therefore, while maternal hyperleptinemia was largely beneficial to offspring vascular health under a standard diet, it had detrimental effects in offspring fed HFD. These results suggest that circulating maternal leptin concentrations may interact with other factors in the pre- and post -natal environments to contribute to altered vascular function in offspring of diabetic pregnancies. PMID:27187080

  1. Enzymatic regulation of functional vascular networks using gelatin hydrogels

    PubMed Central

    Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M.; Chen, Ying-Chieh

    2015-01-01

    To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues. PMID:25749296

  2. Enzymatic regulation of functional vascular networks using gelatin hydrogels.

    PubMed

    Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

    2015-06-01

    To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

  3. Plasma inflammatory and vascular homeostasis biomarkers increase during human pregnancy but are not affected by oily fish intake.

    PubMed

    García-Rodríguez, Cruz E; Olza, Josune; Aguilera, Concepción M; Mesa, María D; Miles, Elizabeth A; Noakes, Paul S; Vlachava, Maria; Kremmyda, Lefkothea-Stella; Diaper, Norma D; Godfrey, Keith M; Calder, Philip C; Gil, Angel

    2012-07-01

    The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P < 0.001), whereas plasma matrix metalloproteinase 9, IL-6, TNFα, and nerve growth factor concentrations were not affected. Vascular homeostasis biomarkers soluble E-selectin, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule (sICAM)-1, and total plasminogen activator inhibitor-1 increased as pregnancy progressed (P < 0.001). The plasma sICAM-1 concentration was greater in the control group than in the salmon group at wk 20 (baseline) and 38 (P = 0.007) but there was no group x time interaction, and when baseline concentration was used as a covariate, the groups did not differ (P = 0.69). The remaining biomarkers analyzed were similar in both groups. Therefore, although some inflammatory and vascular homeostasis biomarkers change during pregnancy, they are not affected by the increased intake of farmed salmon.

  4. Vascular dilatory functions of ovo-lactovegetarians compared with omnivores.

    PubMed

    Lin, C L; Fang, T C; Gueng, M K

    2001-09-01

    Vegetarians have lower blood pressure and lower cardiovascular mortality. Vegetarian diets may have lower cardiovascular risks through positive influence on endothelium-dependent relaxation and related functions. The objectives of this study were to assess the differences of vascular dilatory functions between middle-aged vegetarians and sex and age-matched omnivores before they develop any clinical manifestations of atherosclerosis. Twenty healthy vegetarians over the age of 50 and 20 healthy omnivores over the age of 50 were recruited for this study. Subjects with known risk factors for atherosclerosis such as hypertension, diabetes, obesity, hypercholesteremia, cigarette smoking, family history of vascular diseases, or taking any regular medication were excluded. Medical history, body weight, height, and duration of vegetarian diet were recorded. Baseline CBC, urinalysis and biochemical data such as fasting blood glucose, thyroid function, blood urea nitrogen, creatinine, serum electrolytes (sodium, potassium, chloride, calcium and magnesium), lipid profiles [total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol] were obtained after a 14 h fast. Blood pressures and heart rate were recorded in supine position. Vascular dilatory functions, both flow-mediated (endothelium-dependent) and nitroglycerin-induced (endothelium-independent), were evaluated by using a non-invasive ultrasonographic method. The results show that there were no significant differences in the baseline characteristic between the vegetarians and the omnivores. There were also no significant differences in serum glucose, lipid profiles and thyroid function between these two groups. However, vasodilatation responses (both flow-mediated and nitroglycerin-induced) were significantly better in the vegetarian group and the degree of vasodilatation appeared to be correlated with years on vegetarian diets. Our findings suggest that

  5. Role of endothelin in uteroplacental circulation and fetal vascular function.

    PubMed

    Paradis, Alexandra; Zhang, Lubo

    2013-09-01

    Endothelins are 21-amino acid peptides involved in vascular homeostasis. Three types of peptide have been identified, with endothelin-1 (ET-1) being the most potent vasoconstrictor currently known. Two endothelin receptor subtypes are found in various tissues, including the brain, heart, blood vessel, lung, and placenta. The ETA-receptor is associated with vasoconstriction in vascular smooth muscle. Conversely, the ETB-receptor can elicit a vasoconstrictor effect in vascular smooth muscle and a vasodilator effect via its action in endothelial cells. Both receptors play a key role in maintaining circulatory homeostasis and vascular function. Changes in ET-1 expression are found in various disease states, and overexpression of ET-1 is observed in hypertension and preeclampsia in pregnancy. Placental localization of ET-1 implies a key role in regulating the uteroplacental circulation. Additionally, ET-1 is important in the fetal circulation and is involved in the pulmonary circulation and closure of the ductus arteriosus after birth, as well as fetal growth constriction in utero. ET receptor antagonists and nitric oxide donors may provide therapeutic potential in treating conditions associated with overexpression of ET and hypertension.

  6. Nitrites derived from Foneiculum vulgare (fennel) seeds promotes vascular functions.

    PubMed

    Swaminathan, Akila; Sridhara, Sree Rama Chaitanya; Sinha, Swaraj; Nagarajan, Shunmugam; Balaguru, Uma Maheswari; Siamwala, Jamila H; Rajendran, Saranya; Saran, Uttara; Chatterjee, Suvro

    2012-12-01

    Recent evidence has demonstrated that nitrites play an important role in the cardiovascular system. Fennel (Foneiculum vulgare) seeds are often used as mouth fresheners after a meal in both the Indian sub-continent and around the world. The present study aims to quantify the nitrite and nitrates in fennel seeds as well as elucidating the effect of fennel derived-nitrites on vascular functions. Results from our study show that fennel seeds contain significantly higher amount of nitrites when compared to other commonly used post-meal seeds. Furthermore our study confirmed the functional effects of fennel derived-nitrites using in vitro and ex vivo models that describe the promotion of angiogenesis, cell migration, and vasorelaxation. We also showed that chewing fennel seeds enhanced nitrite content of saliva. Thus our study indicates the potential role of fennel derived-nitrites on the vascular system.

  7. The extraction of vascular axis based on signed distance function

    NASA Astrophysics Data System (ADS)

    Hong, Qingqi; Chen, Liyan; Wang, Beizhan; Wu, Qingqiang

    2014-01-01

    This paper presents a simple and fast algorithm to extract the skeleton of vascular structures from segmented vessel datasets. Our algorithm is based on a step by step approach to move a small volume of interest along the vessel tree. With the introduction of Signed Distance Function (SDF), the moving sphere along the vessel tree can easily and automatically detect bifurcations and predict the location of next axis point. Some experiments have been carried out to demonstrate the strengths of our proposed method.

  8. Functional vascular diseases: Raynaud's syndrome, acrocyanosis and erythromelalgia.

    PubMed

    Heidrich, H

    2010-02-01

    Raynauds syndrome, acrocyanosis and erythromelalgia are functional vascular diseases that differ with respect to prevalence, clinical picture, therapy, prognosis, and impairment of quality of life. Raynauds syndrome occurs in 5 to 20 % of the population in Europe, is observed four times more often in women than in men and appears first at the age of 40 (3 to 80), on the average. Raynauds attacks are characterized by a paroxysmal white-blue-red or just white and blue discoloration of the fingers and toes; the attacks are induced by cold or stress, usually, cease after no more than some minutes (average 23 min.), but can also persist for hours. A distinction must be made between primary (aetiology unknown), secondary (aetiology known) and suspected secondary Raynauds syndromes (causal underlying disease suspected). There are several different therapy options, but not all of them have been substantiated by evidence. Acrocyanosis is rarer than Raynauds syndrome, and contrary to the latter, is characterized by nonparoxysmal, in most cases persistent, painless bluish-red symmetrical discolorations of the hands, feet and knees. It is more frequent in women than in men and becomes manifest before the 25th year of age, on the average (15th to 70th year of age). A distinction is made between primary acrocyanosis without detectable underlying disease and secondary acrocyanosis with a specific underlying disease. No effective therapy for primary acrocyanosis is known, but secondary forms can sometimes be treated. Patients with primary and secondary erythromelalgia, a very rare condition, sustain paroxysmal burning pain with marked reddening of the legs, feet and less often the hands. The attacks are triggered by warmth. Women are affected more often than men. The age of first manifestation is 40 to 55 years, but the first attacks may just as well occur during childhood. There are different therapeutic approaches with occasional success, but no general recommendations.

  9. Gender Differences in Bed Rest: Preliminary Analysis of Vascular Function

    NASA Technical Reports Server (NTRS)

    Platts, Steven H.; Stenger, Michael B.; Martin, David S.; Freeman-Perez, Sondra A.; Phillips, Tiffany; Ribeiro, L. Christine

    2008-01-01

    Orthostatic intolerance is a recognized consequence of spaceflight. Numerous studies have shown that women are more susceptible to orthostatic intolerance following spaceflight as well as bed rest, the most commonly used ground-based analog for spaceflight. One of the possible mechanisms proposed to account for this is a difference in vascular responsiveness between genders. We hypothesized that women and men would have differing vascular responses to 90 days of 6-degree head down tilt bed rest. Additionally, we hypothesized that vessels in the upper and lower body would respond differently, as has been shown in the animal literature. Thirteen subjects were placed in bedrest for 90 days (8 men, 5 women) at the Flight Analogs Unit, UTMB. Direct arterial and venous measurements were made with ultrasound to evaluate changes in vascular structure and function. Arterial function was assessed, in the arm and leg, during a reactive hyperemia protocol and during sublingual nitroglycerin administration to gauge the contributions of endothelial dependent and independent dilator function respectively. Venous function was assessed in dorsal hand and foot veins during the administration of pharmaceuticals to assess constrictor and dilator function. Both gender and day effects are seen in arterial dilator function to reactive hyperemia, but none are seen with nitroglycerin. There are also differences in the wall thickness in the arm vs the leg during bed rest, which return toward pre-bed rest levels by day 90. More subjects are required, especially females as there is not sufficient power to properly analyze venous function. Day 90 data are most underpowered.

  10. Complex treatment of trophic affections with vascular patients using monochromatic red light and hyperbaric oxygenation

    NASA Astrophysics Data System (ADS)

    Babkina, Zinaida M.; Vasilyev, Mikhail V.; Zakharov, Vyacheslav P.; Nikolayev, Viktor V.; Babkin, Vasily I.; Samoday, Valery G.; Zon, Boris A.; Pakhomov, Gennady V.; Naskidashvili, Vasily I.; Kumin, Anatoly A.

    1996-11-01

    Monochromatic red light irradiation therapy of trophic skin affections with vascular patients permits to receive positive results with small wounds. A combination of monochromatic red light and hyperbaric oxygenation is most perspective when conducting a complex therapy of trophic wounds not more than 40 mm2 and allows to diminish time of treatment almost two times.

  11. Uteroplacental circulation and fetal vascular function and development.

    PubMed

    Thornburg, Kent L; Louey, Samantha

    2013-09-01

    Although blood flow in the placental vasculature is governed by the same physiological forces of shear, pressure and resistance as in other organs, it is also uniquely specialized on the maternal and fetal sides. At the materno-fetal interface, the independent uteroplacental and umbilicoplacental circulations must coordinate sufficiently to supply the fetus with the nutrients and substrates it needs to grow and develop. Uterine arterial flow must increase dramatically to accommodate the growing fetus. Recent evidence delineates the hormonal and endothelial mechanisms by which maternal vessels dilate and remodel during pregnancy. The umbilical circulation is established de novo during embryonic development but blood does not flow through the placenta until late in the first trimester. The umbilical circulation operates in the interest of maintaining fetal oxygenation over the course of pregnancy, and is affected differently by mechanical and chemical regulators of vascular tone compared to other organs. The processes that match placental vascular growth and fetal tissue growth are not understood, but studies of compromised pregnancies provide clues. The subtle changes that cause the failure of the normally regulated vascular processes during pregnancy have not been thoroughly identified. Likewise, practical and effective therapeutic strategies to reverse detrimental placental perfusion patterns have yet to be investigated.

  12. Serial assessment of local peripheral vascular function after eccentric exercise.

    PubMed

    Stacy, Mitchel R; Bladon, Kallie J; Lawrence, Jennifer L; McGlinchy, Sarah A; Scheuermann, Barry W

    2013-12-01

    Muscle damage is a common response to unaccustomed eccentric exercise; however, the effects of skeletal muscle damage on local vascular function and blood flow are poorly understood. This study examined serial local vascular responses to flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) dilation in the brachial artery after strenuous eccentric exercise and serially assessed resting blood flow. Ten healthy males performed 50 maximal eccentric unilateral arm contractions to induce muscle damage to the biceps brachii. Changes in maximal isometric strength and vascular responses were assessed 1, 24, 48, and 96 h after exercise. Mean blood velocities and arterial diameters, measured with Doppler ultrasound, were used to calculate blood flow and shear stress (expressed as area under the curve). Eccentric exercise resulted in impaired maximal isometric strength for up to 96 h (p < 0.001). Reductions in flow-mediated dilation (before exercise, 9.4% ± 2.6%; 1 h after exercise, 5.1% ± 2.2%) and nitroglycerin responses (before exercise, 26.3% ± 6.5%; 1 h after exercise, 20.7% ± 4.7%) were observed in the 1 h after exercise and remained lower for 96 h (p < 0.05). The shear stress response was attenuated immediately after exercise and remained impaired for 48 h (p < 0.05). Resting blood pressure and muscle blood flow remained similar throughout the study. Results suggest that muscle damage from eccentric exercise leads to impaired local endothelial and vascular smooth muscle function. Lower shear stress after exercise might contribute to the observed reduction in flow-mediated dilation responses, but the mechanism responsible for the attenuated endothelial-independent vasodilation remains unclear.

  13. Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function.

    PubMed

    Hall, Wendy L

    2009-06-01

    The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.

  14. Diverse Functions of Retinoic Acid in Brain Vascular Development

    PubMed Central

    Bonney, Stephanie; Harrison-Uy, Susan; Mishra, Swati; MacPherson, Amber M.; Choe, Youngshik; Li, Dan; Jaminet, Shou-Ching; Fruttiger, Marcus; Pleasure, Samuel J.

    2016-01-01

    As neural structures grow in size and increase metabolic demand, the CNS vasculature undergoes extensive growth, remodeling, and maturation. Signals from neural tissue act on endothelial cells to stimulate blood vessel ingression, vessel patterning, and acquisition of mature brain vascular traits, most notably the blood–brain barrier. Using mouse genetic and in vitro approaches, we identified retinoic acid (RA) as an important regulator of brain vascular development via non-cell-autonomous and cell-autonomous regulation of endothelial WNT signaling. Our analysis of globally RA-deficient embryos (Rdh10 mutants) points to an important, non-cell-autonomous function for RA in the development of the vasculature in the neocortex. We demonstrate that Rdh10 mutants have severe defects in cerebrovascular development and that this phenotype correlates with near absence of endothelial WNT signaling, specifically in the cerebrovasculature, and substantially elevated expression of WNT inhibitors in the neocortex. We show that RA can suppress the expression of WNT inhibitors in neocortical progenitors. Analysis of vasculature in non-neocortical brain regions suggested that RA may have a separate, cell-autonomous function in brain endothelial cells to inhibit WNT signaling. Using both gain and loss of RA signaling approaches, we show that RA signaling in brain endothelial cells can inhibit WNT-β-catenin transcriptional activity and that this is required to moderate the expression of WNT target Sox17. From this, a model emerges in which RA acts upstream of the WNT pathway via non-cell-autonomous and cell-autonomous mechanisms to ensure the formation of an adequate and stable brain vascular plexus. SIGNIFICANCE STATEMENT Work presented here provides novel insight into important yet little understood aspects of brain vascular development, implicating for the first time a factor upstream of endothelial WNT signaling. We show that RA is permissive for cerebrovascular growth via

  15. Placebo Sleep Affects Cognitive Functioning

    ERIC Educational Resources Information Center

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  16. Macrophages form functional vascular mimicry channels in vivo

    PubMed Central

    Barnett, Faith H.; Rosenfeld, Mauricio; Wood, Malcolm; Kiosses, William B.; Usui, Yoshihiko; Marchetti, Valentina; Aguilar, Edith; Friedlander, Martin

    2016-01-01

    Macrophages, key cells of the innate immune system, are known to support angiogenesis but are not believed to directly form vessel walls. Here we show that macrophages structurally form primitive, NON-ENDOTHELIAL “vessels” or vascular mimicry (VM) channels in both tumor and angiogenesis in vivo models. These channels are functionally connected to the systemic vasculature as they are perfused by intravenously injected dye. Since both models share hypoxic micro-environments, we hypothesized that hypoxia may be an important mediator of VM formation. Indeed, conditional genetic depletion of myeloid-specific HIF-1α results in decreased VM network formation, dye perfusion and tumor size. Although the macrophage VM network shares some features with an endothelial vasculature, it is ultrastructurally different. Cancer stem cells have been shown to form vascular mimicry channels. Our data demonstrates that tumor-associated macrophages also form them. The identification of this novel type of vascular mimicry may help in the development of targeted cancer therapeutics. PMID:27834402

  17. Subclinical hypothyroidism affects mitochondrial function.

    PubMed

    Kvetny, J; Wilms, L; Pedersen, P L; Larsen, J

    2010-05-01

    The aim of the present study was to examine mitochondrial function in cells from persons with subclinical hypothyroidism and euthyroid controls. The participating persons were examined clinically and had basal oxygen consumption (VO(2)) determined. The concentrations of thyroid hormones and thyrotropine stimulating hormone were determined, and mitochondrial function in isolated mononuclear blood cells was examined by enzymatic methods [citrate synthase activity (CS)] and by flow cytometry (mitochondrial membrane potential by TMRM fluorescence and mitochondrial mass by MTG fluorescence). The ratio of T(4)/T(3) was lowered in subclinical hypothyroidism patients compared to controls (2.5+/-0.5 vs. 2.9+/-0.4, p=0.005). VO(2) was increased in persons with subclinical hypothyroidism compared to controls (adolescents: 134+/-27 ml O(2)/min*m(2) vs. 119+/-27 ml O(2)/min*m(2), p=0.006, adults: 139+/-14 ml O(2)/min*m(2) vs. 121+/-17 ml O(2)/min*m(2), p=0.001). The mitochondrial function, represented by citrate synthase activity, MTG, and TMRM fluorescence were all increased (CS in subclinical hypothyroidism vs. controls: 0.074+/-0.044 nmol/mg*min vs. 0.056+/-0.021 nmol/mg*min, p=0.005; MTG fluorescence in subclinical hypothyroidism vs. controls: 7,482+/-1,733 a.u. vs. 6,391+/-2,171 a.u., p=0.027; TMRM fluorescence in subclinical hypothyroidism vs. controls: 13,449+/-3,807 a.u. vs. 11,733+/-4,473 a.u, p=0.04). Our results indicate an increased mitochondrial stimulation, eventually caused by increased deiodination of T(4) to intracellular bioactive iodothyronines in adults and adolescents with subclinical hypothyroidism.

  18. Sympathetic regulation of vascular function in health and disease

    PubMed Central

    Bruno, Rosa M.; Ghiadoni, Lorenzo; Seravalle, Gino; Dell'Oro, Raffaella; Taddei, Stefano; Grassi, Guido

    2012-01-01

    The sympathetic nervous system (SNS) is known to play a pivotal role in short- and long-term regulation of different functions of the cardiovascular system. In the past decades increasing evidence demonstrated that sympathetic neural control is involved not only in the vasomotor control of small resistance arteries but also in modulation of large artery function. Sympathetic activity and vascular function, both of which are key factors in the development and prognosis of cardiovascular events and disease, are linked at several levels. Evidence from experimental studies indicates that the SNS is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, such as nitric oxide (NO), reactive oxygen species (ROS), endothelin (ET), the renin-angiotensin system. Additionally, there is indirect evidence of a reciprocal relationship between endothelial function and activity of the SNS. A number of cardiovascular risk factors and diseases are characterized both by increased sympathetic outflow and decreased endothelial function. In healthy subjects, muscle sympathetic nerve activity (MSNA) appears to be related to surrogate markers of endothelial function, and an acute increase in sympathetic activity has been associated with a decrease in endothelial function in healthy subjects. However, direct evidence of a cause-effect relationship from human studies is scanty. In humans large artery stiffness has been associated with increased sympathetic discharge, both in healthy subjects and in renal transplant recipients. Peripheral sympathetic discharge is also able to modulate wave reflection. On the other hand, large artery stiffness can interfere with autonomic regulation by impairing carotid baroreflex sensitivity. PMID:22934037

  19. Maternal Copper Deficiency Perpetuates Altered Vascular Function in Sprague-Dawley Rat Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known about the consequences of maternal Cu (Cu) deficiency on the vascular function of offspring or on perpetuation of vascular effects to a second generation. We examined vascular functional responses in mesenteric arteries from Cu-deficient Sprague-Dawley rat dams and from offspring dir...

  20. Assessment of vascular autonomic function using peripheral arterial tonometry.

    PubMed

    Hamada, Satomi; Oono, Ai; Ishihara, Yuri; Hasegawa, Yuki; Akaza, Miho; Sumi, Yuki; Inoue, Yoshinori; Izumiyama, Hajime; Hirao, Kenzo; Isobe, Mitsuaki; Sasano, Tetsuo

    2017-03-01

    Peripheral autonomic function is impaired in diabetic polyneuropathy. However, it is difficult to evaluate it due to the lack of non-invasive quantitative assessment. We aimed to establish a novel index to evaluate vascular autonomic function using reactive hyperemia peripheral arterial tonometry (RH-PAT), a widely performed endothelial function test. Sixty-five subjects were enrolled, including healthy subjects, cases with sympathetic nerve blockers, and diabetic patients. RH-PAT was performed with 5-min blood flow occlusion in unilateral arm. We calculated the reduction ratio of the post-occlusion pulse amplitude to the baseline in the non-occluded arm (RPN), with 1-min sliding window. In healthy subjects, RPN gradually increased with time-dependent manner. However, this phenomenon was eliminated in cases with sympathetic nerve blockers. Plasma concentration of norepinephrine was measured before and after the blood flow occlusion, which showed a significant increase. We then compared RPNs with the change in heart rate variability (HRV) parameters. RPN calculated at 5 min after the reperfusion had the highest correlation with the change in sympathetic HRV parameter, and thus, we named sympathetic hypoemia index (SHI). Finally, we studied the relationship between SHI and diabetes. SHI was significantly lower in diabetic patients than matched controls. SHI, a novel index derived from RH-PAT, represented the peripheral sympathetic activity. SHI may be useful for assessing the vascular autonomic activity in diabetic patients.

  1. Vascular function and brain-derived neurotrophic factor: The functional capacity factor.

    PubMed

    Alomari, Mahmoud A; Khabour, Omar F; Maikano, Abubakar; Alawneh, Khaldoon

    2015-12-01

    Brain-derived neurotrophic factor (BDNF) is essential for neurocognitive function. This study aims at establishing a plausible link between level of serum BDNF, functional capacity (FC), and vascular function in 181 young (age 25.5±9.1 years old), apparently healthy adults. Fasting blood samples were drawn from participants' antecubital veins into plain glass tubes while they were in a sitting position to evaluate serum BDNF using enzyme-linked immunosorbent assay (ELISA). Mercury-in-silastic strain-gauge plethysmography was used to determine arterial function indices, blood flow and vascular resistance at rest and following 5 minutes of arterial ischemia. The 6-minute walk distance (6MWD) test was used to determine FC, according to the American Thoracic Society Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories guidelines. It was conducted in an enclosed corridor on a flat surface with a circular track 33 meters long. The walking course was demarcated with bright colored cones. The 6MWD correlated with BDNF (r=0.3, p=0.000), as well as with forearm blood inflow (r=0.5, p=0.000) and vascular resistance (r = -0.4, p=0.000). Subsequent comparison showed that BDNF and blood inflow were greater (p<0.05) while vascular resistance was less (p<0.05) in participants who achieved a longer 6MWD. Similarly, BDNF correlated with forearm blood inflow (r=0.4, p=0.000) and vascular resistance (r = -0.4, p=0.000). Subsequent comparison showed improved vascular function (p<0.05) in the participants with greater BDNF. In conclusion, these findings might suggest that improved vascular function in individuals with greater FC is mediated, at least partially, by an enhanced serum BDNF level.

  2. Biomarkers of vascular function in premenopausal and recent postmenopausal women of similar age: effect of exercise training.

    PubMed

    Nyberg, Michael; Seidelin, Kaare; Andersen, Thomas Rostgaard; Overby, Nickie Neumann; Hellsten, Ylva; Bangsbo, Jens

    2014-04-01

    Menopause is associated with an accelerated decline in vascular function; however, whether this is an effect of age and/or menopause and how exercise training may affect this decline remains unclear. We examined a range of molecular measures related to vascular function in matched premenopausal and postmenopausal women before and after 12 wk of exercise training. Thirteen premenopausal and 10 recently postmenopausal [1.6 ± 0.3 (means ± SE) years after final menstrual period] women only separated by 3 yr (48 ± 1 vs. 51 ± 1 yr) were included. Before training, diastolic blood pressure, soluble intercellular adhesion molecule-1 (sICAM-1), and skeletal muscle expression of thromboxane A synthase were higher in the postmenopausal women compared with the premenopausal women, all indicative of impaired vascular function. In both groups, exercise training lowered diastolic blood pressure, the levels of sICAM-1, soluble vascular adhesion molecule-1 (sVCAM-1), as well as plasma and skeletal muscle endothelin-1. The vasodilator prostacyclin tended (P = 0.061) to be higher in plasma with training in the postmenopausal women only. These findings demonstrate that already within the first years after menopause, several biomarkers of vascular function are adversely altered, indicating that these biomarker changes are more related to hormonal changes than aging. Exercise training appears to have a positive impact on vascular function, as indicated by a marked improvement in the biomarker profile, in both premenopausal and postmenopausal women.

  3. Pulmonary vascular function in insulin resistance and diabetes.

    PubMed

    Moral-Sanz, Javier; Moreno, Laura; Cogolludo, Angel; Perez-Vizcaino, Francisco

    2014-05-01

    Insulin resistance and diabetes are current clinical concerns due to their increasing prevalence in western societies and in developing countries. Cardiovascular alterations, affecting both macro- and microcirculation, are among the major causes of illness and premature death within patients with insulin resistance or diabetes. However, the detrimental effects of insulin resistance and diabetes in the lungs are less clinically apparent, or at least masked by the progression of these metabolic diseases on other target organs. Epidemiological and experimental data suggest a link between pulmonary arterial hypertension and diabetes. Thereby, hemodynamic derangements in uncontrolled diabetes or insulin resistance are predisposing factors leading to early pulmonary alterations that in association with a second hit might accelerate the onset of pulmonary vascular disease and pulmonary hypertension. The present article reviewed the current knowledge about the effects of insulin resistance and diabetes in a territory which has received little attention until recently: the pulmonary circulation.

  4. Subchronic arsenic exposure through drinking water alters vascular redox homeostasis and affects physical health in rats.

    PubMed

    Waghe, Prashantkumar; Sarath, Thengumpallil Sasindran; Gupta, Priyanka; Kutty, Harikumar Sankaran; Kandasamy, Kannan; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-12-01

    We evaluated whether arsenic can alter vascular redox homeostasis and modulate antioxidant status, taking rat thoracic aorta as a model vascular tissue. In addition, we evaluated whether the altered vascular biochemical homeostasis could be associated with alterations in the physical indicators of toxicity development. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. Body weight, food intake, and water consumption were recorded weekly. On the 91st day, rats were sacrificed; vital organs and thoracic aorta were collected. Lipid peroxidation, reactive oxygen species generation, and antioxidants were assessed in the thoracic aorta. Arsenic increased aortic lipid peroxidation and hydrogen peroxide generation while decreased reduced glutathione content in a dose-dependent manner. The activities of the enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were decreased. Further, arsenic at 100 ppm decreased feed intake, water consumption, and body weight from the 11th week onward. At this concentration, arsenic increased the relative weights of the liver and kidney. The results suggest that arsenic causes dose-dependent oxidative stress, reduction in antioxidative defense systems, and body weight loss with alteration in hepato-renal organosomatic indices. Overall, subchronic arsenic exposure through drinking water causes alteration in vascular redox homeostasis and at high concentration affects physical health.

  5. Regulation of Vascular and Renal Function by Metabolite Receptors*

    PubMed Central

    Peti-Peterdi, János; Kishore, Bellamkonda K.; Pluznick, Jennifer L.

    2016-01-01

    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis—from salt and water balance to metabolism—by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families—(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and (c) short-chain fatty acid receptors—we emphasize the unique and important roles that these receptors play in renal and vascular physiology and pathophysiology. PMID:26667077

  6. The KEEPS-Cognitive and Affective Study: Baseline Associations between Vascular Risk Factors and Cognition

    PubMed Central

    Wharton, Whitney; Gleason, Carey E.; Dowling, N. Maritza; Carlsson, Cynthia M.; Brinton, Eliot A.; Santoro, M. Nanette; Neal-Perry, Genevieve; Taylor, Hugh; Naftolin, Frederick; Lobo, Rogerio; Merriam, George; Manson, JoAnn E.; Cedars, Marcelle; Miller, Virginia M.; Black, Dennis M.; Budoff, Matthew; Hodis, Howard N.; Harman, Mitchell; Asthana, Sanjay

    2015-01-01

    Background Midlife vascular risk factors influence later cognitive decline and Alzheimer’s disease (AD). The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk, such as high blood pressure (BP), which independently contribute to cognitive dysfunction and AD. Methods We describe the extent to which vascular risk factors relate to cognition in healthy, middle–aged, recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS-Cog) at baseline. KEEPS-Cog is a double-blind, randomized, placebo-controlled, parallel group design, clinical trial, investigating the efficacy of low-dose, transdermal 17β-estradiol and oral conjugated equine estrogen on cognition. Results The KEEPS-Cog cohort (N=662) is healthy and free of cognitive dysfunction. Higher systolic BP was related to poorer performance in auditory working memory and attention (unadjusted p=0.004; adjusted p=0.10). This relationship was not associated with endogenous hormone levels. Conclusions Lower BP early in menopause may positively affect cognitive domains known to be associated with AD. PMID:24430001

  7. Flosequinan does not affect systemic and regional vascular responses to simulated orthostatic stress in healthy volunteers.

    PubMed Central

    Duranteau, J; Pussard, E; Edouard, A; Samii, K; Berdeaux, A; Giudicelli, J F

    1992-01-01

    1. The effects of a single oral dose (100 mg) of flosequinan on systemic and regional (forearm, splanchnic and renal) vascular responses to simulated orthostatic stress (lower body negative pressure, LBNP) were investigated in nine healthy male volunteers, in a double-blind, placebo-controlled crossover study. 2. Forty-five minutes after its administration and before LBNP, flosequinan induced a significant decrease in total peripheral and in forearm vascular resistances without any concomitant change in arterial pressure, in heart rate and in the investigated biological parameters (plasma catecholamines, arginine vasopressin and renin activity). 3. After flosequinan and placebo, LBNP induced similar decreases in central venous pressure at all levels of LBNP (-10, -20 and -40 mm Hg) and in pulse pressure at LBNP -40 mm Hg. LBNP-induced increase in forearm vascular resistance was significantly more marked after flosequinan than after placebo at all levels of LBNP, and this was also true for splanchnic vascular resistance but at LBNP -40 mm Hg only. However, inasmuch as the basal values of these two parameters before LBNP were lower after flosequinan than after placebo, their final values after LBNP -40 mm Hg were similar. Finally, LBNP-induced changes in renal vascular resistance, glomerular filtration rate and filtration fraction as well as in plasma catecholamines, arginine vasopressin and renin activity were similar after flosequinan and placebo at all levels of LBNP. 4. Flosequinan affected neither reflex control of heart rate (phenylephrine test) nor non-specific vasoconstrictor responses (cold pressor test). (ABSTRACT TRUNCATED AT 250 WORDS) PMID:1389945

  8. Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells.

    PubMed

    Rellick, Stephanie L; Hu, Heng; Simpkins, James W; Ren, Xuefang

    2016-11-19

    The integrity of the blood-brain-barrier (BBB) is critical to prevent brain injury. Cerebral vascular endothelial (CVE) cells are one of the cell types that comprise the BBB; these cells have a very high-energy demand, which requires optimal mitochondrial function. In the case of disease or injury, the mitochondrial function in these cells can be altered, resulting in disease or the opening of the BBB. In this manuscript, we introduce a method to measure mitochondrial function in CVE cells by using whole, intact cells and a bioanalyzer. A mito-stress assay is used to challenge the cells that have been perturbed, either physically or chemically, and evaluate their bioenergetic function. Additionally, this method also provides a useful way to screen new therapeutics that have direct effects on mitochondrial function. We have optimized the cell density necessary to yield oxygen consumption rates that allow for the calculation of a variety of mitochondrial parameters, including ATP production, maximal respiration, and spare capacity. We also show the sensitivity of the assay by demonstrating that the introduction of the microRNA, miR-34a, leads to a pronounced and detectable decrease in mitochondrial activity. While the data shown in this paper is optimized for the bEnd.3 cell line, we have also optimized the protocol for primary CVE cells, further suggesting the utility in preclinical and clinical models.

  9. Blood flow controls bone vascular function and osteogenesis

    PubMed Central

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Schiller, Maria; Zeuschner, Dagmar; Bixel, M. Gabriele; Milia, Carlo; Gamrekelashvili, Jaba; Limbourg, Anne; Medvinsky, Alexander; Santoro, Massimo M.; Limbourg, Florian P.; Adams, Ralf H.

    2016-01-01

    While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system. PMID:27922003

  10. Stress hormones and vascular function in firefighters during concurrent challenges.

    PubMed

    Webb, Heather E; Garten, Ryan S; McMinn, David R; Beckman, Jamie L; Kamimori, Gary H; Acevedo, Edmund O

    2011-04-01

    The purpose of this study was to examine the effects of concurrent physical and mental challenge on stress hormones and indicators of vascular function in firefighters. Twelve professional firefighters exercised at 60% VO(2max) while participating in a computerized Fire Strategies and Tactics Drill (FSTD-fire strategies condition [FSC]), and again at the same intensity without the mental challenge (EAC). No differences in the amount of work performed between conditions existed, although the FSC resulted in greater perceptions of overall workload. Epinephrine and norepinephrine demonstrated significant interaction effects with elevated levels during the FSC. Cortisol responses were significantly elevated across time and for the FSC. Positive correlations were found between cortisol and interleukin-6, endothelin-1, and thromboxane-B(2), and a negative correlation between interleukin-6 and thromboxane-B(2). These results suggest that concurrent challenges results in exacerbated responses of stress hormones and suggests mechanisms that could contribute to the prevalence of cardiovascular events among firefighters.

  11. The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development

    PubMed Central

    Fourquin, Chloé; Primo, Amparo; Martínez-Fernández, Irene; Huet-Trujillo, Estefanía; Ferrándiz, Cristina

    2014-01-01

    Background and Aims CRABS CLAW (CRC) is a member of the YABBY family of transcription factors involved in carpel morphogenesis, floral determinacy and nectary specification in arabidopsis. CRC orthologues have been functionally characterized across angiosperms, revealing additional roles in leaf vascular development and carpel identity specification in Poaceae. These studies support an ancestral role of CRC orthologues in carpel development, while roles in vascular development and nectary specification appear to be derived. This study aimed to expand research on CRC functional conservation to the legume family in order to better understand the evolutionary history of CRC orthologues in angiosperms. Methods CRC orthologues from Pisum sativum and Medicago truncatula were identified. RNA in situ hybridization experiments determined the corresponding expression patterns throughout flower development. The phenotypic effects of reduced CRC activity were investigated in P. sativum using virus-induced gene silencing. Key Results CRC orthologues from P. sativum and M. truncatula showed similar expression patterns, mainly restricted to carpels and nectaries. However, these expression patterns differed from those of other core eudicots, most importantly in a lack of abaxial expression in the carpel and in atypical expression associated with the medial vein of the ovary. CRC downregulation in pea caused defects in carpel fusion and style/stigma development, both typically associated with CRC function in eudicots, but also affected vascular development in the carpel. Conclusions The data support the conserved roles of CRC orthologues in carpel fusion, style/stigma development and nectary development. In addition, an intriguing new aspect of CRC function in legumes was the unexpected role in vascular development, which could be shared by other species from widely diverged clades within the angiosperms, suggesting that this role could be ancestral rather than derived, as so far

  12. Cybersickness provoked by head-mounted display affects cutaneous vascular tone, heart rate and reaction time.

    PubMed

    Nalivaiko, Eugene; Davis, Simon L; Blackmore, Karen L; Vakulin, Andrew; Nesbitt, Keith V

    2015-11-01

    Evidence from studies of provocative motion indicates that motion sickness is tightly linked to the disturbances of thermoregulation. The major aim of the current study was to determine whether provocative visual stimuli (immersion into the virtual reality simulating rides on a rollercoaster) affect skin temperature that reflects thermoregulatory cutaneous responses, and to test whether such stimuli alter cognitive functions. In 26 healthy young volunteers wearing head-mounted display (Oculus Rift), simulated rides consistently provoked vection and nausea, with a significant difference between the two versions of simulation software (Parrot Coaster and Helix). Basal finger temperature had bimodal distribution, with low-temperature group (n=8) having values of 23-29 °C, and high-temperature group (n=18) having values of 32-36 °C. Effects of cybersickness on finger temperature depended on the basal level of this variable: in subjects from former group it raised by 3-4 °C, while in most subjects from the latter group it either did not change or transiently reduced by 1.5-2 °C. There was no correlation between the magnitude of changes in the finger temperature and nausea score at the end of simulated ride. Provocative visual stimulation caused prolongation of simple reaction time by 20-50 ms; this increase closely correlated with the subjective rating of nausea. Lastly, in subjects who experienced pronounced nausea, heart rate was elevated. We conclude that cybersickness is associated with changes in cutaneous thermoregulatory vascular tone; this further supports the idea of a tight link between motion sickness and thermoregulation. Cybersickness-induced prolongation of reaction time raises obvious concerns regarding the safety of this technology.

  13. Degree of bioresorbable vascular scaffold expansion modulates loss of essential function

    PubMed Central

    Ferdous, Jahid; Kolachalama, Vijaya B.; Kolandaivelu, Kumaran; Shazly, Tarek

    2015-01-01

    Drug-eluting bioresorbable vascular scaffolds (BVSs) have the potential to restore lumen patency, enable recovery of the native vascular environment, and circumvent late complications associated with permanent endovascular devices. To ensure therapeutic effects persist for sufficient times prior to scaffold resorption and resultant functional loss, many factors dictating BVS performance must be identified, characterized and optimized. While some factors relate to BVS design and manufacturing, others depend on device deployment and intrinsic vascular properties. Importantly, these factors interact and cannot be considered in isolation. The objective of this study is to quantify the extent to which degree of radial expansion modulates BVS performance, specifically in the context of modifying device erosion kinetics and evolution of structural mechanics and local drug elution. We systematically varied degree of radial expansion in model BVS constructs composed of poly DL-lactide-glycolide and generated in-vitro metrics of device microstructure, degradation, erosion, mechanics and drug release. Experimental data permitted development of computational models that predicted transient concentrations of scaffold-derived soluble species and drug in the arterial wall, thus enabling speculation on the short- and long-term effects of differential expansion. We demonstrate degree of expansion significantly affects scaffold properties critical to functionality, underscoring its relevance in BVS design and optimization. PMID:26277377

  14. Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis

    PubMed Central

    2016-01-01

    Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients. PMID:26955238

  15. Enhanced functions of vascular cells on nanostructured Ti for improved stent applications.

    PubMed

    Choudhary, Saba; Haberstroh, Karen M; Webster, Thomas J

    2007-07-01

    Vascular tissue possesses numerous nanostructured surface features, but most metallic vascular stents proposed to restore blood flow are smooth at the nanoscale. Thus, the objective of the present study was to determine in vitro vascular cell functions on nanostructured titanium (Ti) compared to conventional commercially pure (c.p.) Ti. Results of this study showed for the first time greater competitive adhesion of endothelial versus vascular smooth muscle cells on nanostructured Ti compared to conventional Ti after 4 hours. Moreover, when cultured separately, increased endothelial and vascular smooth muscle cell density was observed on nanostructured Ti compared to conventional c.p. Ti after 1, 3, and 5 days; endothelial cells formed confluent monolayers before vascular smooth muscle cells on nanostructured Ti. Results also showed greater total amounts of collagen and elastin synthesis by vascular cells when cultured on nanostructured Ti. Since a major mode of failure of conventional vascular stents is the overgrowth of smooth muscle cells compared to endothelial cells, these results suggest that while the functions of both types of vascular cells were promoted on nanostructured c.p. Ti, endothelial cell functions (of particular importance, cell density or confluence) were enhanced over that of vascular smooth muscle cells. Thus, the present in vitro study showed that vascular stents composed of nanometer c.p. Ti particles may invoke advantageous cellular responses for improved stent applications.

  16. Pulmonary vascular function and exercise capacity in black sub-Saharan Africans.

    PubMed

    Simaga, Bamodi; Vicenzi, Marco; Faoro, Vitalie; Caravita, Sergio; Di Marco, Giovanni; Forton, Kevin; Deboeck, Gael; Lalande, Sophie; Naeije, Robert

    2015-09-01

    Sex and age affect the pulmonary circulation. Whether there may be racial differences in pulmonary vascular function is unknown. Thirty white European Caucasian subjects (15 women) and age and body-size matched 30 black sub-Saharan African subjects (15 women) underwent a cardiopulmonary exercise test and exercise stress echocardiography with measurements of pulmonary artery pressure (PAP) and cardiac output (CO). A pulmonary vascular distensibility coefficient α was mathematically determined from the natural curvilinearity of multipoint mean PAP (mPAP)-CO plots. Maximum oxygen uptake (V̇o2max) and workload were higher in the whites, while maximum respiratory exchange ratio and ventilatory equivalents for CO2 were the same. Pulmonary hemodynamics were not different at rest. Exercise was associated with a higher maximum total pulmonary vascular resistance, steeper mPAP-CO relationships, and lower α-coefficients in the blacks. These differences were entirely driven by higher slopes of mPAP-CO relationships (2.5 ± 0.7 vs. 1.4 ± 0.7 mmHg·l(-1)·min; P < 0.001) and lower α-coefficients (0.85 ± 0.33 vs. 1.35 ± 0.51%/mmHg; P < 0.01) in black men compared with white men. There were no differences in any of the hemodynamic variables between black and white women. In men only, the slopes of mPAP-CO relationships were inversely correlated to V̇o2max (P < 0.01). Thus the pulmonary circulation is intrinsically less distensible in black sub-Saharan African men compared with white Caucasian Europeans men, and this is associated with a lower exercise capacity. This study did not identify racial differences in pulmonary vascular function in women.

  17. Regulation of Vascular and Renal Function by Metabolite Receptors.

    PubMed

    Peti-Peterdi, János; Kishore, Bellamkonda K; Pluznick, Jennifer L

    2016-01-01

    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis-from salt and water balance to metabolism-by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families-(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and

  18. Functional CB1 cannabinoid receptors in human vascular endothelial cells.

    PubMed Central

    Liu, J; Gao, B; Mirshahi, F; Sanyal, A J; Khanolkar, A D; Makriyannis, A; Kunos, G

    2000-01-01

    Cannabinoid CB1 receptor mRNA was detected using reverse transcription-polymerase chain reaction (RT-PCR) in endothelial cells from human aorta and hepatic artery and in the ECV304 cell line derived from human umbilical vein endothelial cells. CB1 receptor-binding sites were detected by the high-affinity antagonist radioligand [(125)I]AM-251. In ECV304 cells, both the highly potent synthetic cannabinoid agonist HU-210 and the endogenous ligand anandamide induce activation of mitogen-activated protein (MAP) kinase, and the effect of HU-210 was completely blocked, whereas the effect of anandamide was partially inhibited by SR141716A, a selective CB1 receptor antagonist. Transfection of ECV304 cells with CB1 receptor antisense, but not sense, oligonucleotides caused the same pattern of inhibition as SR141716A. This provides more definitive evidence for the involvement of CB1 receptors in MAP kinase activation and suggests that anandamide may also activate MAP kinase via an additional, CB1 receptor-independent, SR141716A-resistant mechanism. The MAP kinase activation by anandamide in ECV304 cells requires genistein-sensitive tyrosine kinases and protein kinase C (PKC), and anandamide also activates p38 kinase and c-Jun kinase. These findings indicate that CB1 receptors located in human vascular endothelium are functionally coupled to the MAP kinase cascade. Activation of protein kinase cascades by anandamide may be involved in the modulation of endothelial cell growth and proliferation. PMID:10698714

  19. Direct Effects of Phosphate on Vascular Cell Function

    PubMed Central

    Lau, Wei Ling; Pai, Ashwini; Moe, Sharon M.; Giachelli, Cecilia M.

    2011-01-01

    Elevated serum phosphate has clinically been associated with vascular stiffness and cardiovascular mortality. Mechanistic studies over the past decade looking at phosphate’s local effects on the vessel wall have lent insight into various pathways that culminate in vascular calcification.Smooth muscle cell phenotype change and apoptosis play prominent roles. The sodium-phosphate cotransporter PiT-1 is required for the osteochondrogenic differentiation of smooth muscle cellsin vitro. Less is known about phosphate-driven valve interstitial cell calcification and elastin degradation.In this paper, we review the current knowledge about phosphate-induced changes in the vascular wall. PMID:21406295

  20. Effects of successive air and nitrox dives on human vascular function.

    PubMed

    Marinovic, Jasna; Ljubkovic, Marko; Breskovic, Toni; Gunjaca, Grgo; Obad, Ante; Modun, Darko; Bilopavlovic, Nada; Tsikas, Dimitrios; Dujic, Zeljko

    2012-06-01

    SCUBA diving is regularly associated with asymptomatic changes in cardiac, pulmonary and vascular function. The aim of this study was to evaluate the changes in vascular/endothelial function following SCUBA diving and to assess the potential difference between two breathing gases: air and nitrox 36 (36% oxygen and 64% nitrogen). Ten divers performed two 3-day diving series (no-decompression dive to 18 m with 47 min bottom time with air and nitrox, respectively), with 2 weeks pause in between. Arterial/endothelial function was assessed using SphygmoCor and flow-mediated dilation measurements, and concentration of nitrite before and after diving was determined in venous blood. Production of nitrogen bubbles post-dive was assessed by ultrasonic determination of venous gas bubble grade. Significantly higher bubbling was found after all air dives as compared to nitrox dives. Pulse wave velocity increased slightly (~6%), significantly after both air and nitrox diving, indicating an increase in arterial stiffness. However, augmentation index became significantly more negative after diving indicating smaller wave reflection. There was a trend for post-dive reduction of FMD after air dives; however, only nitrox diving significantly reduced FMD. No significant differences in blood nitrite before and after the dives were found. We found that nitrox diving affects systemic/vascular function more profoundly than air diving by reducing FMD response, most likely due to higher oxygen load. Both air and nitrox dives increased arterial stiffness, but decreased wave reflection suggesting a decrease in peripheral resistance due to exercise during diving. These effects of nitrox and air diving were not followed by changes in plasma nitrite.

  1. Evidence of species specific vascular plant functions as regulators of methane emissions from northern peatlands

    NASA Astrophysics Data System (ADS)

    Oquist, M. G.

    2001-05-01

    Peatlands play an indisputable role in the global carbon cycle by their net accumulation of atmospheric carbon dioxide and storage of carbon in the form of peat. They are also intimately tied into the fundamental processes of the atmospheric greenhouse gas balance through their production and concomitant emission of methane. During the last decade several studies have emphasized the function of vegetation as an important regulator of methane emissions from wetland ecosystems, including northern peatlands. Vascular plants can affect methane emissions either by facilitating transportation of methane over the soil/atmosphere interface, or by supplying the microbial soil communities with readily degradable organic substrates through root activity, stimulating biogeochemical transformation rates including methanogenesis. We found evidence of both these types of vegetation-based interactions in a sub-arctic peatland ecosystem and also indications that the two different processes of vegetation induced stimulation of methane emission rates are species specific with respect to the vascular plant communities. By reducing incoming PAR through shading manipulations and comparing these to ambient light control plots we created an intra-habitat gradient of vascular plant photosynthesis at two contrasting sites, one ombrotrophic (dominated by Eriophorum vaginatum/Carex rotundata) and one minerotrophic (dominated by Eriophorum angustifolium). The position of the water table was found to be the dominating environmental factor controlling methane emission rates in both habitat types. At the ombrotrophic site the photosynthetic rate was the second most important factor, especially during peak vascular plant activity (late June- early August) when this variable could explain ca 15% of the variations in methane flux rates. Furthermore, the photosynthetic rates in the shaded plots were reduced by ca 25% and was accompanied by a significant 20% (P=0.01) reduction in methane emission

  2. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits.

    PubMed

    Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

    2015-01-01

    Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis.

  3. Severe vascular complications in patients affected by systemic sclerosis cyclically treated with iloprost.

    PubMed

    Caramaschi, Paola; Dalla Gassa, Alessandra; Prati, Daniele; Barausse, Giovanni; Tinazzi, Ilaria; Ravagnani, Viviana; Confente, Silvia; Biasi, Domenico

    2012-07-01

    The objective of this study was to evaluate the incidence of the most severe vascular complications, such as pulmonary arterial hypertension, scleroderma renal crisis, and digital necrosis requiring amputation, in a monocentric group of systemic sclerosis (SSc) patients cyclically treated with intravenous iloprost. We reviewed the record-charts of 115 patients affected by SSc (18 men and 97 women, mean age 58.9.1 ± 14.2 years) regularly receiving iloprost for at least 3 years; the mean duration of the treatment was 98.8 ± 37.5 months (a total of 946.8 years of therapy). Demographic and clinical features were recorded. None of the patients died of SSc-associated vascular complications. After iloprost administration digital gangrene requiring amputation developed in 2 patients who had concomitant peripheral arterial disease (a total of 3 episodes; annual incidence of 0.31 for 100 years of iloprost therapy). Four patients were diagnosed with pulmonary arterial hypertension during iloprost treatment (annual incidence of 0.42 for 100 years of drug therapy); in none of the cases did the complication show a progressive course. No cases of scleroderma renal crisis were observed. With the limits of an observational study and in the absence of a control group, our experience suggests that prolonged cyclic iloprost therapy may limit the incidence/progression of severe digital and visceral SSc-vasculopathy.

  4. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits

    PubMed Central

    Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

    2015-01-01

    Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis. PMID:26175757

  5. Vascular Endothelial Growth Factor Modulates Skeletal Myoblast Function

    PubMed Central

    Germani, Antonia; Di Carlo, Anna; Mangoni, Antonella; Straino, Stefania; Giacinti, Cristina; Turrini, Paolo; Biglioli, Paolo; Capogrossi, Maurizio C.

    2003-01-01

    Vascular endothelial growth factor (VEGF) expression is enhanced in ischemic skeletal muscle and is thought to play a key role in the angiogenic response to ischemia. However, it is still unknown whether, in addition to new blood vessel growth, VEGF modulates skeletal muscle cell function. In the present study immunohistochemical analysis showed that, in normoperfused mouse hindlimb, VEGF and its receptors Flk-1 and Flt-1 were expressed mostly in quiescent satellite cells. Unilateral hindlimb ischemia was induced by left femoral artery ligation. At day 3 and day 7 after the induction of ischemia, Flk-1 and Flt-1 were expressed in regenerating muscle fibers and VEGF expression by these fibers was markedly enhanced. Additional in vitro experiments showed that in growing medium both cultured satellite cells and myoblast cell line C2C12 expressed VEGF and its receptors. Under these conditions, Flk-1 receptor exhibited constitutive tyrosine phosphorylation that was increased by VEGF treatment. During myogenic differentiation Flk-1 and Flt-1 were down-regulated. In a modified Boyden Chamber assay, VEGF enhanced C2C12 myoblasts migration approximately fivefold. Moreover, VEGF administration to differentiating C2C12 myoblasts prevented apoptosis, while inhibition of VEGF signaling either with selective VEGF receptor inhibitors (SU1498 and CB676475) or a neutralizing Flk-1 antibody, enhanced cell death approximately 3.5-fold. Finally, adenovirus-mediated VEGF165 gene transfer inhibited ischemia-induced apoptosis in skeletal muscle. These results support a role for VEGF in myoblast migration and survival, and suggest a novel autocrine role of VEGF in skeletal muscle repair during ischemia. PMID:14507649

  6. Scaling laws of vascular trees: of form and function.

    PubMed

    Kassab, Ghassan S

    2006-02-01

    The branching pattern and vascular geometry of biological tree structure are complex. Here we show that the design of all vascular trees for which there exist morphometric data in the literature (e.g., coronary, pulmonary; vessels of various skeletal muscles, mesentery, omentum, and conjunctiva) obeys a set of scaling laws that are based on the hypothesis that the cost of construction of the tree structure and operation of fluid conduction is minimized. The laws consist of scaling relationships between 1) length and vascular volume of the tree, 2) lumen diameter and blood flow rate in each branch, and 3) diameter and length of vessel branches. The exponent of the diameter-flow rate relation is not necessarily equal to 3.0 as required by Murray's law but depends on the ratio of metabolic to viscous power dissipation of the tree of interest. The major significance of the present analysis is to show that the design of various vascular trees of different organs and species can be deduced on the basis of the minimum energy hypothesis and conservation of energy under steady-state conditions. The present study reveals the similarity of nature's scaling laws that dictate the design of various vascular trees and the underlying physical and physiological principles.

  7. Vascular permeability, vascular hyperpermeability and angiogenesis

    PubMed Central

    Nagy, Janice A.; Benjamin, Laura; Zeng, Huiyan; Dvorak, Ann M.

    2008-01-01

    The vascular system has the critical function of supplying tissues with nutrients and clearing waste products. To accomplish these goals, the vasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. Physiologists and many vascular biologists differ as to the definition of vascular permeability and the proper methodology for its measurement. We review these conflicting views, finding that both provide useful but complementary information. Vascular permeability by any measure is dramatically increased in acute and chronic inflammation, cancer, and wound healing. This hyperpermeability is mediated by acute or chronic exposure to vascular permeabilizing agents, particularly vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A). We demonstrate that three distinctly different types of vascular permeability can be distinguished, based on the different types of microvessels involved, the composition of the extravasate, and the anatomic pathways by which molecules of different size cross-vascular endothelium. These are the basal vascular permeability (BVP) of normal tissues, the acute vascular hyperpermeability (AVH) that occurs in response to a single, brief exposure to VEGF-A or other vascular permeabilizing agents, and the chronic vascular hyperpermeability (CVH) that characterizes pathological angiogenesis. Finally, we list the numerous (at least 25) gene products that different authors have found to affect vascular permeability in variously engineered mice and classify them with respect to their participation, as far as possible, in BVP, AVH and CVH. Further work will be required to elucidate the signaling pathways by which each of these molecules, and others likely to be discovered, mediate the different types of vascular permeability. PMID:18293091

  8. Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall

    PubMed Central

    Zanetti, Michela; Grillo, Andrea; Losurdo, Pasquale; Panizon, Emiliano; Mearelli, Filippo; Cattin, Luigi; Barazzoni, Rocco; Carretta, Renzo

    2015-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFA) consumption is associated with reduced cardiovascular disease risk. Increasing evidence demonstrating a beneficial effect of n-3 PUFA on arterial wall properties is progressively emerging. We reviewed the recent available evidence for the cardiovascular effects of n-3 PUFA focusing on structural and functional properties of the vascular wall. In experimental studies and clinical trials n-3 PUFA have shown the ability to improve arterial hemodynamics by reducing arterial stiffness, thus explaining some of its cardioprotective properties. Recent studies suggest beneficial effects of n-3 PUFA on endothelial activation, which are likely to improve vascular function. Several molecular, cellular, and physiological pathways influenced by n-3 PUFA can affect arterial wall properties and therefore interfere with the atherosclerotic process. Although the relative weight of different physiological and molecular mechanisms and the dose-response on arterial wall properties have yet to be determined, n-3 PUFA have the potential to beneficially impact arterial wall remodeling and cardiovascular outcomes by targeting arterial wall stiffening and endothelial dysfunction. PMID:26301252

  9. Endothelial PECAM-1 and its function in vascular physiology and atherogenic pathology.

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-06-01

    Platelet endothelial cell adhesion molecule (PECAM-1) is highly expressed in vascular cells such as endothelial cells (ECs) and blood-borne cells like platelets and leukocytes. In ECs, this molecule controls junctional and adhesive properties. In physiological conditions, PECAM-1 supports the endothelial barrier function. In inflammation that is observed in vessels affected by atherosclerosis, the function of PECAM-1 is impaired, an event that leads to increased adhesion of neutrophils and other leukocytes to ECs, decreased vascular integrity, and higher leukocyte transmigration to the intima media. PECAM-1 has six extracellular immunoglobulin (Ig)-like domains that support attraction and adhesion of leukocytes to ECs. The cytoplasmic tail of PECAM-1 contains two tyrosine residues (Tyr-663 and Tyr-686) that could be phosphorylated by Src family protein kinases is involved in the intracellular signaling. Actually, those tyrosines are the part of the immunoreceptor tyrosine-based inhibition motifs (ITIMs) that inhibit inflammation. However, in atherosclerosis, the PECAM-1-dependent immune suppression is disturbed. This in turn facilitates recruitment of leukocytes and supports proatherogenic inflammation.

  10. The plant vascular system: Evolution, development and functions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased stature, photosynthetic output, and ability to colonize a greatly expanded range of ...

  11. Non-patient related variables affecting levels of vascular endothelial growth factor in urine biospecimens.

    PubMed

    Kirk, M J; Hayward, R M; Sproull, M; Scott, T; Smith, S; Cooley-Zgela, T; Crouse, N S; Citrin, D E; Camphausen, K

    2008-08-01

    Vascular endothelial growth factor (VEGF) is an angiogenic protein proposed to be an important biomarker for the prediction of tumour growth and disease progression. Recent studies suggest that VEGF measurements in biospecimens, including urine, may have predictive value across a range of cancers. However, the reproducibility and reliability of urinary VEGF measurements have not been determined. We collected urine samples from patients receiving radiation treatment for glioblastoma multiforme (GBM) and examined the effects of five variables on measured VEGF levels using an ELISA assay. To quantify the factors affecting the precision of the assay, two variables were examined: the variation between ELISA kits with different lot numbers and the variation between different technicians. Three variables were tested for their effects on measured VEGF concentration: the time the specimen spent at room temperature prior to assay, the addition of protease inhibitors prior to specimen storage and the alteration of urinary pH. This study found that VEGF levels were consistent across three different ELISA kit lot numbers. However, significant variation was observed between results obtained by different technicians. VEGF concentrations were dependent on time at room temperature before measurement, with higher values observed 3-7 hrs after removal from the freezer. No significant difference was observed in VEGF levels with the addition of protease inhibitors, and alteration of urinary pH did not significantly affect VEGF measurements. In conclusion, this determination of the conditions necessary to reliably measure urinary VEGF levels will be useful for future studies related to protein biomarkers and disease progression.

  12. Tie1 controls angiopoietin function in vascular remodeling and inflammation

    PubMed Central

    Korhonen, Emilia A.; Lampinen, Anita; Giri, Hemant; Kim, Minah; Allen, Breanna; D’Amico, Gabriela; Sipilä, Tuomas J.; Lohela, Marja; Vaheri, Antti; Ylä-Herttuala, Seppo; Koh, Gou Young; McDonald, Donald M.

    2016-01-01

    The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, and vessel leakage. ANG1 is a Tie2 agonist that promotes vascular stabilization in inflammation and sepsis, whereas ANG2 is a context-dependent Tie2 agonist or antagonist. A limited understanding of ANG signaling mechanisms and the orphan receptor Tie1 has hindered development of ANG/Tie-targeted therapeutics. Here, we determined that both ANG1 and ANG2 binding to Tie2 increases Tie1-Tie2 interactions in a β1 integrin–dependent manner and that Tie1 regulates ANG-induced Tie2 trafficking in endothelial cells. Endothelial Tie1 was essential for the agonist activity of ANG1 and autocrine ANG2. Deletion of endothelial Tie1 in mice reduced Tie2 phosphorylation and downstream Akt activation, increased FOXO1 nuclear localization and transcriptional activation, and prevented ANG1- and ANG2-induced capillary-to-venous remodeling. However, in acute endotoxemia, the Tie1 ectodomain that is responsible for interaction with Tie2 was rapidly cleaved, ANG1 agonist activity was decreased, and autocrine ANG2 agonist activity was lost, which led to suppression of Tie2 signaling. Tie1 cleavage also occurred in patients with hantavirus infection. These results support a model in which Tie1 directly interacts with Tie2 to promote ANG-induced vascular responses under noninflammatory conditions, whereas in inflammation, Tie1 cleavage contributes to loss of ANG2 agonist activity and vascular stability. PMID:27548530

  13. Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men.

    PubMed

    Esser, Diederik; Mars, Monica; Oosterink, Els; Stalmach, Angelique; Müller, Michael; Afman, Lydia A

    2014-03-01

    Flavanol-enriched chocolate consumption increases endothelium-dependent vasodilation. Most research so far has focused on flow-mediated dilation (FMD) only; the effects on other factors relevant to endothelial health, such as inflammation and leukocyte adhesion, have hardly been addressed. We investigated whether consumption of regular dark chocolate also affects other markers of endothelial health, and whether chocolate enrichment with flavanols has additional benefits. In a randomized double-blind crossover study, the effects of acute and of 4 wk daily consumption of high flavanol chocolate (HFC) and normal flavanol chocolate (NFC) on FMD, augmentation index (AIX), leukocyte count, plasma cytokines, and leukocyte cell surface molecules in overweight men (age 45-70 yr) were investigated. Sensory profiles and motivation scores to eat chocolate were also collected. Findings showed that a 4 wk chocolate intake increased FMD by 1%, which was paralleled by a decreased AIX of 1%, decreased leukocyte cell count, decreased plasma sICAM1 and sICAM3, and decreased leukocyte adhesion marker expression (P<0.05 for time effect), with no difference between HFC and NFC consumption. Flavanol enrichment did affect taste and negatively affected motivation to consume chocolate. This study provides new insights on how chocolate affects endothelial health by demonstrating that chocolate consumption, besides improving vascular function, also lowers the adherence capacity of leukocytes in the circulation.

  14. The Primo Vascular Structures Alongside Nervous System: Its Discovery and Functional Limitation

    PubMed Central

    Park, Eun-sung; Kim, Hee Young; Youn, Dong-ho

    2013-01-01

    The primo vascular structures comprising primo nodes and vessels (originally called Bonghan corpuscles and ducts, resp.) have recently been suggested to be the anatomical correlate of acupuncture, a therapeutic technique used in oriental medicine. Although the primo vascular structures have been observed in many parts of animals, including the nervous system, using anatomical methodologies, its physiological functions are still unclear. This paper summarizes the reports on the primo vascular structures, particularly in the nervous system and its surroundings, as well as the electrophysiological properties of cells in the primo nodes. In addition, recent reports examining the potential roles of the primo vascular structures in acupuncture are discussed. This review raises some fundamental questions and, at the same time, highlights the potential physiological roles of the primo vascular structures in acupuncture. PMID:23606882

  15. The primo vascular structures alongside nervous system: its discovery and functional limitation.

    PubMed

    Park, Eun-Sung; Kim, Hee Young; Youn, Dong-Ho

    2013-01-01

    The primo vascular structures comprising primo nodes and vessels (originally called Bonghan corpuscles and ducts, resp.) have recently been suggested to be the anatomical correlate of acupuncture, a therapeutic technique used in oriental medicine. Although the primo vascular structures have been observed in many parts of animals, including the nervous system, using anatomical methodologies, its physiological functions are still unclear. This paper summarizes the reports on the primo vascular structures, particularly in the nervous system and its surroundings, as well as the electrophysiological properties of cells in the primo nodes. In addition, recent reports examining the potential roles of the primo vascular structures in acupuncture are discussed. This review raises some fundamental questions and, at the same time, highlights the potential physiological roles of the primo vascular structures in acupuncture.

  16. Creating perfused functional vascular channels using 3D bio-printing technology.

    PubMed

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

    2014-09-01

    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 5 mm 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 was 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.

  17. The interrelations between malfunctioning DNA damage response (DDR) and the functionality of the neuro-glio-vascular unit.

    PubMed

    Barzilai, Ari

    2013-08-01

    A hallmark of neurodegenerative diseases is impairment of certain aspects of "brain functionality". Brain functionality is defined as the total input and output of the brain's neural circuits and networks. A given brain degenerative disorder does not deregulate total brain functionality but rather the activity of specific circuits in a given network, affecting their organization and topology, their cell numbers, their cellular functionality, and the interactions between neural circuits. Similarly, our concept of neurodegenerative diseases, which for many years revolved around neural survival or death, has now been extended to emphasize the role of glia. In particular, the role of glial cells in neuro-vascular communication is now known to be central to the effect of insults to the nervous system. In addition, a malfunctioning vascular system likely plays a role in the etiology of certain neurodegenerative diseases. Thus, the symptoms of neurodegenerative or more correctly brain degenerative disease are, to a very large extent, a result of impairment in glial cells that lead to pathological neuro-vascular interactions that, in turn, generate a rather "hostile" environment in which the neurons fail to function. These events lead to systematic neural cell death on a scale that appears to be proportional to the severity of the neurological deficit.

  18. Effect of sulodexide on vascular responses and liver mitochondrial function in diabetic rats.

    PubMed

    Dobiaš, L; Petrová, M; Vojtko, R; Uličná, O; Vančová, O; Kristová, V

    2015-01-01

    This study investigates the effects of long-term treatment with sulodexide (SLX) on norepinephrine (NE)-induced contractions, acetylcholine(Ach)-induced relaxations, acute cyclooxygenase blockade by diclofenac (DIC) in isolated femoral arteries (FA) and the parameters of oxidative phosporylation in liver mitochondria. 15-weeks old Wistar rats were divided into four groups: control (C; injected with saline solution), treated control (C+SLX), diabetic (DM) and treated diabetic (DM+SLX). Diabetes was induced with a single i.v. dose of streptozotocin (STZ) 45 mg.kg(-1). SLX was administered i.p., at dose 100 IU.kg(-1) daily for 5 weeks. Vascular responses of isolated femoral arteries were measured using Mulvany-Halpern myograph. Respiratory function of the mitochondria was determined using voltamperometric method on oxygraph Gilson. In diabetic rats the amplitude of maximal response to NE was elevated. DIC pretreatment decreased the amplitudes of NE-induced contractions in all groups of rats. SLX treatment decreased sensitivity of FA to NE and caused higher relaxatory responses to Ach in C and DM. Oxygen consumption and phosphorylation rates ([QO(2)(S(3))], [QO(2)(S(4))] and (OPR)) and respiratory control ratio (RCR) were decreased in the mitochondria of DM rats. Mitochondria of C rats were not affected with SLX treatment. Administration of SLX in DM rats was associated with increase of RCR, other parameters were not affected. Our findings suggest that SLX treatment might be associated with vasculoprotective effects during diabetes and improvement of mitochondrial function.

  19. Fibroblast growth factor signaling affects vascular outgrowth and is required for the maintenance of blood vessel integrity.

    PubMed

    De Smet, Frederik; Tembuyser, Bieke; Lenard, Anna; Claes, Filip; Zhang, Jie; Michielsen, Christof; Van Schepdael, Ann; Herbert, Jean-Marc; Bono, Françoise; Affolter, Markus; Dewerchin, Mieke; Carmeliet, Peter

    2014-10-23

    Angiogenesis contributes to the development of numerous disorders. Even though fibroblast growth factors (FGFs) were discovered as mediators of angiogenesis more than 30 years ago, their role in developmental angiogenesis still remains elusive. We use a recently described chemical probe, SSR128129E (SSR), that selectively inhibits the action of multiple FGF receptors (FGFRs), in combination with the zebrafish model to examine the role of FGF signaling in vascular development. We observe that while FGFR signaling is less important for vessel guidance, it affects vascular outgrowth and is especially required for the maintenance of blood vessel integrity by ensuring proper cell-cell junctions between endothelial cells. In conclusion, our work illustrates the power of a small molecule probe to reveal insights into blood vessel formation and stabilization and thus of broad interest to the vascular biology community.

  20. Modular Small Diameter Vascular Grafts with Bioactive Functionalities

    PubMed Central

    Neufurth, Meik; Wang, Xiaohong; Tolba, Emad; Dorweiler, Bernhard; Schröder, Heinz C.; Link, Thorben; Diehl-Seifert, Bärbel; Müller, Werner E. G.

    2015-01-01

    We report the fabrication of a novel type of artificial small diameter blood vessels, termed biomimetic tissue-engineered blood vessels (bTEBV), with a modular composition. They are composed of a hydrogel scaffold consisting of two negatively charged natural polymers, alginate and a modified chitosan, N,O-carboxymethyl chitosan (N,O-CMC). Into this biologically inert scaffold two biofunctionally active biopolymers are embedded, inorganic polyphosphate (polyP) and silica, as well as gelatin which exposes the cell recognition signal, Arg-Gly-Asp (RGD). These materials can be hardened by exposure to Ca2+ through formation of Ca2+ bridges between the polyanions, alginate, N,O-CMC, and polyP (alginate-Ca2+-N,O-CMC-polyP). The bTEBV are formed by pressing the hydrogel through an extruder into a hardening solution, containing Ca2+. In this universal scaffold of the bTEBV biomaterial, polycations such as poly(l-Lys), poly(d-Lys) or a His/Gly-tagged RGD peptide (three RGD units) were incorporated, which promote the adhesion of endothelial cells to the vessel surface. The mechanical properties of the biopolymer material (alginate-Ca2+-N,O-CMC-polyP-silica) revealed a hardness (elastic modulus) of 475 kPa even after a short incubation period in CaCl2 solution. The material of the artificial vascular grafts (bTEBVs with an outer size 6 mm and 1.8 mm, and an inner diameter 4 mm and 0.8 mm, respectively) turned out to be durable in 4-week pulsatile flow experiments at an alternating pressure between 25 and 100 mbar (18.7 and 75.0 mm Hg). The burst pressure of the larger (smaller) vessels was 850 mbar (145 mbar). Incorporation of polycationic poly(l-Lys), poly(d-Lys), and especially the His/Gly-tagged RGD peptide, markedly increased the adhesion of human, umbilical vein/vascular endothelial cells, EA.HY926 cells, to the surface of the hydrogel. No significant effect of the polyP samples on the clotting of human plasma is measured. We propose that the metabolically degradable

  1. Important Roles of Ring Finger Protein 112 in Embryonic Vascular Development and Brain Functions.

    PubMed

    Tsou, Jen-Hui; Yang, Ying-Chen; Pao, Ping-Chieh; Lin, Hui-Ching; Huang, Nai-Kuei; Lin, Shih-Ting; Hsu, Kuei-Sen; Yeh, Che-Ming; Lee, Kuen-Haur; Kuo, Chu-Jen; Yang, De-Ming; Lin, Jiann-Her; Chang, Wen-Chang; Lee, Yi-Chao

    2017-04-01

    Rnf112 is a member of the RING finger protein family. The expression of Rnf112 is abundant in the brain and is regulated during brain development. Our previous study has revealed that Rnf112 can promote neuronal differentiation by inhibiting the progression of the cell cycle in cell models. In this study, we further revealed the important functions of Rnf112 in embryo development and in adult brain. Our data showed that most of the Rnf112 (-/-) embryos exhibited blood vascular defects and died in utero. Upon further investigation, we found that the survival rate of homozygous Rnf112 knockout mice in 129/sv and C57BL/6 mixed genetic background was increased. The survived newborns of Rnf112 (-/-) mice manifested growth retardation as indicated by smaller size and a reduced weight. Although the overall organization of the brain did not appear to be severely affected in Rnf112 (-/-) mice, using in vivo 3D MRI imaging, we found that when compared to wild-type littermates, brains of Rnf112 (-/-) mice were smaller. In addition, Rnf112 (-/-) mice displayed impairment of brain functions including motor balance, and spatial learning and memory. Our results provide important aspects for the study of Rnf112 gene functions.

  2. Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function After Hemorrhagic Shock.

    PubMed

    Deng, Xiyun; Cao, Yanna; Huby, Maria P; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A; Doursout, Marie-Francoise; Holcomb, John B; Wade, Charles E; Ko, Tien C

    2016-01-01

    Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared with normal individuals, plasma adiponectin levels decreased to 49% in HS patients before resuscitation (P < 0.05) and increased to 64% post-resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared with baseline (P < 0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS.

  3. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

  4. Effects of cranberry juice consumption on vascular function in patients with coronary artery disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk. The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease. We completed an acute pilot study with no placebo...

  5. Inhibition of angiopoietin-1 (ANGPT1) affects vascular integrity in ovarian hyperstimulation syndrome (OHSS).

    PubMed

    Scotti, Leopoldina; Abramovich, Dalhia; Pascuali, Natalia; Durand, Luis Haro; Irusta, Griselda; de Zúñiga, Ignacio; Tesone, Marta; Parborell, Fernanda

    2016-04-01

    Ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation with gonadotrophins following human chorionic gonadotrophin (hCG) administration. The relationship between hCG and OHSS is partly mediated via the production of angiogenic factors, such as vascular endothelial growth factor A (VEGFA) and angiopoietins (ANGPTs). Here, we investigated the effect of ANGPT1 inhibition on ovarian angiogenesis in follicular fluid (FF) from women at risk of OHSS, using the chorioallantoic membrane (CAM) of quail embryos as an experimental model. We also analysed cytoskeletal changes and endothelial junction protein expression induced by this FF in the presence or absence of an ANGPT1-neutralising antibody in endothelial cell cultures. The presence of this antibody restored the number of vascular branch points and integrin αvβ3 levels in the CAMs to control values. ANGPT1 inhibition in FF from OHSS patients also restored the levels of claudin-5, vascular endothelial cadherin and phosphorylated β-catenin and partially reversed actin redistribution in endothelial cells. Our findings suggest that ANGPT1 increases pathophysiological angiogenesis in patients at risk of OHSS by acting on tight and adherens junction proteins. Elucidating the mechanisms by which ANGPT1 regulates vascular development and cell-cell junctions in OHSS will contribute to identifying new therapeutic targets for the treatment of human diseases with aberrant vascular leakage.

  6. Functional regulation of ClC-3 in the migration of vascular smooth muscle cells.

    PubMed

    Ganapathi, Sindura B; Wei, Shun-Guang; Zaremba, Angelika; Lamb, Fred S; Shears, Stephen B

    2013-01-01

    Migration of vascular smooth muscle cells (VSMCs) into neointima contributes to atherosclerosis and restenosis. This migration requires coordinated plasmalemmal fluxes of water and ions. Here, we show that aortic VSMC migration depends on the regulation of transmembrane Cl(-) flux by ClC-3, a Cl(-) channel/transporter. The contribution of ClC-3 to plasmalemmal Cl(-) current was studied in VSMCs by electrophysiological recordings. Cl(-) current was negligible in cells perfused with 0 [Ca(2+)]. Raising intracellular [Ca(2+)] to 0.5 μM activated a Cl(-) current (I(Cl.Ca)), approximately half of which was eliminated on inhibition by KN-93 of calmodulin-dependent protein kinase II. I(Cl.Ca) was also halved by inositol-3,4,5,6-tetrakisphosphate, a cellular signal with the biological function of specifically preventing calmodulin-dependent protein kinase II from activating I(Cl.Ca). Gene disruption of ClC-3 reduced I(Cl.Ca) by 50%. Moreover, I(Cl.Ca) in the ClC-3 null VSMCs was not affected by either KN-93 or inositol-3,4,5,6-tetrakisphosphate. We conclude that I(Cl.Ca) is composed of 2 components, one is ClC-3 independent whereas the other is ClC-3 dependent, activated by calmodulin-dependent protein kinase II and inhibited by inositol-3,4,5,6-tetrakisphosphate. We also assayed VSMC migration in transwell assays. Migration was halved in ClC-3 null cells versus wild-type cells. In addition, inhibition of ClC-3 by niflumic acid, KN-93, or inositol-3,4,5,6-tetrakisphosphate each reduced cell migration in wild-type cells but not in ClC-3 null cells. These cell-signaling roles of ClC-3 in VSMC migration suggest new therapeutic approaches to vascular remodeling diseases.

  7. Motor and memory function in rat models of cyanide toxicity and vascular occlusion induced ischemic injury.

    PubMed

    Ogundele, Olalekan Michael; Adeniyi, Philip Adeyemi; Ajonijebu, Duyilemi Chris; Abdulbasit, Amin; Cobham, Ansa Emmanuel; Ishola, Azeez Olakunle; Balogun, Gbolahan Wasiu

    2014-09-01

    Although oxidative stress is characteristic of global vascular occlusion and cyanide toxicity, the pattern of cerebral metabolism reconditioning and rate of progression or reversal of neural tissue damage differ for both forms of ischemia. Thus, it is important to compare cognitive and motor functions in both models of ischemia involving cyanide treatment (CN) and vascular occlusion (VO). Adult Wistar rats (N=30) were divided into three groups; VO (n=12), CN (n=12) and Control-CO (n=6). The CN was treated with 30mg/Kg of potassium cyanide (KCN); VO was subjected to global vascular occlusion-both for duration of 10 days. The control (CO) was fed on normal rat chow and water for the same duration. At day 10, the test and control groups (CN, VO and CO) were subjected to motor function tests (Table edge tests and Open Field Test) and memory function tests (Y-Maze and Novel object recognition) while the withdrawal groups CN-I and VO-I were subjected to the same set of tests at day 20 (the withdrawal phase). The results show that both cyanide toxicity and vascular occlusion caused a decline in motor and memory function when compared with the control. Also, the cyanide treatment produced a more rapid decline in these behavioral parameters when compared with the vascular occlusion during the treatment phase. After the withdrawal phase, cyanide treatment (CN-I) showed either an improvement or restoration of motor and memory function when compared to the CN and control. Withdrawal of vascular occlusion caused no improvement, and in some cases a decline in motor and memory function. In conclusion, cyanide toxicity caused a decline in motor and memory function after the treatment while vascular occlusion caused no significant decline in cognition and motor function at this time. After the withdrawal phase, the effect of cyanide toxicity was reduced and significant improvements were observed in the behavioral tests (motor and cognitive), while a decline in these functions were

  8. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice.

    PubMed

    Feng, Dilu; Menger, Michael D; Wang, Hongbo; Laschke, Matthias W

    2014-02-01

    In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE(+)) and without luminal epithelium (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE(-) fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE(+) fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE(+) lesions compared with LE(-) lesions. In addition, we found that many GFP(+) microvessels grew outside the LE(-) lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  9. Vascular Cognitive Impairment.

    PubMed

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.

  10. Function, Role, and Clinical Application of MicroRNAs in Vascular Aging

    PubMed Central

    Zhan, Jun-Kun; Wang, Yan-Jiao; Tan, Pan; Chen, Yi-Yin; Deng, Hui-Qian

    2016-01-01

    Vascular aging, a specific type of organic aging, is related to age-dependent changes in the vasculature, including atherosclerotic plaques, arterial stiffness, fibrosis, and increased intimal thickening. Vascular aging could influence the threshold, process, and severity of various cardiovascular diseases, thus making it one of the most important risk factors in the high mortality of cardiovascular diseases. As endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main cell biological basis of these pathology changes of the vasculature, the structure and function of ECs and VSMCs play a key role in vascular aging. MicroRNAs (miRNAs), small noncoding RNAs, have been shown to regulate the expression of multiple messenger RNAs (mRNAs) posttranscriptionally, contributing to many crucial aspects of cell biology. Recently, miRNAs with functions associated with aging or aging-related diseases have been studied. In this review, we will summarize the reported role of miRNAs in the process of vascular aging with special emphasis on EC and VSMC functions. In addition, the potential application of miRNAs to clinical practice for the diagnosis and treatment of cardiovascular diseases will also be discussed. PMID:28097140

  11. Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.

    PubMed

    Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H; English, Mark; Talcott, Susanne; Jaffe, Iris Z; Christou, Demetra D

    2016-01-01

    Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61±1 years; mean±SE, 53-79 years) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4 mg) following eplerenone (100 mg/dose, 2 doses, 24h between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9±0.5 to 5.6±0.6%, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOS(Ser1177) to total eNOS (1.53±0.08 vs. 1.29±0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9±1.9 vs. 21.0±1.5%, P=0.5 and systolic/diastolic blood pressure: 135/77±4/2 vs. 134/77±4/2 mmHg, P≥0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure.

  12. Acute Effect of Mineralocorticoid Receptor Antagonism on Vascular Function in Healthy Older Adults

    PubMed Central

    Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H.; English, Mark; Talcott, Susanne; Jaffe, Iris Z.; Christou, Demetra D.

    2015-01-01

    Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61±1 y; mean ± SE, 53–79 y) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4mg) following eplerenone (100 mg/dose, 2 doses, 24 hours between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9±0.5 to 5.6±0.6 %, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOSSer1177 to total eNOS (1.53±0.08 vs. 1.29±0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9±1.9 vs. 21.0±1.5 %, P=0.5 and systolic/diastolic blood pressure: 135/77±4/2 vs. 134/77± 4/2 mmHg, P ≥0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure. PMID:26639352

  13. Sox17 drives functional engraftment of endothelium converted from non-vascular cells

    PubMed Central

    Schachterle, William; Badwe, Chaitanya R.; Palikuqi, Brisa; Kunar, Balvir; Ginsberg, Michael; Lis, Raphael; Yokoyama, Masataka; Elemento, Olivier; Scandura, Joseph M.; Rafii, Shahin

    2017-01-01

    Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function. PMID:28091527

  14. Beta-lactam antibiotic-mediated changes in platelet reactivity and vascular endothelial functions.

    PubMed

    Togna, G I; Togna, A R; Caprino, L

    2001-05-01

    To evaluate vascular and platelet compatibility of intravenous administration of beta-lactam antibiotics, we assessed the effects of therapeutic concentrations of ceftriaxone, aztreonam, and ceftazidime on platelet reactivity to different agonists (sodium arachidonate, collagen and adenosine diphosphate) and on selected vascular endothelial functions (adenosine diphosphatase activity, prostacyclin production and t-PA release). Ceftriaxone and, to a lesser degree, aztreonam, enhanced platelet reactivity, evaluated as onset of platelet aggregating response, and increased thromboxane production to subthreshold concentrations of arachidonate. There was no modification in platelet reactivity after ceftazidime treatment. Ceftriaxone and ceftazidime, but not aztreonam, inhibited endothelial adenosine diphosphatase activity. Prostacyclin production and t-PA release were inhibited only by ceftriaxone at high concentrations. While it is difficult to establish which marker (platelet or endothelial functions) has more clinical reference in human vascular compatibility, it seems feasible to consider aztreonam the most compatible of the beta-lactams studied.

  15. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

    PubMed Central

    Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

  16. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct.

    PubMed

    Valarmathi, Mani T; Fuseler, John W; Davis, Jeffrey M; Price, Robert L

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty.

  17. Does iron deficiency anemia affect olfactory function?

    PubMed

    Dinc, Mehmet Emre; Dalgic, Abdullah; Ulusoy, Seckin; Dizdar, Denizhan; Develioglu, Omer; Topak, Murat

    2016-07-01

    Conclusion This study found a negative effect of IDA on olfactory function. IDA leads to a reduction in olfactory function, and decreases in hemoglobin levels result in further reduction in olfactory function. Objective This study examined the effects of iron-deficiency anemia (IDA) on olfactory function. Method The study enrolled 50 IDA patients and 50 healthy subjects. Olfactory function was evaluated using the Sniffin' Sticks olfactory test. The diagnosis of IDA was made according to World Health Organization (WHO) criteria. Results Patients with IDA had a significantly lower threshold, discrimination, and identification (TDI) value, and a lower threshold compared with the control group. However, there were no significant differences between the groups in terms of smell selectivity values.

  18. Methane transport and emissions from soil as affected by water table and vascular plants

    PubMed Central

    2013-01-01

    Background The important greenhouse gas (GHG) methane is produced naturally in anaerobic wetland soils. By affecting the production, oxidation and transport of methane to the atmosphere, plants have a major influence upon the quantities emitted by wetlands. Different species and functional plant groups have been shown to affect these processes differently, but our knowledge about how these effects are influenced by abiotic factors such as water regime and temperature remains limited. Here we present a mesocosm experiment comparing eight plant species for their effects on internal transport and overall emissions of methane under contrasting hydrological conditions. To quantify how much methane was transported internally through plants (the chimney effect), we blocked diffusion from the soil surface with an agar seal. Results We found that graminoids caused higher methane emissions than forbs, although the emissions from mesocosms with different species were either lower than or comparable to those from control mesocosms with no plant (i.e. bare soil). Species with a relatively greater root volume and a larger biomass exhibited a larger chimney effect, though overall methane emissions were negatively related to plant biomass. Emissions were also reduced by lowering the water table. Conclusions We conclude that plant species (and functional groups) vary in the degree to which they transport methane to the atmosphere. However, a plant with a high capacity to transport methane does not necessarily emit more methane, as it may also cause more rhizosphere oxidation of methane. A shift in plant species composition from graminoids to forbs and/or from low to high productive species may lead to reduction of methane emissions. PMID:24010540

  19. Nitinol-based Nanotubular and Nanowell Coatings for the Modulation of Human Vascular Cell Functions

    NASA Astrophysics Data System (ADS)

    Lee, Phin Peng

    Current approaches to reducing restenosis do not balance the reduction of vascular smooth muscle cell proliferation with the increase in the healing of the endothelium. Here, I present my study on the synthesis and characterization of a nanotubular coating on Nitinol substrates. I found that the coating demonstrated 'pro-healing' properties by increasing primary human aortic endothelial cell spreading, migration and collagen and elastin production. Certain cellular functions such as collagen and elastin production were also found to be affected by changes in nanotube diameter. The coating also reduced the proliferation and mRNA expression of collagen I and MMP2 for primary human aortic smooth muscle cells. I will also demonstrate the synthesis of a nanowell coating on Nitinol stents as well as an additional poly(lactic-co-glycolic acid) coating on top of the nanowells that has the potential for controlling drug release. These findings demonstrate the potential for the coatings to aid in the prevention of restenosis and sets up future explorations of ex vivo and in vivo studies.

  20. Polymeric active coatings with functionality in vascular applications.

    PubMed

    Aguilar, María Rosa; Rodríguez, Gema; Fernández, Mar; Gallardo, Alberto; San Román, Julio

    2002-12-01

    Copolymers containing functional groups with activity as antiaggregating agents for platelets, based on random chains of metacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)]benzoate, TH, and 2-acrylamido-2-metylpropanesulfonic acid, AMPS, with AMPS molar fractions ranging from 0.1 to 0.4, have been prepared. The spectroscopical characterization and the in vitro swelling behavior have been studied, as well as the surface free energy, showing the copolymers an appropriate surface properties from a haemocompatible point of view. Preliminary in vitro tests using human blood have shown a promising antiaggregating behavior.

  1. Function and regulation of large conductance Ca(2+)-activated K+ channel in vascular smooth muscle cells.

    PubMed

    Hu, Xiang-Qun; Zhang, Lubo

    2012-09-01

    Large conductance Ca(2+)-activated K(+) (BK(Ca)) channels are abundantly expressed in vascular smooth muscle cells. Activation of BK(Ca) channels leads to hyperpolarization of cell membrane, which in turn counteracts vasoconstriction. Therefore, BK(Ca) channels have an important role in regulation of vascular tone and blood pressure. The activity of BK(Ca) channels is subject to modulation by various factors. Furthermore, the function of BK(Ca) channels are altered in both physiological and pathophysiological conditions, such as pregnancy, hypertension and diabetes, which has dramatic impacts on vascular tone and hemodynamics. Consequently, compounds and genetic manipulation that alter activity and expression of the channel might be of therapeutic interest.

  2. Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2.

    PubMed

    Fachinger, G; Deutsch, U; Risau, W

    1999-10-21

    During development of the vertebrate vascular system essential signals are transduced via protein-tyrosine phosphorylation. Null-mutations of receptor-tyrosine kinase (RTK) genes expressed in endothelial cells (ECs) display early lethal vascular phenotypes. We aimed to identify endothelial protein-tyrosine phosphatases (PTPs), which should have similar importance in EC-biology. A murine receptor-type PTP was identified by a degenerated PCR cloning approach from endothelial cells (VE-PTP). By in situ hybridization this phosphatase was found to be specifically expressed in vascular ECs throughout mouse development. In experiments using GST-fusion proteins, as well as in transient transfections, trapping mutants of VE-PTP co-precipitated with the Angiopoietin receptor Tie-2, but not with the Vascular Endothelial Growth Factor receptor 2 (VEGFR-2/Flk-1). In addition, VE-PTP dephosphorylates Tie-2 but not VEGFR-2. We conclude that VE-PTP is a Tie-2 specific phosphatase expressed in ECs, and VE-PTP phosphatase activity serves to specifically modulate Angiopoietin/Tie-2 function. Based on its potential role as a regulator of blood vessel morphogenesis and maintainance, VE-PTP is a candidate gene for inherited vascular malformations similar to the Tie-2 gene.

  3. Alterations in vascular function in primary aldosteronism: a cardiovascular magnetic resonance imaging study.

    PubMed

    Mark, P B; Boyle, S; Zimmerli, L U; McQuarrie, E P; Delles, C; Freel, E M

    2014-02-01

    Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV). We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass. Subjects with PA had significantly lower aortic distensibility and higher PWV compared with EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including ageing. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular ageing. As expected, aortic distensibility and PWV were closely correlated. These results demonstrate that PA patients display increased arterial stiffness compared with EH, independent of vascular ageing. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.

  4. Vascular risk factors, endothelial function, and carotid thickness in patients with migraine: relationship to atherosclerosis.

    PubMed

    Hamed, Sherifa A; Hamed, Enas A; Ezz Eldin, Azza M; Mahmoud, Nagia M

    2010-03-01

    Recent studies indicated that migraine is associated with specific vascular risk profile. However, the functional and structural vascular abnormalities in migraine are rarely addressed. We evaluated the vascular risk factors, endothelial function, and carotid artery (CA)-intima-media thickness (IMT), segregators of preclinical atherosclerosis, in migraineurs. This preliminary study included 63 adults with headache (migraine with aura [n=14], migraine without aura [n=24], transformed migraine [n=6], and tension headache [n=19]) and 35 matched healthy subjects. The following vascular risks were assessed: body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressures (DBP), serum levels of C-reactive protein, fasting glucose, fasting insulin, total cholesterol, and triglycerides. Plasma endothelin (ET)-1, a vasoactive peptide produced by vascular smooth muscle cells and marker for endothelial injury and atherosclerosis, was measured. Endothelial-dependent vasoreactivity was assessed using brachial artery flow-mediated dilatation (FMD) in response to hyperemia. CA-IMT, structural marker of early atherosclerosis, was measured. Compared with control subjects, SBP, DBP, glucose, insulin, ET-1, and CA-IMT were elevated with migraine. FMD% was inversely correlated with SBP (P < .001), DBP (P < .01), glucose (P < .001), and insulin levels (P < .01). CA-IMT was correlated with BMI (P < .05), SBP (P < .01), total cholesterol (P < .01), triglycerides (P < .001), glucose (P < .001), insulin (P < .01), and FMD% (P < .05). In multivariate analysis, ET-1 was correlated with duration of illness, SBP, DBP, glucose, insulin, IMT, and FMD%. We conclude that endothelial injury, impaired endothelial vasoreactivity, and increased CA-IMT occur with migraine and are associated with vascular risk factors that strongly suggest that migraine could be a risk for atherosclerosis.

  5. Impaired renal function impacts negatively on vascular stiffness in patients with coronary artery disease

    PubMed Central

    2013-01-01

    Background Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. Methods We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology. Results Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = −0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress. Conclusions Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease. PMID:23937620

  6. Vascular Health and Cognitive Function in Older Adults with Cardiovascular Disease.

    PubMed

    Forman, Daniel E; Cohen, Ronald A; Hoth, Karin F; Haley, Andreana P; Poppas, Athena; Moser, David J; Gunstad, John; Paul, Robert H; Jefferson, Angela L; Tate, David F; Ono, Makoto; Wake, Nicole; Gerhard-Herman, Marie

    2008-02-01

    BACKGROUND: We hypothesized that changes in vascular flow dynamics resulting from age and cardiovascular disease (CVD) would correlate to neurocognitive capacities, even in adults screened to exclude dementia and neurological disease. We studied endothelial-dependent as well as endothelial-independent brachial responses in older adults with CVD to study the associations of vascular responses with cognition. Comprehensive neurocognitive testing was used to discern which specific cognitive domain(s) correlated to the vascular responses. METHODS: Eighty-eight independent, community-dwelling older adults (70.02+7.67 years) with mild to severe CVD were recruited. Enrollees were thoroughly screened to exclude neurological disease and dementia. Flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery responses were assessed using 2-d ultrasound. Cognitive functioning was assessed using comprehensive neuropsychological testing. Linear regression analyses were used to evaluate the relationships between the endothelial-dependent and endothelial-independent vascular flow dynamics and specific domains of neurocognitive function. RESULTS: Endothelial-dependent and endothelial-independent brachial artery responses both correlated with neurocognitive testing indices. The strongest independent relationship was between endothelial function and measures of attention-executive functioning. CONCLUSIONS: Endothelial-dependent and endothelial-independent vascular responsiveness correlate with neurocognitive performance among older CVD patients, particularly in the attention-executive domain. While further study is needed to substantiate causal relationships, our data demonstrate that brachial responses serve as important markers of risk for common neurocognitive changes. Learning and behavior-modifying therapeutic strategies that compensate for such common, insidious neurocognitive limitations will likely improve caregiving efficacy.

  7. The effect of age on the relationship between cardiac and vascular function.

    PubMed

    Houghton, David; Jones, Thomas W; Cassidy, Sophie; Siervo, Mario; MacGowan, Guy A; Trenell, Michael I; Jakovljevic, Djordje G

    2016-01-01

    Age-related changes in cardiac and vascular function are associated with increased risk of cardiovascular mortality and morbidity. The aim of the present study was to define the effect of age on the relationship between cardiac and vascular function. Haemodynamic and gas exchange measurements were performed at rest and peak exercise in healthy individuals. Augmentation index was measured at rest. Cardiac power output, a measure of overall cardiac function, was calculated as the product of cardiac output and mean arterial blood pressure. Augmentation index was significantly higher in older than younger participants (27.7 ± 10.1 vs. 2.5 ± 10.1%, P<0.01). Older people demonstrated significantly higher stroke volume and mean arterial blood pressure (P<0.05), but lower heart rate (145 ± 13 vs. 172 ± 10 beats/min, P<0.01) and peak oxygen consumption (22.5 ± 5.2 vs. 41.2 ± 8.4 ml/kg/min, P<0.01). There was a significant negative relationship between augmentation index and peak exercise cardiac power output (r=-0.73, P=0.02) and cardiac output (r=-0.69, P=0.03) in older participants. Older people maintain maximal cardiac function due to increased stroke volume. Vascular function is a strong predictor of overall cardiac function in older but in not younger people.

  8. A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

    PubMed

    Neven, Ellen; De Schutter, Tineke M; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Behets, Geert J

    2014-01-01

    The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.

  9. Effects of Swimming and Cycling Exercise Intervention on Vascular Function in Patients With Osteoarthritis.

    PubMed

    Alkatan, Mohammed; Machin, Daniel R; Baker, Jeffrey R; Akkari, Amanda S; Park, Wonil; Tanaka, Hirofumi

    2016-01-01

    Swimming exercise is an ideal and excellent form of exercise for patients with osteoarthritis (OA). However, there is no scientific evidence that regular swimming reduces vascular dysfunction and inflammation and elicits similar benefits compared with land-based exercises such as cycling in terms of reducing vascular dysfunction and inflammation in patients with OA. Forty-eight middle-aged and older patients with OA were randomly assigned to swimming or cycling training groups. Cycling training was included as a non-weight-bearing land-based comparison group. After 12 weeks of supervised exercise training, central arterial stiffness, as determined by carotid-femoral pulse wave velocity, and carotid artery stiffness, through simultaneous ultrasound and applanation tonometry, decreased significantly after both swimming and cycling training. Vascular endothelial function, as determined by brachial flow-mediated dilation, increased significantly after swimming but not after cycling training. Both swimming and cycling interventions reduced interleukin-6 levels, whereas no changes were observed in other inflammatory markers. In conclusion, these results indicate that regular swimming exercise can exert similar or even superior effects on vascular function and inflammatory markers compared with land-based cycling exercise in patients with OA who often has an increased risk of developing cardiovascular disease.

  10. Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder

    PubMed Central

    Moises, H W; Wollschläger, D; Binder, H

    2015-01-01

    In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P<0.001), vasoregulation (that is, perivascular (P<0.001) and shear stress (P<0.01), cerebral ischemia (P<0.001), neurodevelopment (P<0.001) and postischemic repair (P<0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P=0.020) combined with downregulated synaptic (P=0.005) genes, and ND/repair (P=0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina. PMID:26261884

  11. Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder.

    PubMed

    Moises, H W; Wollschläger, D; Binder, H

    2015-08-11

    In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P < 0.001), vasoregulation (that is, perivascular (P < 0.001) and shear stress (P < 0.01), cerebral ischemia (P < 0.001), neurodevelopment (P < 0.001) and postischemic repair (P < 0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P = 0.020) combined with downregulated synaptic (P = 0.005) genes, and ND/repair (P = 0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina.

  12. Evolutionary diversification in stickleback affects ecosystem functioning.

    PubMed

    Harmon, Luke J; Matthews, Blake; Des Roches, Simone; Chase, Jonathan M; Shurin, Jonathan B; Schluter, Dolph

    2009-04-30

    Explaining the ecological causes of evolutionary diversification is a major focus of biology, but surprisingly little has been said about the effects of evolutionary diversification on ecosystems. The number of species in an ecosystem and their traits are key predictors of many ecosystem-level processes, such as rates of productivity, biomass sequestration and decomposition. Here we demonstrate short-term ecosystem-level effects of adaptive radiation in the threespine stickleback (Gasterosteus aculeatus) over the past 10,000 years. These fish have undergone recent parallel diversification in several lakes in coastal British Columbia, resulting in the formation of two specialized species (benthic and limnetic) from a generalist ancestor. Using a mesocosm experiment, we demonstrate that this diversification has strong effects on ecosystems, affecting prey community structure, total primary production, and the nature of dissolved organic materials that regulate the spectral properties of light transmission in the system. However, these ecosystem effects do not simply increase in their relative strength with increasing specialization and species richness; instead, they reflect the complex and indirect consequences of ecosystem engineering by sticklebacks. It is well known that ecological factors influence adaptive radiation. We demonstrate that adaptive radiation, even over short timescales, can have profound effects on ecosystems.

  13. Circadian Variation in Vascular Function and Regenerative Capacity in Healthy Humans

    PubMed Central

    Mheid, Ibhar Al; Corrigan, Frank; Shirazi, Farheen; Veledar, Emir; Li, Qunna; Alexander, Wayne R.; Taylor, W. Robert; Waller, Edmund K.; Quyyumi, Arshed A.

    2014-01-01

    Background Progenitor cells (PCs) are mobilized in response to vascular injury to effect regeneration and repair. Recruitment of PCs requires intact nitric oxide (NO) synthesis by endothelial cells, and their number and activity correlate with cardiovascular disease risk burden and future outcomes. Whereas cardiovascular vulnerability exhibits a robust circadian rhythm, the 24‐hour variation of PCs and their inter‐relation with vascular function remain unknown. We investigated the circadian variation of PCs and vascular function with the hypothesis that this will parallel the pattern observed for cardiovascular events (CVEs). Methods and Results In 15 healthy subjects (9 men, 37±16 years), circulating PCs and vascular function were measured at 8 am, noon, 4 pm, 8 pm, midnight, 4 am (only PCs counts), and 8 am the following day. Circulating PCs were enumerated as mononuclear cells (MNCs; CD45med) that express CD34 as well as CD133, and their activity was assessed as the number of colonies formed by culturing MNCs. Vascular function was evaluated by measurement of endothelium‐dependent, flow‐mediated vasodilation (FMD) of the brachial artery and tonometry‐derived indices of arterial stiffness. Higher CD34+ and CD34+/CD133+ cell counts were observed at 8 pm than any other time of the day (P‐ANOVA=0.038 and <0.001; respectively) and were lowest at 8 am. PC colony formation was highest at midnight (P‐ANOVA=0.045) and lowest in the morning hours. FMD was highest at midnight and lowest at 8 am and 8 pm, and systemic arterial stiffness was greatest at 8 am and lowest at 4 pm and midnight (P‐ANOVA=0.03 and 0.01; respectively). Conclusion A robust circadian variation in PC counts and vascular function occurs in healthy humans and both exhibit an unfavorable profile in the morning hours that parallels the preponderance of CVEs at these times. Whether these changes are precipitated by awakening and time‐dependent physical activity or governed by the

  14. Exercise training improves vascular endothelial function in patients with type 1 diabetes.

    PubMed

    Fuchsjäger-Mayrl, Gabriele; Pleiner, Johannes; Wiesinger, Günther F; Sieder, Anna E; Quittan, Michael; Nuhr, Martin J; Francesconi, Claudia; Seit, Hans-Peter; Francesconi, Mario; Schmetterer, Leopold; Wolzt, Michael

    2002-10-01

    OBJECTIVE-Impaired endothelial function of resistance and conduit arteries can be detected in patients with type 1 diabetes. We studied whether a persistent improvement of endothelial function can be achieved by regular physical training. RESEARCH DESIGN AND METHODS-The study included 26 patients with type 1 diabetes of 20 +/- 10 years' duration and no overt angiopathy; 18 patients (42 +/- 10 years old) participated in a bicycle exercise training program, and 8 patients with type 1 diabetes (33 +/- 11 years old) served as control subjects. Vascular function of conduit arteries was assessed by flow-mediated and endothelium-independent dilation of the brachial artery and of resistance vessels by the response of ocular fundus pulsation amplitudes to intravenous N(G)-monomethyl-L-arginine (L-NMMA) at baseline, after 2 and 4 months of training, and 8 months after cessation of regular exercise. RESULTS-Training increased peak oxygen uptake (VO(2max)) by 13% after 2 months and by 27% after 4 months (P = 0.04). Flow-mediated dilation (FMD) of the brachial artery increased from 6.5 +/- 1.1 to 9.8 +/- 1.1% (P = 0.04) by training. L-NMMA administration decreased fundus pulsation amplitude (FPA) by 9.1 +/- 0.9% before training and by 13.4 +/- 1.5% after 4 months of training (P = 0.02). VO(2max), FMD, and FPA were unchanged in the control group. Vascular effects from training were abrogated 8 months after cessation of exercise. CONCLUSIONS-Our study demonstrates that aerobic exercise training can improve endothelial function in different vascular beds in patients with long-standing type 1 diabetes, who are at considerable risk for diabetic angiopathy. However, the beneficial effect on vascular function is not maintained in the absence of exercise.

  15. ECM-mimetic heparin glycosamioglycan-functionalized surface favors constructing functional vascular smooth muscle tissue in vitro.

    PubMed

    Zhang, Jimin; Wang, Jianing; Wei, Yongzhen; Gao, Cheng; Chen, Xuejiao; Kong, Wei; Kong, Deling; Zhao, Qiang

    2016-10-01

    Contractile vascular smooth muscle accounts for the normal physiological function of artery. Heparin, as a native glycosaminoglycan, has been well known for its important function in promoting or maintaining the contractile phenotype of vascular smooth muscle cells (VSMCs). In this study, heparin-functionalized non-woven poly(ε-caprolactone) (PCL) mat was fabricated by a facile and efficient surface modification protocol, which enables the control of surface heparin density within a broad range. Surface heparization remarkably increased the hydrophilicity of PCL, and reduced platelet adhesion. MTT assay showed that VSMC proliferation was evidently inhibited on the heparin-functionalized PCL surface in a dose-dependent manner. Gene analysis confirmed that surface heparization also promoted the transition of VSMCs from synthetic phenotype to contractile one. Furthermore, with a proper surface density of heparin, it allowed VSMCs to grow in a certain rate, while exhibiting contractile phenotype. Culture of VSMCs on a modified PCL mat with moderate heparin density (PCL-Hep-20) for 2 days resulted in a confluent layer of contractile smooth muscle cells. These data suggest that the heparin-modified PCL scaffolds may be a promising candidate to generate functional vascular tissues in vitro.

  16. Novel Vascular Malformation in an Affected Newborn with Deletion Del(4)(q31.3)

    PubMed Central

    de León Ojeda, Norma Elena; Soriano-Torres, Michel; Cabrera, Mercedes J.; Benítez Ramos, Dunia Bárbara

    2012-01-01

    We report on a newborn male patient with a terminal deletion in the long arm of the chromosome 4 with a congenital heart defect unreported before in association with this syndrome. The patient had multiple congenital anomalies including a pointed duplicated fingernail, low set posteriorly rotated ears, large anterior fontanel, micrognathia, glabellar capillary vascular malformation, and Interrupted Aortic Arch type C. The patient died due to multiple congenital malformations; a peripheral chromosome analysis showed 46, XY, del(4)(q31.3) de novo. The only reported case with the same deletion was a male newborn that exhibited the pattern of minor anomalies of deletion 4q31 syndrome. The parents were cytogenetically normal. We compare clinical signs to other cases with a deletion in long arm of chromosome 4. PMID:23320208

  17. Identification of chemical components of combustion emissions that affect pro-atherosclerotic vascular responses in mice

    PubMed Central

    Seilkop, Steven K.; Campen, Matthew J.; Lund, Amie K.; McDonald, Jacob D.; Mauderly, Joe L.

    2012-01-01

    Combustion emissions cause pro-atherosclerotic responses in apolipoprotein E-deficient (ApoE/−) mice, but the causal components of these complex mixtures are unresolved. In studies previously reported, ApoE−/− mice were exposed by inhalation 6 h/day for 50 consecutive days to multiple dilutions of diesel or gasoline exhaust, wood smoke, or simulated “downwind” coal emissions. In this study, the analysis of the combined four-study database using the Multiple Additive Regression Trees (MART) data mining approach to determine putative causal exposure components regardless of combustion source is reported. Over 700 physical–chemical components were grouped into 45 predictor variables. Response variables measured in aorta included endothelin-1, vascular endothelin growth factor, three matrix metalloproteinases (3, 7, 9), metalloproteinase inhibitor 2, heme-oxygenase-1, and thiobarbituric acid reactive substances. Two or three predictors typically explained most of the variation in response among the experimental groups. Overall, sulfur dioxide, ammonia, nitrogen oxides, and carbon monoxide were most highly predictive of responses, although their rankings differed among the responses. Consistent with the earlier finding that filtration of particles had little effect on responses, particulate components ranked third to seventh in predictive importance for the eight response variables. MART proved useful for identifying putative causal components, although the small number of pollution mixtures (4) can provide only suggestive evidence of causality. The potential independent causal contributions of these gases to the vascular responses, as well as possible interactions among them and other components of complex pollutant mixtures, warrant further evaluation. PMID:22486345

  18. Engineering micropatterned surfaces to modulate the function of vascular stem cells

    SciTech Connect

    Li, Jennifer; Wu, Michelle; Chu, Julia; Sochol, Ryan; Patel, Shyam

    2014-02-21

    Highlights: • We examine vascular stem cell function on microgrooved and micropost patterned polymer substrates. • 10 μm microgrooved surfaces significantly lower VSC proliferation but do not modulate calcified matrix deposition. • Micropost surfaces significantly lower VSC proliferation and decrease calcified matrix deposition. - Abstract: Multipotent vascular stem cells have been implicated in vascular disease and in tissue remodeling post therapeutic intervention. Hyper-proliferation and calcified extracellular matrix deposition of VSC cause blood vessel narrowing and plaque hardening thereby increasing the risk of myocardial infarct. In this study, to optimize the surface design of vascular implants, we determined whether micropatterned polymer surfaces can modulate VSC differentiation and calcified matrix deposition. Undifferentiated rat VSC were cultured on microgrooved surfaces of varied groove widths, and on micropost surfaces. 10 μm microgrooved surfaces elongated VSC and decreased cell proliferation. However, microgrooved surfaces did not attenuate calcified extracellular matrix deposition by VSC cultured in osteogenic media conditions. In contrast, VSC cultured on micropost surfaces assumed a dendritic morphology, were significantly less proliferative, and deposited minimal calcified extracellular matrix. These results have significant implications for optimizing the design of cardiovascular implant surfaces.

  19. Construction of a fucoidan/laminin functional multilayer to direction vascular cell fate and promotion hemocompatibility.

    PubMed

    Ye, Changrong; Wang, Yan; Su, Hong; Yang, Ping; Huang, Nan; F Maitz, Manfred; Zhao, Anshan

    2016-07-01

    Surface biofunctional modification of cardiovascular stents is a versatile approach to reduce the adverse effects after implantation. In this work, a novel multifunctional coating was fabricated by coimmobilization of the sulfated polysaccharide of brown algae fucoidan and laminin to biomimic the vascular intimal conditions in order to support rapid endothelialization, prevent restenosis and improve hemocompatibility. The surface properties of the coating such as hydrophilicity, bonding density of biomolecules and stability were evaluated and optimized. According to the biocompatibility tests, the fucoidan/laminin multilayer coated surface displayed less platelet adhesion with favorable anticoagulant property. In addition, the fucoidan/laminin complex showed function to selectively regulate vascular cells growth behavior. The proliferation of endothelial cells (ECs) on the fucoidan/laminin biofunctional coating was significantly promoted. For the smooth muscle cells (SMCs), inhibitory effects on cell adhesion and proliferation were observed. In conclusion, the fucoidan/laminin biofunctional coating was successfully fabricated with desirable anticoagulant and endothelialization properties which show a promising application in the vascular devices such as vascular stents or grafts surface modification.

  20. Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Cañas, Daniel; Herrera, Emilio A.; García-Herrera, Claudio; Celentano, Diego; Krause, Bernardo J.

    2017-01-01

    Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of FGR on the vasoactive and biomechanical properties of umbilical and systemic vessels in fetal guinea pigs. Methods: FGR was induced by implanting ameroid occluders at mid-gestation in uterine arteries of pregnant guinea pigs, whilst the control group was exposed to simulated surgery. At the term of gestation, systemic arteries (aorta, carotid and femoral) and umbilical vessels were isolated to determine ex vivo contractile and biomechanical responses (stretch-stress until rupture) on a wire myograph, as well as opening angle and residual stresses. Histological characteristics in tissue samples were measured by van Gieson staining. Results: Aorta and femoral arteries from FGR showed an increased in biomechanical markers of stiffness (p < 0.01), contractile capacity (p < 0.05) and relative media thickness (p < 0.01), but a reduced internal diameter (p < 0.001), compared with controls. There were no differences in the biomechanical properties of carotid and umbilical from control and FGR fetuses, but FGR umbilical arteries had a decreased contractile response to KCl (p < 0.05) along with a reduced relative media thickness (p < 0.05). Conclusion: Altogether, these changes in functional, mechanical and morphological properties suggest that FGR is associated with a heterogeneous pro-constrictive vascular remodeling affecting mainly the lower body fetal arteries. These effects would be set during a pathologic pregnancy in order to sustain the fetal blood redistribution in the FGR and may persist up to adulthood increasing the risk of a cardiovascular disease. PMID:28344561

  1. Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus).

    PubMed

    Cañas, Daniel; Herrera, Emilio A; García-Herrera, Claudio; Celentano, Diego; Krause, Bernardo J

    2017-01-01

    Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of FGR on the vasoactive and biomechanical properties of umbilical and systemic vessels in fetal guinea pigs. Methods: FGR was induced by implanting ameroid occluders at mid-gestation in uterine arteries of pregnant guinea pigs, whilst the control group was exposed to simulated surgery. At the term of gestation, systemic arteries (aorta, carotid and femoral) and umbilical vessels were isolated to determine ex vivo contractile and biomechanical responses (stretch-stress until rupture) on a wire myograph, as well as opening angle and residual stresses. Histological characteristics in tissue samples were measured by van Gieson staining. Results: Aorta and femoral arteries from FGR showed an increased in biomechanical markers of stiffness (p < 0.01), contractile capacity (p < 0.05) and relative media thickness (p < 0.01), but a reduced internal diameter (p < 0.001), compared with controls. There were no differences in the biomechanical properties of carotid and umbilical from control and FGR fetuses, but FGR umbilical arteries had a decreased contractile response to KCl (p < 0.05) along with a reduced relative media thickness (p < 0.05). Conclusion: Altogether, these changes in functional, mechanical and morphological properties suggest that FGR is associated with a heterogeneous pro-constrictive vascular remodeling affecting mainly the lower body fetal arteries. These effects would be set during a pathologic pregnancy in order to sustain the fetal blood redistribution in the FGR and may persist up to adulthood increasing the risk of a cardiovascular disease.

  2. Enhanced vascular function after acute fat-rich snacking in healthy males.

    PubMed

    Liu, Yibin; Daleke, David L; Fly, Alyce D

    2012-08-01

    Diets high in fat are associated with vascular dysfunction. Frequent snacking may exacerbate this problem by extending the postprandial state. We hypothesized that repeated fat-rich mixed snacks would impair peripheral endothelial function and increase oxidative stress, a purported causal factor. Second, we hypothesized that feeding a quantity of snack based on the subject's body size would not cause different effects from feeding a fixed or constant size snack. A crossover design was used where 10 healthy males followed 2 repeated-snack regimens (fixed and variable based on body surface area), 1 week apart. Each regimen consisted of 2 snacks, fed 4 hours apart (0 and 4 hours). Markers of vascular function (reactive hyperemia index [RHI]), oxidative stress, and antioxidant capacity were measured before and after each snack. Peripheral vascular function improved from fasting to 2 hours after snack 1 (RHI(2h-0h), P = .010), but the change before and after snack 2, RHI(6h-4h), was negative (P = .026), indicating reduced endothelial function after repeated snacking. The oxidative stress marker changed over time (P = .043), increasing after snack 1 and decreasing before snack 2, with no change after snack 2. The antioxidant marker increased 2 hours after each snack (P = .003). Responses to fixed snacks over time were not different from variable snacks, although power was low; the effect size was large for antioxidant capacity, medium for oxidative stress, and small for RHI. Snacking after fasting resulted in a transiently improved peripheral vascular response that disappeared with a second snack. Antioxidant capacity appeared to help limit oxidative stress from repeated snacking in these healthy male subjects.

  3. Changes in vascular plant functional types drive carbon cycling in peatlands

    NASA Astrophysics Data System (ADS)

    Zeh, Lilli; Bragazza, Luca; Erhagen, Björn; Limpens, Juul; Kalbitz, Karsten

    2016-04-01

    Northern peatlands store a large organic carbon (C) pool that is highly exposed to future environmental changes with consequent risk of releasing enormous amounts of C. Biotic changes in plant community structure and species abundance might have an even stronger impact on soil organic C dynamics in peatlands than the direct effects of abiotic changes. Therefore, a sound understanding of the impact of vegetation dynamics on C cycling will help to better predict the response of peatlands to environmental changes. Here, we aimed to assess the role of plant functional types (PFTs) in affecting peat decomposition in relation to climate warming. To this aim, we selected two peatlands at different altitude (i.e. 1300 and 1700 m asl) on the south-eastern Alps of Italy. The two sites represent a contrast in temperature, overall vascular plant biomass and relative ericoids abundance, with the highest biomass and ericoids occurrence at the low latitude. Within the sites we selected 20 plots of similar microtopographical position and general vegetation type (hummocks). All plots contained both graminoids and ericoids and had a 100% cover of Sphagnum mosses. The plots were subjected to four treatments (control, and three clipping treatments) in which we selectively removed aboveground biomass of ericoids, graminoids or both to explore the contribution of the different PFTs for soil respiration (n=5) and peat chemistry. Peat chemical composition was determined by the analysis of C and N and their stable isotopes in association with pyrolysis GC/MS. Soil respiration was measured after clipping with a Licor system. Preliminary findings suggest that peat decomposition pathway and rate depend on plant species composition and particularly on differences in root activity between PFTs. Finally, this study underlines the importance of biotic drivers to predict the effects of future environmental changes on peatland C cycling.

  4. Assessment of vascular function in Mexican women exposed to polycyclic aromatic hydrocarbons from wood smoke.

    PubMed

    Ruiz-Vera, Tania; Pruneda-Álvarez, Lucia G; Ochoa-Martínez, Ángeles C; Ramírez-GarcíaLuna, José L; Pierdant-Pérez, Mauricio; Gordillo-Moscoso, Antonio A; Pérez-Vázquez, Francisco J; Pérez-Maldonado, Iván N

    2015-09-01

    The use of solid fuels for cooking and heating is likely to be the largest source of indoor air pollution on a global scale; these fuels emit substantial amounts of toxic pollutants such as polycyclic aromatic hydrocarbons (PAHs) when used in simple cooking stoves (such as open "three-stone" fires). Moreover, indoor air pollution from biomass fuels is considered an important risk factor for human health. The aim of this study was to evaluate the relationship between exposure to PAHs from wood smoke and vascular dysfunction; in a group of Mexican women that use biomass combustion as their main energy source inside their homes. We used 1-hydroxypyrene (1-OHP) as an exposure biomarker to PAHs and it was assessed using high performance liquid chromatography. The endothelium-dependent vasodilation was assessed through a vascular reactivity compression test performed with a pneumatic cuff under visualization of the brachial artery using high resolution ultrasonography (HRU). Assessment of the carotid intima-media thickness (CIMT) was used as an atherosclerosis biomarker (also assessed using HRU); and clinical parameters such as anthropometry, blood pressure, glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, among others were also evaluated. The mean concentration of urinary 1-OHP found in exposed women was 0.46±0.32μmol/mol Cr (range: 0.086-1.23μmol/mol Cr). Moreover, vascular dysfunction (diminished endothelium dependent vasodilation) was found in 45% of the women participating in the study. Association between vascular function and 1-OHP levels was found to be significant through a logistic regression analysis (p=0.034; r(2)=0.1329). Furthermore, no association between CIMT and clinical parameters, urinary 1-OHP levels or vascular dysfunction was found. Therefore, with the information obtained in this study, we advocate for the need to implement programs to reduce the risk of exposure to PAHs in communities that use biomass fuels as a main

  5. Circulating Adipokines and Vascular Function: Cross-sectional Association in a Community-Based Cohort

    PubMed Central

    Zachariah, Justin P.; Hwang, Susan; Hamburg, Naomi M.; Benjamin, Emelia J.; Larson, Martin G.; Levy, Daniel; Vita, Joseph A.; Sullivan, Lisa M.; Mitchell, Gary F.; Vasan, Ramachandran S.

    2016-01-01

    Adipokines may be potential mediators of the association between excess adiposity and vascular dysfunction. We assessed the cross-sectional associations of circulating adipokines with vascular stiffness in a community-based cohort of younger adults. We related circulating concentrations of leptin and leptin receptor, adiponectin, retinol binding protein 4, and fatty acid binding protein 4 to vascular stiffness measured by arterial tonometry in 3505 Framingham Third Generation cohort participants free of cardiovascular disease (mean age 40 years, 53% women). Separate regression models estimated the relations of each adipokine to mean arterial pressure and aortic stiffness, as carotid femoral pulse wave velocity, adjusting for age, sex, smoking, heart rate, height, antihypertensive treatment, total and high-density lipoprotein cholesterol, diabetes, alcohol consumption, estimated glomerular filtration rate, glucose and C-reactive protein. Models evaluating aortic stiffness also were adjusted for mean arterial pressure. Mean arterial pressure was positively associated with blood retinol binding protein 4, fatty acid binding protein 4, and leptin concentrations (all P<0.001) and inversely with adiponectin (p=0.002). In fully adjusted models, mean arterial pressure was positively associated with retinol binding protein 4 and leptin receptor levels (p<0.002 both). In fully adjusted models, aortic stiffness was positively associated with fatty acid binding protein 4 concentrations (p=0.02), but inversely with leptin and leptin receptor levels (p≤0.03 both). In our large community-based sample, circulating concentrations of select adipokines were associated with vascular stiffness measures, consistent with the hypothesis that adipokines may influence vascular function and may contribute to the relation between obesity and hypertension. PMID:26628673

  6. Vascular wall function in insulin-resistant JCR:LA-cp rats: role of male and female sex.

    PubMed

    O'Brien, S F; Russell, J C; Dolphin, P J; Davidge, S T

    2000-08-01

    Vascular wall function was assessed in obese insulin-resistant (cp/cp) and lean normal (+/?), male and female, JCR:LA-cp rats. Both male and female cp/cp rats showed enhanced maximum contractility in response to norepinephrine; impaired smooth muscle in response to sodium nitroprusside, a nitric oxide (NO) donor; and impaired relaxation in response to acetylcholine (ACh), compared with their lean counterparts. The abnormalities were similar in male and female cp/cp rats. The NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), inhibited ACh-mediated relaxation significantly in male rats, both cp/cp and +/?. The inhibition of ACh-mediated relaxation by L-NAME in +/? females was less, with no reduction in maximal relaxation, and was absent in cp/cp females. These effects suggest that the relative importance of NO in the endothelial modulation of smooth muscle contractility is greater in male rats. The results are consistent with a decreased role for endothelial NO in the cp/cp rats of both sexes and a reduction in NO-independent cholinergic relaxation in the male cp/cp rat. This NO-independent mechanism is not affected in the female cp/cp rats. The relatively small differences between males and females in smooth muscle cell and vascular function may contribute to sex-related differences in the atherogenesis, vasospasm, and ischemic damage associated with the obese insulin-resistant state.

  7. Effect of recombinant human growth hormone administration on body composition and vascular function and structure in old male Wistar rats.

    PubMed

    Castillo, Carmen; Cruzado, Mar; Ariznavarreta, Carmen; Gil-Loyzaga, Pablo; Lahera, Vicente; Cachofeiro, Victoria; Tresguerres, Jesús A F

    2005-01-01

    The process of ageing affects negatively both cardiovascular system and body composition. On the other hand, the hormones of the somatotrophic axis, growth hormone (GH) and insulin-like growth factor-I (IGF-I), whose production is reduced by age, are involved in the regulation of the cardiovascular system. The aim of this study was to investigate the effect of GH on body composition, vascular function and structure in old male rats. Old (20 months) and adult (4 months) male Wistar rats were used. One group of old animals was treated with GH for 4 weeks. Periepididimary fat weight, Specific Gravity Index (SGI), dose responses to Acetylcholine (ACh), Isoproterenol (Iso), Phenylephrine (Phe) and ACh in the presence of NG-nitro-L: -arginine metylester (L-NAME; ACh + L-NAME), as well as vascular morphology in aortic rings, were studied. Old rats showed increased fat weight and decreased SGI as compared to adult animals. GH increased SGI and tended to reduce fat weight. Old rats showed an impairment in the vasodilator response to ACh and Iso; GH significantly improved the vasodilatation induced by Iso, whereas the response to ACh was not significantly enhanced by GH treatment. There were no significant differences between adult and old rats in the contractile response to Phe, and GH did not show any effect. Contraction induced by ACh + L-NAME was higher in old rats as compared to adults, and treatment with GH significantly reduced this response. Aortic media area was increased in old rats, and GH administration reduced this parameter. In conclusion, GH shows beneficial effects on body composition, as well as on vascular function and morphology in old male rats.

  8. Smooth Muscle Endothelin B Receptors Regulate Blood Pressure but Not Vascular Function or Neointimal Remodeling.

    PubMed

    Miller, Eileen; Czopek, Alicja; Duthie, Karolina M; Kirkby, Nicholas S; van de Putte, Elisabeth E Fransen; Christen, Sibylle; Kimmitt, Robert A; Moorhouse, Rebecca; Castellan, Raphael F P; Kotelevtsev, Yuri V; Kuc, Rhoda E; Davenport, Anthony P; Dhaun, Neeraj; Webb, David J; Hadoke, Patrick W F

    2017-02-01

    The role of smooth muscle endothelinB (ETB) receptors in regulating vascular function, blood pressure (BP), and neointimal remodeling has not been established. Selective knockout mice were generated to address the hypothesis that loss of smooth muscle ETB receptors would reduce BP, alter vascular contractility, and inhibit neointimal remodeling. ETB receptors were selectively deleted from smooth muscle by crossing floxed ETB mice with those expressing cre-recombinase controlled by the transgelin promoter. Functional consequences of ETB deletion were assessed using myography. BP was measured by telemetry, and neointimal lesion formation induced by femoral artery injury. Lesion size and composition (day 28) were analyzed using optical projection tomography, histology, and immunohistochemistry. Selective deletion of ETB was confirmed by genotyping, autoradiography, polymerase chain reaction, and immunohistochemistry. ETB-mediated contraction was reduced in trachea, but abolished from mesenteric veins, of knockout mice. Induction of ETB-mediated contraction in mesenteric arteries was also abolished in these mice. Femoral artery function was unaltered, and baseline BP modestly elevated in smooth muscle ETB knockout compared with controls (+4.2±0.2 mm Hg; P<0.0001), but salt-induced and ETB blockade-mediated hypertension were unaltered. Circulating endothelin-1 was not altered in knockout mice. ETB-mediated contraction was not induced in femoral arteries by incubation in culture medium or lesion formation, and lesion size was not altered in smooth muscle ETB knockout mice. In the absence of other pathology, ETB receptors in vascular smooth muscle make a small but significant contribution to ETB-dependent regulation of BP. These ETB receptors have no effect on vascular contraction or neointimal remodeling.

  9. Smooth Muscle Endothelin B Receptors Regulate Blood Pressure but Not Vascular Function or Neointimal Remodeling

    PubMed Central

    Miller, Eileen; Czopek, Alicja; Duthie, Karolina M.; Kirkby, Nicholas S.; van de Putte, Elisabeth E. Fransen; Christen, Sibylle; Kimmitt, Robert A.; Moorhouse, Rebecca; Castellan, Raphael F.P.; Kotelevtsev, Yuri V.; Kuc, Rhoda E.; Davenport, Anthony P.; Dhaun, Neeraj; Webb, David J.

    2017-01-01

    The role of smooth muscle endothelinB (ETB) receptors in regulating vascular function, blood pressure (BP), and neointimal remodeling has not been established. Selective knockout mice were generated to address the hypothesis that loss of smooth muscle ETB receptors would reduce BP, alter vascular contractility, and inhibit neointimal remodeling. ETB receptors were selectively deleted from smooth muscle by crossing floxed ETB mice with those expressing cre-recombinase controlled by the transgelin promoter. Functional consequences of ETB deletion were assessed using myography. BP was measured by telemetry, and neointimal lesion formation induced by femoral artery injury. Lesion size and composition (day 28) were analyzed using optical projection tomography, histology, and immunohistochemistry. Selective deletion of ETB was confirmed by genotyping, autoradiography, polymerase chain reaction, and immunohistochemistry. ETB-mediated contraction was reduced in trachea, but abolished from mesenteric veins, of knockout mice. Induction of ETB-mediated contraction in mesenteric arteries was also abolished in these mice. Femoral artery function was unaltered, and baseline BP modestly elevated in smooth muscle ETB knockout compared with controls (+4.2±0.2 mm Hg; P<0.0001), but salt-induced and ETB blockade–mediated hypertension were unaltered. Circulating endothelin-1 was not altered in knockout mice. ETB-mediated contraction was not induced in femoral arteries by incubation in culture medium or lesion formation, and lesion size was not altered in smooth muscle ETB knockout mice. In the absence of other pathology, ETB receptors in vascular smooth muscle make a small but significant contribution to ETB-dependent regulation of BP. These ETB receptors have no effect on vascular contraction or neointimal remodeling. PMID:28028193

  10. Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response.

    PubMed

    Venturelli, Massimo; Layec, Gwenael; Trinity, Joel; Hart, Corey R; Broxterman, Ryan M; Richardson, Russell S

    2017-01-01

    Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 ± 1 mmHg), whereas both HR and CO increased from baseline (6.0 ± 1.1 beats/min, and 0.8 ± 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 ± 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 ± 189 ml/min; 11.9 ± 1.5 ml·min(-1)·mmHg(-1), respectively) and sPLM (878 ± 119 ml/min; 10.9 ± 1.6 ml·min(-1)·mmHg(-1), respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically.

  11. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis

    PubMed Central

    2014-01-01

    Background The nootropic neuroprotective peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) has proved efficient in the therapy of brain stroke; however, the molecular mechanisms underlying its action remain obscure. Our genome-wide study was designed to investigate the response of the transcriptome of ischemized rat brain cortex tissues to the action of Semax in vivo. Results The gene-expression alteration caused by the action of the peptide Semax was compared with the gene expression of the “ischemia” group animals at 3 and 24 h after permanent middle cerebral artery occlusion (pMCAO). The peptide predominantly enhanced the expression of genes related to the immune system. Three hours after pMCAO, Semax influenced the expression of some genes that affect the activity of immune cells, and, 24 h after pMCAO, the action of Semax on the immune response increased considerably. The genes implicated in this response represented over 50% of the total number of genes that exhibited Semax-induced altered expression. Among the immune-response genes, the expression of which was modulated by Semax, genes that encode immunoglobulins and chemokines formed the most notable groups. In response to Semax administration, 24 genes related to the vascular system exhibited altered expression 3 h after pMCAO, whereas 12 genes were changed 24 h after pMCAO. These genes are associated with such processes as the development and migration of endothelial tissue, the migration of smooth muscle cells, hematopoiesis, and vasculogenesis. Conclusions Semax affects several biological processes involved in the function of various systems. The immune response is the process most markedly affected by the drug. Semax altered the expression of genes that modulate the amount and mobility of immune cells and enhanced the expression of genes that encode chemokines and immunoglobulins. In conditions of rat brain focal ischemia, Semax influenced the expression of genes that promote the formation and

  12. The effect of age on the relationship between cardiac and vascular function

    PubMed Central

    Houghton, David; Jones, Thomas W.; Cassidy, Sophie; Siervo, Mario; MacGowan, Guy A.; Trenell, Michael I.; Jakovljevic, Djordje G.

    2016-01-01

    Age-related changes in cardiac and vascular function are associated with increased risk of cardiovascular mortality and morbidity. The aim of the present study was to define the effect of age on the relationship between cardiac and vascular function. Haemodynamic and gas exchange measurements were performed at rest and peak exercise in healthy individuals. Augmentation index was measured at rest. Cardiac power output, a measure of overall cardiac function, was calculated as the product of cardiac output and mean arterial blood pressure. Augmentation index was significantly higher in older than younger participants (27.7 ± 10.1 vs. 2.5 ± 10.1%, P < 0.01). Older people demonstrated significantly higher stroke volume and mean arterial blood pressure (P < 0.05), but lower heart rate (145 ± 13 vs. 172 ± 10 beats/min, P < 0.01) and peak oxygen consumption (22.5 ± 5.2 vs. 41.2 ± 8.4 ml/kg/min, P < 0.01). There was a significant negative relationship between augmentation index and peak exercise cardiac power output (r = −0.73, P = 0.02) and cardiac output (r = −0.69, P = 0.03) in older participants. Older people maintain maximal cardiac function due to increased stroke volume. Vascular function is a strong predictor of overall cardiac function in older but in not younger people. PMID:26590322

  13. Effects of swimming training on blood pressure and vascular function in adults >50 years of age.

    PubMed

    Nualnim, Nantinee; Parkhurst, Kristin; Dhindsa, Mandeep; Tarumi, Takashi; Vavrek, Jackie; Tanaka, Hirofumi

    2012-04-01

    Swimming is ideal for older adults because it includes minimum weight-bearing stress and decreased heat load. However, there is very little information available concerning the effects of regular swimming exercise on vascular risks. We determined if regular swimming exercise would decrease arterial blood pressure (BP) and improve vascular function. Forty-three otherwise healthy adults >50 years old (60 ± 2) with prehypertension or stage 1 hypertension and not on any medication were randomly assigned to 12 weeks of swimming exercise or attention time controls. Before the intervention period there were no significant differences in any of the variables between groups. Body mass, adiposity, and plasma concentrations of glucose and cholesterol did not change in either group throughout the intervention period. Casual systolic BP decreased significantly from 131 ± 3 to 122 ± 4 mm Hg in the swimming training group. Significant decreases in systolic BP were also observed in ambulatory (daytime) and central (carotid) BP measurements. Swimming exercise produced a 21% increase in carotid artery compliance (p <0.05). Flow-mediated dilation and cardiovagal baroreflex sensitivity improved after the swim training program (p <0.05). There were no significant changes in any measurements in the control group that performed gentle relaxation exercises. In conclusion, swimming exercise elicits hypotensive effects and improvements in vascular function in previously sedentary older adults.

  14. Plant CLE peptides from two distinct functional classes synergistically induce division of vascular cells

    PubMed Central

    Whitford, Ryan; Fernandez, Ana; De Groodt, Ruth; Ortega, Esther; Hilson, Pierre

    2008-01-01

    The Clavata3 (CLV3)/endosperm surrounding region (CLE) signaling peptides are encoded in large plant gene families. CLV3 and the other A-type CLE peptides promote cell differentiation in root and shoot apical meristems, whereas the B-type peptides (CLE41–CLE44) do not. Instead, CLE41 inhibits the differentiation of Zinnia elegans tracheary elements. To test whether CLE genes might code for antagonistic or synergistic functions, peptides from both types were combined through overexpression within or application onto Arabidopsis thaliana seedlings. The CLE41 peptide (CLE41p) promoted proliferation of vascular cells, although delaying differentiation into phloem and xylem cell lineages. Application of CLE41p or overexpression of CLE41 did not suppress the terminal differentiation of the root and shoot apices triggered by A-type CLE peptides. However, in combination, A-type peptides enhanced all of the phenotypes associated with CLE41 gain-of-function, leading to massive proliferation of vascular cells. This proliferation relied on auxin signaling because it was enhanced by exogenous application of a synthetic auxin, decreased by an auxin polar transport inhibitor, and abolished by a mutation in the Monopteros auxin response factor. These findings highlight that vascular patterning is a process controlled in time and space by different CLE peptides in conjunction with hormonal signaling. PMID:19011104

  15. A review about biomarkers for the investigation of vascular function and impairment in diabetes mellitus

    PubMed Central

    Derosa, Giuseppe; Maffioli, Pamela

    2016-01-01

    The aim of this review was to analyze the main biomarkers of vascular function and impairment in patients with type 2 diabetes. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched. We concluded that proatherogenic adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E selectin) and inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α) were elevated in type 2 diabetes mellitus. Their increased expression and release contribute to the accelerated atherogenesis typical of these patients. For these reasons, the early identification of high levels of these biomarkers will help to establish new strategies to reduce cardiovascular complications. PMID:27877049

  16. Segmental analysis of indocyanine green pharmacokinetics for the reliable diagnosis of functional vascular insufficiency

    NASA Astrophysics Data System (ADS)

    Kang, Yujung; Lee, Jungsul; An, Yuri; Jeon, Jongwook; Choi, Chulhee

    2011-03-01

    Accurate and reliable diagnosis of functional insufficiency of peripheral vasculature is essential since Raynaud phenomenon (RP), most common form of peripheral vascular insufficiency, is commonly associated with systemic vascular disorders. We have previously demonstrated that dynamic imaging of near-infrared fluorophore indocyanine green (ICG) can be a noninvasive and sensitive tool to measure tissue perfusion. In the present study, we demonstrated that combined analysis of multiple parameters, especially onset time and modified Tmax which means the time from onset of ICG fluorescence to Tmax, can be used as a reliable diagnostic tool for RP. To validate the method, we performed the conventional thermographic analysis combined with cold challenge and rewarming along with ICG dynamic imaging and segmental analysis. A case-control analysis demonstrated that segmental pattern of ICG dynamics in both hands was significantly different between normal and RP case, suggesting the possibility of clinical application of this novel method for the convenient and reliable diagnosis of RP.

  17. A review about biomarkers for the investigation of vascular function and impairment in diabetes mellitus.

    PubMed

    Derosa, Giuseppe; Maffioli, Pamela

    2016-01-01

    The aim of this review was to analyze the main biomarkers of vascular function and impairment in patients with type 2 diabetes. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched. We concluded that proatherogenic adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E selectin) and inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α) were elevated in type 2 diabetes mellitus. Their increased expression and release contribute to the accelerated atherogenesis typical of these patients. For these reasons, the early identification of high levels of these biomarkers will help to establish new strategies to reduce cardiovascular complications.

  18. Role of Vitamin C in the Function of the Vascular Endothelium

    PubMed Central

    Harrison, Fiona E.

    2013-01-01

    Abstract Significance: Vitamin C, or ascorbic acid, has long been known to participate in several important functions in the vascular bed in support of endothelial cells. These functions include increasing the synthesis and deposition of type IV collagen in the basement membrane, stimulating endothelial proliferation, inhibiting apoptosis, scavenging radical species, and sparing endothelial cell-derived nitric oxide to help modulate blood flow. Although ascorbate may not be able to reverse inflammatory vascular diseases such as atherosclerosis, it may well play a role in preventing the endothelial dysfunction that is the earliest sign of many such diseases. Recent Advances: Beyond simply preventing scurvy, evidence is mounting that ascorbate is required for optimal function of many dioxygenase enzymes in addition to those involved in collagen synthesis. Several of these enzymes regulate the transcription of proteins involved in endothelial function, proliferation, and survival, including hypoxia-inducible factor-1α and histone and DNA demethylases. More recently, ascorbate has been found to acutely tighten the endothelial permeability barrier and, thus, may modulate access of ascorbate and other molecules into tissues and organs. Critical Issues: The issue of the optimal cellular content of ascorbate remains unresolved, but it appears that low millimolar ascorbate concentrations are normal in most animal tissues, in human leukocytes, and probably in the endothelium. Although there may be little benefit of increasing near maximal cellular ascorbate concentrations in normal people, many diseases and conditions have either systemic or localized cellular ascorbate deficiency as a cause for endothelial dysfunction, including early atherosclerosis, sepsis, smoking, and diabetes. Future Directions: A key focus for future studies of ascorbate and the vascular endothelium will likely be to determine the mechanisms and clinical relevance of ascorbate effects on endothelial

  19. Mechanics and Function of the Pulmonary Vasculature: Implications for Pulmonary Vascular Disease and Right Ventricular Function

    PubMed Central

    Lammers, Steven; Scott, Devon; Hunter, Kendall; Tan, Wei; Shandas, Robin; Stenmark, Kurt R.

    2012-01-01

    The relationship between cardiac function and the afterload against which the heart muscle must work to circulate blood throughout the pulmonary circulation is defined by a complex interaction between many coupled system parameters. These parameters range broadly and incorporate system effects originating primarily from three distinct locations: input power from the heart, hydraulic impedance from the large conduit pulmonary arteries, and hydraulic resistance from the more distal microcirculation. These organ systems are not independent, but rather, form a coupled system in which a change to any individual parameter affects all other system parameters. The result is a highly nonlinear system which requires not only detailed study of each specific component and the effect of disease on their specific function, but also requires study of the interconnected relationship between the microcirculation, the conduit arteries, and the heart in response to age and disease. Here, we investigate systems-level changes associated with pulmonary hypertensive disease progression in an effort to better understand this coupled relationship. PMID:23487595

  20. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

    PubMed

    Wyrwoll, Caitlin S; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R; Rog-Zielinska, Eva A; Moran, Carmel M; Seckl, Jonathan R; Chapman, Karen E; Holmes, Megan C

    2016-05-31

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.

  1. Acute Effect of High-Intensity Eccentric Exercise on Vascular Endothelial Function in Young Men.

    PubMed

    Choi, Youngju; Akazawa, Nobuhiko; Zempo-Miyaki, Asako; Ra, Song-Gyu; Shiraki, Hitoshi; Ajisaka, Ryuichi; Maeda, Seiji

    2016-08-01

    Choi, Y, Akazawa, N, Zempo-Miyaki, A, Ra, S-G, Shiraki, H, Ajisaka, R, and Maeda, S. Acute effect of high-intensity eccentric exercise on vascular endothelial function in young men. J Strength Cond Res 30(8): 2279-2285, 2016-Increased central arterial stiffness is as an independent risk factor for cardiovascular disease. Evidence regarding the effects of high-intensity resistance exercise on vascular endothelial function and central arterial stiffness is conflicting. The purpose of this study was to examine the effects of acute high-intensity eccentric exercise on vascular endothelial function and central arterial stiffness. We evaluated the acute changes in endothelium-dependent flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and arterial stiffness after high-intensity eccentric exercise. Seven healthy, sedentary men (age, 24 ± 1 year) performed maximal eccentric elbow flexor exercise using their nondominant arm. Before and 45 minutes after eccentric exercise, carotid arterial compliance and brachial artery FMD and L-FMC in the nonexercised arm were measured. Carotid arterial compliance was significantly decreased, and β-stiffness index significantly increased after eccentric exercise. Brachial FMD was significantly reduced after eccentric exercise, whereas there was no significant difference in brachial L-FMC before and after eccentric exercise. A positive correlation was detected between change in arterial compliance and change in FMD (r = 0.779; p ≤ 0.05), and a negative correlation was detected between change in β-stiffness index and change in FMD (r = -0.891; p < 0.01) with eccentric exercise. In this study, acute high-intensity eccentric exercise increased central arterial stiffness; this increase was accompanied by a decrease in endothelial function caused by reduced endothelium-dependent vasodilation but not by a change in endothelium-dependent vasoconstriction.

  2. Experimental studies of mitochondrial function in CADASIL vascular smooth muscle cells

    SciTech Connect

    Viitanen, Matti; Sundström, Erik; Baumann, Marc; Tikka, Saara

    2013-02-01

    Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a familiar fatal progressive degenerative disorder characterized by cognitive decline, and recurrent stroke in young adults. Pathological features include a dramatic reduction of brain vascular smooth muscle cells and severe arteriopathy with the presence of granular osmophilic material in the arterial walls. Here we have investigated the cellular and mitochondrial function in vascular smooth muscle cell lines (VSMCs) established from CADASIL mutation carriers (R133C) and healthy controls. We found significantly lower proliferation rates in CADASIL VSMC as compared to VSMC from controls. Cultured CADASIL VSMCs were not more vulnerable than control cells to a number of toxic substances. Morphological studies showed reduced mitochondrial connectivity and increased number of mitochondria in CADASIL VSMCs. Transmission electron microscopy analysis demonstrated increased irregular and abnormal mitochondria in CADASIL VSMCs. Measurements of mitochondrial membrane potential (Δψ{sub m}) showed a lower percentage of fully functional mitochondria in CADASIL VSMCs. For a number of genes previously reported to be changed in CADASIL VSMCs, immunoblotting analysis demonstrated a significantly reduced SOD1 expression. These findings suggest that alteration of proliferation and mitochondrial function in CADASIL VSMCs might have an effect on vital cellular functions important for CADASIL pathology. -- Highlights: ► CADASIL is an inherited disease of cerebral vascular cells. ► Mitochondrial dysfunction has been implicated in the pathogenesis of CADASIL. ► Lower proliferation rates in CADASIL VSMC. ► Increased irregular and abnormal mitochondria and lower mitochondrial membrane potential in CADASIL VSMCs. ► Reduced mitochondrial connectivity and increased number of mitochondria in CADASIL VSMCs.

  3. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess

    PubMed Central

    Wyrwoll, Caitlin S.; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R.; Rog-Zielinska, Eva A.; Moran, Carmel M.; Seckl, Jonathan R.; Chapman, Karen E.; Holmes, Megan C.

    2016-01-01

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2−/− mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2+/+, Hsd11b2+/−, and Hsd11b2−/− littermates from heterozygous (Hsd11b+/−) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2−/− fetuses did not undergo the normal gestational increase seen in Hsd11b2+/+ littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2−/− fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2−/− fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2−/− fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction. PMID:27185937

  4. Vascularized tissue-engineered chambers promote survival and function of transplanted islets and improve glycemic control.

    PubMed

    Knight, K R; Uda, Y; Findlay, M W; Brown, D L; Cronin, K J; Jamieson, E; Tai, T; Keramidaris, E; Penington, A J; Rophael, J; Harrison, L C; Morrison, W A

    2006-03-01

    We have developed a chamber model of islet engraftment that optimizes islet survival by rapidly restoring islet-extracellular matrix relationships and vascularization. Our aim was to assess the ability of syngeneic adult islets seeded into blood vessel-containing chambers to correct streptozotocin-induced diabetes in mice. Approximately 350 syngeneic islets suspended in Matrigel extracellular matrix were inserted into chambers based on either the splenic or groin (epigastric) vascular beds, or, in the standard approach, injected under the renal capsule. Blood glucose was monitored weekly for 7 weeks, and an intraperitoneal glucose tolerance test performed at 6 weeks in the presence of the islet grafts. Relative to untreated diabetic animals, glycemic control significantly improved in all islet transplant groups, strongly correlating with islet counts in the graft (P<0.01), and with best results in the splenic chamber group. Glycemic control deteriorated after chambers were surgically removed at week 8. Immunohistochemistry revealed islets with abundant insulin content in grafts from all groups, but with significantly more islets in splenic chamber grafts than the other treatment groups (P<0.05). It is concluded that hyperglycemia in experimental type 1 diabetes can be effectively treated by islets seeded into a vascularized chamber functioning as a "pancreatic organoid."

  5. Maintenance of vascular integrity by pericytes is essential for normal kidney function.

    PubMed

    Lemos, Dario R; Marsh, Graham; Huang, Angela; Campanholle, Gabriela; Aburatani, Takahide; Dang, Lan; Gomez, Ivan; Fisher, Ken; Ligresti, Giovanni; Peti-Peterdi, Janos; Duffield, Jeremy S

    2016-12-01

    Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1(+) mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice. Loss of pericytes led to a rapid accumulation of neutral lipid vacuoles, swollen mitochondria, and apoptosis in tubular epithelial cells. Pericyte ablation led to endothelial cell swelling, reduced expression of vascular homeostasis markers, and peritubular capillary loss. Despite the observed injury, no signs of the acute inflammatory response were observed. Pathway enrichment analysis of genes expressed in kidney pericytes in vivo identified basement membrane proteins, angiogenic factors, and factors regulating vascular tone as major regulators of vascular function. Using novel microphysiological devices, we recapitulated human kidney peritubular capillaries coated with pericytes and showed that pericytes regulate permeability, basement membrane deposition, and microvascular tone. These findings suggest that through the active support of the microvasculature, pericytes are essential to adult kidney homeostasis.

  6. Experimental studies of mitochondrial function in CADASIL vascular smooth muscle cells.

    PubMed

    Viitanen, Matti; Sundström, Erik; Baumann, Marc; Poyhonen, Minna; Tikka, Saara; Behbahani, Homira

    2013-02-01

    Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a familiar fatal progressive degenerative disorder characterized by cognitive decline, and recurrent stroke in young adults. Pathological features include a dramatic reduction of brain vascular smooth muscle cells and severe arteriopathy with the presence of granular osmophilic material in the arterial walls. Here we have investigated the cellular and mitochondrial function in vascular smooth muscle cell lines (VSMCs) established from CADASIL mutation carriers (R133C) and healthy controls. We found significantly lower proliferation rates in CADASIL VSMC as compared to VSMC from controls. Cultured CADASIL VSMCs were not more vulnerable than control cells to a number of toxic substances. Morphological studies showed reduced mitochondrial connectivity and increased number of mitochondria in CADASIL VSMCs. Transmission electron microscopy analysis demonstrated increased irregular and abnormal mitochondria in CADASIL VSMCs. Measurements of mitochondrial membrane potential (Δψ(m)) showed a lower percentage of fully functional mitochondria in CADASIL VSMCs. For a number of genes previously reported to be changed in CADASIL VSMCs, immunoblotting analysis demonstrated a significantly reduced SOD1 expression. These findings suggest that alteration of proliferation and mitochondrial function in CADASIL VSMCs might have an effect on vital cellular functions important for CADASIL pathology.

  7. Comparative assessment of vascular function in autoimmune rheumatic diseases: considerations of prevention and treatment.

    PubMed

    Soltész, Pál; Kerekes, György; Dér, Henriett; Szücs, Gabriella; Szántó, Sándor; Kiss, Emese; Bodolay, Edit; Zeher, Margit; Timár, Orsolya; Szodoray, Péter; Szegedi, Gyula; Szekanecz, Zoltán

    2011-05-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as the role of systemic inflammation including cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. The characteristics of vasculopathies may significantly differ depending on the underlying disease. While classical accelerated atherosclerosis has been associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or spondyloarthropathies (SpA), obliterative vasculopathy may rather be characteristic for systemic sclerosis (SSc) or mixed connective tissue disease (MCTD). Antiphospholipid antibodies have been implicated in vasculopathies underlying SLE, antiphospholipid syndrome (APS), RA and MCTD. There is also heterogeneity with respect to inflammatory risk factors. Cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) and immune complexes are primarily involved in arthritides, such as RA, SpA, as well as in SLE. On the other hand, autoantibodies including anti-oxLDL anti-cardiolipin and anti-β2GPI are rather involved in SLE- and APS-associated vasculopathies. Regarding the non-invasive assessment of vascular function, endothelial dysfunction, overt atherosclerosis and vascular stiffness may be indicated by brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and aortic pulse-wave velocity (PWV), respectively. These abnormalities have been described in most inflammatory rheumatic diseases. While ccIMT and stiffness are relatively stable, FMD may be influenced by many confounding factors. In addition to traditional vasculoprotection, immunosuppressive agents including corticosteroids, traditional and biologic DMARDs may have significant vascular and metabolic

  8. Dissociation between neural and vascular responses to sympathetic stimulation : contribution of local adrenergic receptor function

    NASA Technical Reports Server (NTRS)

    Jacob, G.; Costa, F.; Shannon, J.; Robertson, D.; Biaggioni, I.

    2000-01-01

    Sympathetic activation produced by various stimuli, eg, mental stress or handgrip, evokes regional vascular responses that are often nonhomogeneous. This phenomenon is believed to be the consequence of the recruitment of differential central neural pathways or of a sympathetically mediated vasodilation. The purpose of this study was to determine whether a similar heterogeneous response occurs with cold pressor stimulation and to test the hypothesis that local differences in adrenergic receptor function could be in part responsible for this diversity. In 8 healthy subjects, local norepinephrine spillover and blood flow were measured in arms and legs at baseline and during sympathetic stimulation induced by baroreflex mechanisms (nitroprusside infusion) or cold pressor stimulation. At baseline, legs had higher vascular resistance (27+/-5 versus 17+/-2 U, P=0.05) despite lower norepinephrine spillover (0.28+/-0.04 versus 0.4+/-0.05 mg. min(-1). dL(-1), P=0.03). Norepinephrine spillover increased similarly in both arms and legs during nitroprusside infusion and cold pressor stimulation. On the other hand, during cold stimulation, vascular resistance increased in arms but not in legs (20+/-9% versus -7+/-4%, P=0.03). Increasing doses of isoproterenol and phenylephrine were infused intra-arterially in arms and legs to estimate beta-mediated vasodilation and alpha-induced vasoconstriction, respectively. beta-Mediated vasodilation was significantly lower in legs compared with arms. Thus, we report a dissociation between norepinephrine spillover and vascular responses to cold stress in lower limbs characterized by a paradoxical decrease in local resistance despite increases in sympathetic activity. The differences observed in adrenergic receptor responses cannot explain this phenomenon.

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

    PubMed Central

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

    2016-01-01

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

  10. Diverse functional roles of monosaccharide transporters and their homologs in vascular plants: a physiological perspective.

    PubMed

    Slewinski, Thomas L

    2011-07-01

    Vascular plants contain two gene families that encode monosaccharide transporter proteins. The classical monosaccharide transporter(-like) gene superfamily is large and functionally diverse, while the recently identified SWEET transporter family is smaller and, thus far, only found to transport glucose. These transporters play essential roles at many levels, ranging from organelles to the whole plant. Many family members are essential for cellular homeostasis and reproductive success. Although most transporters do not directly participate in long-distance transport, their indirect roles greatly impact carbon allocation and transport flux to the heterotrophic tissues of the plant. Functional characterization of some members from both gene families has revealed their diverse roles in carbohydrate partitioning, phloem function, resource allocation, plant defense, and sugar signaling. This review highlights the broad impacts and implications of monosaccharide transport by describing some of the functional roles of the monosaccharide transporter(-like) superfamily and the SWEET transporter family.

  11. Effects of benidipine and candesartan on kidney and vascular function in hypertensive Dahl rats.

    PubMed

    Yao, Kozo; Sato, Hitoshi; Sonoda, Rie; Ina, Yasuhiro; Suzuki, Kazuo; Ohno, Tetsuji

    2003-07-01

    We examined the effect of the dihydropyridine calcium channel blocker (CCB) benidipine, the angiotensin II type 1 receptor blocker (ARB) candesartan, and the combination of these drugs on blood pressure and kidney and vascular function in rats with salt-induced hypertension. Dahl salt-sensitive (DS) rats were fed with a high-salt (8% NaCl) diet from 7 weeks of age. Benidipine (1, 3 mg/kg), candesartan (1, 3 mg/kg), benidipine (3 mg/kg) combined with candesartan (3 mg/kg), or vehicle was administered orally after the start of the feeding. Relaxant responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) were measured to examine the vascular function. DS rats fed the high-salt diet showed an increase in systolic blood pressure (SBP), which was accompanied by glomerular sclerosis and an increase in urinary albumin excretion. Relaxant responses to acetylcholine and sodium nitroprusside were impaired in superior mesenteric arterial rings from the hypertensive DS rats. SBP was significantly lower in all of the drug-treated groups than in the vehicle-treated group. The antihypertensive effect of benidipine at 3 mg/kg was more potent than that of candesartan at 3 mg/kg. The albuminuria was significantly decreased in the benidipine and benidipine plus candesartan groups, but not in the candesartan group. The level of SBP in the benidipine plus candesartan group was lower than that by either drug alone. In addition, benidipine alone and benidipine plus candesartan inhibited the glomerular sclerosis and the impairment of relaxant responses in the arteries. These results demonstrate that benidipine is more effective than candesartan in lowering blood pressure and preventing the impairment of kidney and vascular function in salt-sensitive hypertensive rats. In addition, the results suggest that combination therapy with benidipine and an ARB decreases blood pressure more effectively than either drug alone

  12. Functional Mineralocorticoid Receptors in Human Vascular Endothelial Cells Regulate ICAM-1 Expression and Promote Leukocyte Adhesion

    PubMed Central

    Caprio, Massimiliano; Newfell, Brenna G.; la Sala, Andrea; Baur, Wendy; Fabbri, Andrea; Rosano, Giuseppe; Mendelsohn, Michael E.; Jaffe, Iris Z.

    2008-01-01

    In clinical trials, aldosterone antagonists decrease cardiovascular mortality and ischemia by unknown mechanisms. The steroid hormone aldosterone acts by binding to the mineralocorticoid receptor (MR), a ligand-activated transcription factor. In humans, aldosterone causes MR-dependent endothelial cell (EC) dysfunction and in animal models, aldosterone increases vascular macrophage infiltration and atherosclerosis. MR antagonists inhibit these effects without changing blood pressure, suggesting a direct role for vascular MR in EC function and atherosclerosis. Whether human vascular EC express functional MR is not known. Here we show that human coronary artery and aortic EC express MR mRNA and protein and that EC MR mediates aldosterone-dependent gene transcription. Human EC also express the enzyme 11-beta hydroxysteroid dehydrogenase-2(11βHSD2) and inhibition of 11βHSD2 in aortic EC enhances gene transactivation by cortisol, supporting that EC 11βHSD2 is functional. Furthermore, aldosterone stimulates transcription of the proatherogenic leukocyte-EC adhesion molecule Intercellular Adhesion Molecule-1(ICAM1) gene and protein expression on human coronary artery EC, an effect inhibited by the MR antagonist spironolactone and by MR knock-down with siRNA. Cell adhesion assays demonstrate that aldosterone promotes leukocyte-EC adhesion, an effect that is inhibited by spironolactone and ICAM1 blocking antibody, supporting that aldosterone induction of EC ICAM1 surface expression via MR mediates leukocyte-EC adhesion. These data show that aldosterone activates endogenous EC MR and proatherogenic gene expression in clinically important human EC. These studies describe a novel mechanism by which aldosterone may influence ischemic cardiovascular events and support a new explanation for the decrease in ischemic events in patients treated with aldosterone antagonists. PMID:18467630

  13. [The structural and functional neurovisualization in patients with epileptic seizures in cerebro-vascular diseases].

    PubMed

    Bazilevich, S N; Odinak, M M; Dyskin, D E; Krasakov, I V; Fokin, V A; P'ianov, I V; Dekan, V S; Okol'zin, A V; Pozdniakov, A V; Stanzhevskiĭ, A A

    2008-01-01

    The results of the dynamic study of patients with epileptic seizures in chronic and acute cerebral vascular pathology are presented. Various methods of structural and functional neurovisualization--magnetic resonance tomography using perfusion- and diffusion-weighted imaging, proton magnetic resonance spectroscopy, positron emission tomography, single photon emission computed tomography were used. Based on the results obtained in the study, the authors discuss etiopathogenetic variants of the development of these seizures and new possible approaches to the complex treatment besides the administration of antiepileptic medications.

  14. Do bryophyte shoot systems function like vascular plant leaves or canopies? Functional trait relationships in Sphagnum mosses (Sphagnaceae).

    PubMed

    Rice, Steven K; Aclander, Lynn; Hanson, David T

    2008-11-01

    Vascular plant leaf traits that influence photosynthetic function form the basis of mechanistic models of carbon exchange. Given their unique tissue organization, bryophytes may not express similar patterns. We investigated relationships among tissue, shoot, and canopy traits, and their associations with photosynthetic characteristics in 10 Sphagnum species. Trait relationships were organized around a primary dimension accounting for 43% of variation in 12 traits. There was no significant relationship between nitrogen content of shoot systems and maximum photosynthesis expressed on mass (A(mass)) or area (A(area)) bases due to nitrogen sequestration and storage within the canopy interior. This pattern differs from the distribution of nitrogen in vascular plant canopies. Thus, nitrogen and its relationship to carbon uptake in Sphagnum shoots does not conform to patterns of either vascular plant leaves or canopies. Species that concentrate biomass and nitrogen in the capitulum have enhanced rates of A(mass) and A(area). Consequently, A(area) was positively associated with N(area) of the capitulum only. Overall, water content and carotenoid concentration were the strongest predictors of both A(mass) and A(area) and these were expressed as inverse relationships. The relationships of plant traits in Sphagnum defines a principal trade-off between species that tolerate environmental stress and those that maximize carbon assimilation.

  15. Identification of Chemical Vascular Disruptors During Development Using An Integrative Predictive Toxicity Model and Zebrafish and in Vitro Functional Angiogenesis Assays.

    EPA Science Inventory

    Identification of chemical vascular disruptors during development using an integrative predictive toxicity model and zebrafish and in vitro functional angiogenesis assays Chemically-induced vascular toxicity during embryonic development can result in a wide range of adverse pre...

  16. How Does Maternal Employment Affect Children's Socioemotional Functioning?

    ERIC Educational Resources Information Center

    Lam, Gigi

    2015-01-01

    The maternal employment becomes an irreversible trend across the globe. The effect of maternal employment on children's socioemotional functioning is so pervasive that it warrants special attention to investigate into the issue. A trajectory of analytical framework of how maternal employment affects children's socioemotional functioning originates…

  17. Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure

    PubMed Central

    Kothiya, Milankumar; Galvani, Sylvain; Obinata, Hideru; Bucci, Mariarosaria; Giordano, Frank J; Jiang, Xian-Cheng; Hla, Timothy; Di Lorenzo, Annarita

    2015-01-01

    Endothelial dysfunction is a critical factor in many cardiovascular diseases, including hypertension. Although lipid signaling has been implicated in endothelial dysfunction and cardiovascular disease, specific molecular mechanisms are poorly understood. Here we report that Nogo-B, a membrane protein of the endoplasmic reticulum, regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Nogo-B inhibits serine palmitoyltransferase, the rate-limiting enzyme of the de novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine 1-phosphate and autocrine, G protein–coupled receptor–dependent signaling by this metabolite. Mice lacking Nogo-B either systemically or specifically in endothelial cells are hypotensive, resistant to angiotensin II–induced hypertension and have preserved endothelial function and nitric oxide release. In mice that lack Nogo-B, pharmacological inhibition of serine palmitoyltransferase with myriocin reinstates endothelial dysfunction and angiotensin II–induced hypertension. Our study identifies Nogo-B as a key inhibitor of local sphingolipid synthesis and shows that autocrine sphingolipid signaling within the endothelium is critical for vascular function and blood pressure homeostasis. PMID:26301690

  18. Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women.

    PubMed

    Akazawa, Nobuhiko; Choi, Youngju; Miyaki, Asako; Tanabe, Yoko; Sugawara, Jun; Ajisaka, Ryuichi; Maeda, Seiji

    2012-10-01

    Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function.

  19. Folic Acid Supplementation Improves Vascular Function in Professional Dancers With Endothelial Dysfunction

    PubMed Central

    Hoch, Anne Z.; Papanek, Paula; Szabo, Aniko; Widlansky, Michael E.; Gutterman, David D.

    2012-01-01

    Objective To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design Prospective cross-sectional study. Setting Academic institution in the Midwestern United States. Subjects Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flow-induced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. Results Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). Conclusions This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention. PMID:21715240

  20. Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth.

    PubMed

    Madeja, Zofia; Yadi, Hakim; Apps, Richard; Boulenouar, Selma; Roper, Stephen J; Gardner, Lucy; Moffett, Ashley; Colucci, Francesco; Hemberger, Myriam

    2011-03-08

    The mammalian fetus represents a semiallograft within the maternal uterus yet is not rejected. This situation is particularly pronounced in species with a hemochorial type of placentation, such as humans and rodents, where maternal tissues and blood are in direct contact with fetal trophoblast and thus potentially with paternal antigens. The main polymorphic antigens responsible for graft rejection are MHC antigens. In humans the trophoblast cells invading into the decidua have a unique pattern of MHC class I expression characterized by both classical (HLA-C) and nonclassical (HLA-G and HLA-E) molecules. Whether such an unusual MHC repertoire on the surface of trophoblast is a conserved feature between species with hemochorial placentation has not been resolved. Here we demonstrate, using a range of methods, that C57BL/6 mouse trophoblast predominantly expresses only one MHC class I antigen, H2-K, at the cell surface of giant cells but lacks expression of nonclassical MHC molecules. Antigenic disparity between parental MHCs affects trophoblast-induced transformation of the uterine vasculature and, consequently, placental and fetal gowth. Maternal uterine blood vessels were more dilated, allowing for increased blood supply, in certain combinations of maternal and paternal MHC haplotypes, and these allogeneic fetuses and placentas were heavier at term compared with syngeneic controls. Thus, maternal-fetal immune interactions are instrumental to optimize reproductive success. This cross-talk has important implications for human disorders of pregnancy, such as preeclampsia and fetal growth restriction.

  1. Vascular filtration function in galactose-fed versus diabetic rats: The role of polyol pathway activity

    SciTech Connect

    Pugliese, G.; Tilton, R.G.; Speedy, A.; Chang, K.; Province, M.A.; Kilo, C.; Williamson, J.R. )

    1990-07-01

    These studies were undertaken to assess the effects of increased galactose (v increased glucose) metabolism via the polyol pathway on vascular filtration function in the kidneys, eyes, nerves, and aorta. Quantitative radiolabeled tracer techniques were used to assess glomerular filtration rate (GFR) and regional tissue vascular clearance of plasma 131I-bovine serum albumin (BSA) in five groups of male Sprague-Dawley rats: nondiabetic controls, streptozotocin-diabetic rats, nondiabetic rats fed a 50% galactose diet, diabetic rats treated with sorbinil (an aldose reductase inhibitor), and galactose-fed rats treated with sorbinil. Sorbinil was added to the diet to provide a daily dose of approximately .2 mmol/kg body weight. After 2 months of diabetes or galactose ingestion, albumin clearance was increased twofold to fourfold in the eye (anterior uvea, choroid, and retina), sciatic nerve, aorta, and kidney; GFR was increased approximately twofold and urinary excretion of endogenous albumin and IgG were increased approximately 10-fold. Sorbinil treatment markedly reduced or completely prevented all of these changes in galactose-fed, as well as in diabetic rats. These observations support the hypothesis that increased metabolism of glucose via the sorbitol pathway is of central importance in mediating virtually all of the early changes in vascular filtration function associated with diabetes in the kidney, as well as in the eyes, nerves, and aorta. On the other hand, renal hypertrophy in diabetic rats and polyuria, hyperphagia, and impaired weight gain in galactose-fed and in diabetic rats were unaffected by sorbinil and therefore are unlikely to be mediated by increased polyol metabolism.

  2. Uteroplacental insufficiency and lactational environment separately influence arterial stiffness and vascular function in adult male rats.

    PubMed

    Tare, Marianne; Parkington, Helena C; Bubb, Kristen J; Wlodek, Mary E

    2012-08-01

    Early life environmental influences can have lifelong consequences for health, including the risk of cardiovascular disease. Uteroplacental insufficiency causes fetal undernutrition and impairs fetal growth. Previously we have shown that uteroplacental insufficiency is associated with impaired maternal mammary development, compromising postnatal growth leading to hypertension in male rat offspring. In this study we investigated the roles of prenatal and postnatal nutritional environments on endothelial and smooth muscle reactivity and passive wall stiffness of resistance arteries of male rat offspring. Fetal growth restriction was induced by maternal bilateral uterine vessel ligation (restricted) on day 18 of pregnancy. Control offspring were from mothers that had sham surgery (control) and another group from mothers with their litter size reduced (reduced; litter size reduced to 5 at birth, equivalent to the restricted group). On postnatal day 1, offspring (control, restricted, and reduced) were cross-fostered onto control or restricted mothers. At 6 months, mesenteric and femoral arteries were studied using wire and pressure myography. In restricted-on-restricted rats, wall stiffness was increased, and sensitivity to phenylephrine and relaxation evoked by endothelium-derived hyperpolarizing factor and sodium nitroprusside were impaired in mesenteric arteries. In femoral arteries, relaxation to sodium nitroprusside was reduced, whereas wall stiffness was unaltered. Cross-fostering restricted offspring onto control mothers alleviated deficits in vascular stiffness and reactivity. Control or reduced offspring who suckled a restricted mother had marked vascular stiffening. In conclusion, prenatal and early postnatal environments separately influence vascular function and stiffness. Furthermore, the early postnatal lactational environment is a determinant of later cardiovascular function.

  3. Arterial structure and function in vascular ageing: are you as old as your arteries?

    PubMed

    Thijssen, Dick H J; Carter, Sophie E; Green, Daniel J

    2016-04-15

    Advancing age may be the most potent independent predictor of future cardiovascular events, a relationship that is not fully explained by time-related changes in traditional cardiovascular risk factors. Since some arteries exhibit differential susceptibility to atherosclerosis, generalisations regarding the impact of ageing in humans may be overly simplistic, whereas in vivo assessment of arterial function and health provide direct insight. Coronary and peripheral (conduit, resistance and skin) arteries demonstrate a gradual, age-related impairment in vascular function that is likely to be related to a reduction in endothelium-derived nitric oxide bioavailability and/or increased production of vasoconstrictors (e.g. endothelin-1). Increased exposure and impaired ability for defence mechanisms to resist oxidative stress and inflammation, but also cellular senescence processes, may contribute to age-related changes in vascular function and health. Arteries also undergo structural changes as they age. Gradual thickening of the arterial wall, changes in wall content (i.e. less elastin, advanced glycation end-products) and increase in conduit artery diameter are observed with older age and occur similarly in central and peripheral arteries. These changes in structure have important interactive effects on artery function, with increases in small and large arterial stiffness representing a characteristic change with older age. Importantly, direct measures of arterial function and structure predict future cardiovascular events, independent of age or other cardiovascular risk factors. Taken together, and given the differential susceptibility of arteries to atherosclerosis in humans, direct measurement of arterial function and health may help to distinguish between biological and chronological age-related change in arterial health in humans.

  4. Vascular flows and transpiration affect peach (Prunus persica Batsch.) fruit daily growth.

    PubMed

    Morandi, Brunella; Rieger, Mark; Grappadelli, Luca Corelli

    2007-01-01

    The relative contributions of xylem, phloem, and transpiration to fruit growth and the daily patterns of their flows have been determined in peach, during the two stages of rapid diameter increase, by precise and continuous monitoring of fruit diameter variations. Xylem, phloem, and transpiration contributions to growth were quantified by comparing the diurnal patterns of diameter change of fruits, which were then girdled and subsequently detached. Xylem supports peach growth by 70%, and phloem 30%, while transpiration accounts for approximately 60% of daily total inflows. These figures and their diurnal patterns were comparable among years, stages, and cultivars. Xylem was functional at both stage I and III, while fruit transpiration was high and strictly dependent on environmental conditions, causing periods of fruit shrinkage. Phloem imports were correlated to fruit shrinkage and appear to facilitate subsequent fruit enlargement. Peach displays a growth mechanism which can be explained on the basis of passive unloading of photoassimilates from the phloem. A pivotal role is played by the large amount of water flowing from the tree to the fruit and from the fruit to the atmosphere.

  5. The Effect of Exercise on Vascular Function and Stiffness in Type 2 Diabetes: A Systematic Review and Meta-analysis.

    PubMed

    Way, Kimberley Larisa; Keating, Shelley Elizabeth; Baker, Michael Kevin; Chuter, Vivienne Helaine; Johnson, Nathan Anthony

    2016-01-01

    Deterioration of the structure and function of the vascular system is the underlying feature in cardiovascular disease (CVD), which is the highest cause of mortality in type 2 diabetes (T2D). Studies assessing the effect of exercise on vascular function and stiffness have used different measurement techniques and small cohorts, making it difficult to conclude on the overall efficacy of exercise on these outcomes. The aim of this study was to assess the effect of exercise on vascular function and stiffness in T2D. Electronic database searches were performed in AMED, MEDLINE, MEDLINE Daily Update, PREMEDLINE, SPORTDiscus, CINAHL, EMBASE and Web of Science. The effect size (ES), and 95% confidence intervals (CIs) of eligible studies were calculated. Pooled estimates of the effect of aerobic exercise (AEx) on vascular function and stiffness, using ES, were obtained. Results show that AEx led to a near-significant reduction in PWV (ES = -0.472; 95% CI: -0.949 to 0.005; P = 0.052), a significant reduction in EID (ES = 0.416, 95% CI: 0.062 to 0.769; P= 0.021), and a non-significant benefit in FMD measures. There were limited studies using resistance training or in combination with aerobic exercise, to assess a pooled effect on vascular function or stiffness. These data suggest that aerobic exercise training should be used as a primary treatment strategy for improving vascular smooth muscle function as measured by EID in individuals with T2D. There is currently insufficient evidence concerning the efficacy of regular exercise for improving vascular function and stiffness as measured by FMD and PWV.

  6. Polydopamine-mediated immobilization of multiple bioactive molecules for the development of functional vascular graft materials.

    PubMed

    Lee, Yu Bin; Shin, Young Min; Lee, Ji-Hye; Jun, Indong; Kang, Jae Kyeong; Park, Jong-Chul; Shin, Heungsoo

    2012-11-01

    In this study, we introduced a simple method for polydopamine-mediated immobilization of dual bioactive factors for the preparation of functionalized vascular graft materials. Polydopamine was deposited on elastic and biodegradable poly(lactic acid-co-ɛ-caprolactone) (PLCL) films, and a cell adhesive RGD-containing peptide and basic fibroblast growth factor were subsequently immobilized by simple dipping. We used an enzyme-linked immunosorbent assay and fluorescamine assay to confirm that we had stably immobilized bioactive molecules on the polydopamine-coated PLCL film in a reaction time-dependent manner. When human umbilical vein endothelial cells (HUVEC) were cultured on the prepared substrates, the number of adherent cells and proliferation of HUVEC for up to 14 days were greatest on the film immobilized with dual factors. On the other hand, the film immobilized with RGD peptide exhibited the highest migration speed compared to the other groups. The expression of cluster of differentiation 31 and von Willebrand factor, which indicates maturation of endothelial cells, was highly stimulated in the dual factor-immobilized group, and passively adsorbed factors showed a negligible effect. The immobilization of bioactive molecules inspired by polydopamine was successful, and adhesion, migration, proliferation and differentiation of HUVEC were synergistically accelerated by the presence of multiple signaling factors. Collectively, our results have demonstrated that a simple coating with polydopamine enables the immobilization of multiple bioactive molecules for preparation of polymeric functionalized vascular graft materials.

  7. Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function

    NASA Technical Reports Server (NTRS)

    Meck, Janice V.; Martin, David S.; D'Aunno, Dominick S.; Waters, Wendy W.

    2003-01-01

    Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

  8. Production of functional human vascular endothelial growth factor(165) in transgenic rice cell suspension cultures.

    PubMed

    Chung, Nguyen-Duc; Kim, Nan-Sun; Giap, Do Van; Jang, Seon-Hui; Oh, Sun-Mi; Jang, Sun-Hee; Kim, Tae-Geum; Jang, Yong-Suk; Yang, Moon-Sik

    2014-09-01

    Vascular endothelial growth factors (VEGFs) are secreted by tumor cells and other cells exposed to hypoxia, and play a critical role in the development and differentiation of the vascular system. In this study, we investigated the production of functional recombinant human VEGF165 (rhVEGF165) in transgenic rice cell suspension culture. Complementary DNA was synthesized from human leukemia HL60 cells and cloned into expression vectors under the control of the rice α-amylase 3D (RAmy3D) promoter. The rice seed (Oryza sativa L. cv. Dongjin) was transformed with this recombinant vector by the Agrobacterium mediated method and the integration of the target gene into the plant genome was confirmed by genomic PCR. The expression of rhVEGF165 in the rice cells was determined by Northern blot and Western blot analyses. The accumulated rhVEGF165 protein in the culture medium was 19 mg/L after 18 days of culturing in a sugar-free medium. The rhVEGF165 was purified using a heparin HP column and its biological activity was tested on human umbilical vein endothelial cells (HUVECs). The purified rhVEGF165 significantly increased the proliferative activity of the HUVECs. Therefore, it was demonstrated that functional rhVEGF165 could be produced using transgenic rice suspension culture vector under the control of the RAmy3D promoter.

  9. The Development of Depressive Symptoms During Medical Internship Stress Predicts Worsening Vascular Function

    PubMed Central

    Fiedorowicz, Jess G.; Ellingrod, Vicki L.; Kaplan, Mariana J.; Sen, Srijan

    2015-01-01

    Objective We sought to prospectively determine whether the onset of internship stress and any subsequent depression alters physiological markers of early vascular disease Methods We explored potential mechanisms linking stress and depression to vascular disease in a prospective cohort of 37 participants exposed to medical internship stress, an established precipitant of depressive symptomatology. Results Change in depressive symptom score from baseline over one year of internship stress was inversely correlated with change in the reactive hyperemia index (RHI), a measure of peripheral endothelial function (r=0.41, p=0.01). The change in depressive symptoms in the first six months of internship was similarly related to change in RHI over one year (r=0.38, p=0.02). While the development of depressive symptoms did not significantly impact changes in endothelial progenitor cells (EPCs), EPCs did significantly decrease with the year of internship stress (11.9 to 3.4 cells/ml blood; p=0.01). Conclusion Endothelial function may be a critical link between stress, depression, and cardiovascular disease and a feasible surrogate outcome for prospective studies. PMID:26115588

  10. Exercise training improves vascular function in adolescents with type 2 diabetes.

    PubMed

    Naylor, Louise H; Davis, Elizabeth A; Kalic, Rachelle J; Paramalingam, Niru; Abraham, Mary B; Jones, Timothy W; Green, Daniel J

    2016-02-01

    The impact of exercise training on vascular health in adolescents with type 2 diabetes has not been previously studied. We hypothesized that exercise training would improve micro- and macrovascular health in adolescents with type 2 diabetes. Thirteen adolescents (13-21 years, 10F) with type 2 diabetes were recruited from Princess Margaret Hospital. Participants were randomized to receive either an exercise program along with standard clinical care (n = 8) or standard care alone (n = 5). Those in the intervention group received 12 weeks of gym-based, personalized, and supervised exercise training. Those in the control group were instructed to maintain usual activity levels. Assessments were conducted at baseline and following week 12. The exercise group was also studied 12 weeks following the conclusion of their program. Assessments consisted of conduit artery endothelial function (flow-mediated dilation, FMD) and microvascular function (cutaneous laser Doppler). Secondary outcomes included body composition (dual-energy X-ray absorptiometry, DXA), glycemic control (whole body insulin sensitivity, M) assessed using the euglycemic-hyperinsulinemic clamp protocol, cardiorespiratory fitness (V˙O2peak), and muscular strength (1RM). Exercise training increased FMD (P < 0.05), microvascular function (P < 0.05), total lean mass (P < 0.05), and muscle strength (P < 0.001). There were no changes in cardiorespiratory fitness, body weight, BMI, or M. In the control group, body weight (P < 0.01), BMI (P < 0.01), and total fat mass (P < 0.05) increased. At week 24, improvements in vascular function were reversed. This study indicates that exercise training can improve both conduit and microvascular endothelial function and health, independent of changes in insulin sensitivity in adolescents with type 2 diabetes.

  11. Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain.

    PubMed

    Olver, T Dylan; Ferguson, Brian S; Laughlin, M Harold

    2015-01-01

    Compared with resting conditions, during incremental exercise, cardiac output in humans is elevated from ~5 to 25 L min(-1). In conjunction with this increase, the proportion of cardiac output directed toward skeletal muscle increases from ~20% to 85%, while blood flow to cardiac muscle increases 500% and blood flow to specific brain structures increases nearly 200%. Based on existing evidence, researchers believe that blood flow in these tissues is matched to the increases in metabolic rate during exercise. This phenomenon, the matching of blood flow to metabolic requirement, is often referred to as functional hyperemia. This chapter summarizes mechanical and metabolic factors that regulate functional hyperemia as well as other exercise-induced signals, which are also potent stimuli for chronic adaptations in vascular biology. Repeated exposure to exercise-induced increases in shear stress and the induction of angiogenic factors alter vascular cell gene expression and mediate changes in vascular volume and blood flow control. The magnitude and regulation of this coordinated response appear to be tissue specific and coupled to other factors such as hypertrophy and hyperplasia. The cumulative effects of these adaptations contribute to increased exercise capacity, reduced relative challenge of a given submaximal exercise bout and ameliorated vascular outcomes in patient populations with pathological conditions. In the subsequent discussion, this chapter explores exercise as a regulator of vascular biology and summarizes the molecular mechanisms responsible for exercise training-induced changes in vascular structure and function in skeletal and cardiac muscle as well as the brain.

  12. Small-World Brain Network and Dynamic Functional Distribution in Patients with Subcortical Vascular Cognitive Impairment

    PubMed Central

    Yu, Yongqiang; Zhou, Xia; Wang, Haibao; Hu, Xiaopeng; Zhu, Xiaoqun; Xu, Liyan; Zhang, Chao; Sun, Zhongwu

    2015-01-01

    To investigate the topological properties of the functional connectivity and their relationships with cognition impairment in subcortical vascular cognitive impairment (SVCI) patients, resting-state fMRI and graph theory approaches were employed in 23 SVCI patients and 20 healthy controls. Functional connectivity between 90 brain regions was estimated using bivariate correlation analysis and thresholded to construct a set of undirected graphs. Moreover, all of them were subjected to a battery of cognitive assessment, and the correlations between graph metrics and cognitive performance were further analyzed. Our results are as follows: functional brain networks of both SVCI patients and controls showed small-world attributes over a range of thresholds(0.15≤sparsity≤0.40). However, global topological organization of the functional brain networks in SVCI was significantly disrupted, as indicated by reduced global and local efficiency, clustering coefficients and increased characteristic path lengths relative to normal subjects. The decreased activity areas in SVCI predominantly targeted in the frontal-temporal lobes, while subcortical regions showed increased topological properties, which are suspected to compensate for the inefficiency of the functional network. We also demonstrated that altered brain network properties in SVCI are closely correlated with general cognitive and praxis dysfunction. The disruption of whole-brain topological organization of the functional connectome provides insight into the functional changes in the human brain in SVCI. PMID:26132397

  13. Bilayered vascular graft derived from human induced pluripotent stem cells with biomimetic structure and function

    PubMed Central

    Nakayama, Karina H; Joshi, Prajakta A; Lai, Edwina S; Gujar, Prachi; Joubert, Lydia-M; Chen, Bertha; Huang, Ngan F

    2015-01-01

    Background: We developed an aligned bi-layered vascular graft derived from human induced pluripotent stem cells (iPSCs) that recapitulates the cellular composition, orientation, and anti-inflammatory function of blood vessels. Materials & methods: The luminal layer consisted of longitudinal-aligned nanofibrillar collagen containing primary endothelial cells (ECs) or iPSC-derived ECs (iPSC-ECs). The outer layer contained circumferentially oriented nanofibrillar collagen with primary smooth muscle cells (SMCs) or iPSC-derived SMCs(iPSC-SMCs). Results: On the aligned scaffolds, cells organized F-actin assembly within 8º from the direction of nanofibrils. When compared to randomly-oriented scaffolds, EC-seeded aligned scaffolds had significant reduced inflammatory response, based on adhesivity to monocytes. Conclusion: This study highlights the importance of anisotropic scaffolds in directing cell form and function, and has therapeutic significance as physiologically relevant blood vessels. PMID:26440211

  14. Functional Vascular Study in Hypertensive Subjects with Type 2 Diabetes Using Losartan or Amlodipine

    PubMed Central

    Pozzobon, Cesar Romaro; Gismondi, Ronaldo A. O. C.; Bedirian, Ricardo; Ladeira, Marcia Cristina; Neves, Mario Fritsch; Oigman, Wille

    2014-01-01

    Background Antihypertensive drugs are used to control blood pressure (BP) and reduce macro- and microvascular complications in hypertensive patients with diabetes. Objectives The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan. Methods Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine (5 mg/day) or losartan (100 mg/day). Patient evaluation included BP measurement, ambulatory BP monitoring, and assessment of vascular parameters using applanation tonometry, pulse wave velocity (PWV), and flow-mediated dilation (FMD) of the brachial artery. Results A total of 42 patients were evaluated (21 in each group), with a predominance of women (71%) in both groups. The mean age of the patients in both groups was similar (amlodipine group: 54.9 ± 4.5 years; losartan group: 54.0 ± 6.9 years), with no significant difference in the mean BP [amlodipine group: 145 ± 14 mmHg (systolic) and 84 ± 8 mmHg (diastolic); losartan group: 153 ± 19 mmHg (systolic) and 90 ± 9 mmHg (diastolic)]. The augmentation index (30% ± 9% and 36% ± 8%, p = 0.025) and augmentation pressure (16 ± 6 mmHg and 20 ± 8 mmHg, p = 0.045) were lower in the amlodipine group when compared with the losartan group. PWV and FMD were similar in both groups. Conclusions Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan. However, the use of losartan may be associated with independent vascular reactivity to the pressor effect. PMID:25014057

  15. Human Embryonic Stem Cell Derived Vascular Progenitor Cells Capable of Endothelial and Smooth Muscle Cell Function

    PubMed Central

    Hill, Katherine L; Obrtlikova, Petra; Alvarez, Diego F; King, Judy A; Keirstead, Susan A; Allred, Jeremy R; Kaufman, Dan S

    2010-01-01

    OBJECTIVE Previous studies have demonstrated development of endothelial cells (ECs) and smooth muscle cells (SMCs) as separate cell lineages derived from human embryonic stem cells (hESCs). We demonstrate CD34+ cells isolated from differentiated hESCs function as vascular progenitor cells capable of producing both ECs and SMCs. These studies better define the developmental origin and reveal the relationship between these two cell types, as well as provide a more complete biological characterization. MATERIALS AND METHODS hESCs are co-cultured on M2-10B4 stromal cells or Wnt1 expressing M2-10B4 for 13–15 days to generate a CD34+ cell population. These cells are isolated using a magnetic antibody separation kit and cultured on fibronectin coated dishes in EC medium. To induce SMC differentiation, culture medium is changed and a morphological and phenotypic change occurs within 24–48 hours. RESULTS CD34+ vascular progenitor cells give rise to ECs and SMCs. The two populations express respective cell specific transcripts and proteins, exhibit intracellular calcium in response to various agonists, and form robust tube-like structures when co-cultured in Matrigel. Human umbilical vein endothelial cells (HUVEC) cultured under SMC conditions do not exhibit a change in phenotype or genotype. Wnt1 overexpressing stromal cells produced an increased number of progenitor cells. CONCLUSIONS The ability to generate large numbers of ECs and SMCs from a single vascular progenitor cell population is promising for therapeutic use to treat a variety of diseased and ischemic conditions. The step-wise differentiation outlined here is an efficient, reproducible method with potential for large scale cultures suitable for clinical applications. PMID:20067819

  16. Ectopic expression of foxtail millet zip-like gene, SiPf40, in transgenic rice plants causes a pleiotropic phenotype affecting tillering, vascular distribution and root development.

    PubMed

    Luan, Yunxia; Wang, Baosheng; Zhao, Qian; Ao, Guangming; Yu, Jingjuan

    2010-12-01

    Plant architecture determines grain production in rice (Oryza sativa) and is affected by important agronomic traits such as tillering, plant height, and panicle morphology. Many key genes involved in controlling the initiation and outgrowth of axillary buds, the elongation of stems, and the architecture of inflorescences have been isolated and analyzed. Previous studies have shown that SiPf40, which was identified from a foxtail millet (Setaria italica) immature seed cDNA library, causes extra branches and tillers in SiPf40-transgenic tobacco and foxtail millet, respectively. To reconfirm its function, we generated transgenic rice plants overexpressing SiPf40 under the control of the ubiquitin promoter. SiPf40-overexpressing transgenic plants have a greater tillering number and a wider tiller angle than wild-type plants. Their root architecture is modified by the promotion of lateral root development, and the distribution of xylem and phloem in the vascular bundle is affected. Analysis of hormone levels showed that the ratios of indole-3-acetic acid/zeatin (IAA/ZR) and IAA/gibberellic acid (IAA/GA) decreased in SiPf40-transgenic plants compared with wild-type plants. These findings strongly suggest that SiPf40 plays an important role in plant architecture.

  17. Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions

    PubMed Central

    Cools, Roshan; Nakamura, Kae; Daw, Nathaniel D

    2011-01-01

    Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotonin—comprising both affective and activational ones, as well as a number of other functions not overtly related to either—can be seen as consequences of a single root mechanism. PMID:20736991

  18. Genetic Causation of Neointimal Hyperplasia in Hemodialysis Vascular Access Dysfunction

    PubMed Central

    Lee, Timmy; Wadehra, Davinder

    2014-01-01

    The major cause of hemodialysis vascular access failure is venous stenosis resulting from neointimal hyperplasia. Genetic factors have been shown to be associated with cardiovascular disease (CVD) and peripheral vascular disease (PVD) in the general population. Genetic factors may also play an important role in vascular access stenosis and development of neointimal hyperplasia by affecting pathways that lead to inflammation, endothelial function, oxidative stress, and vascular smooth muscle proliferation. This review will discuss the role of genetics in understanding neointimal hyperplasia development in hemodialysis vascular access dysfunction and other disease processes with similar neointimal hyperplasia development such coronary artery disease and peripheral vascular disease. PMID:21917012

  19. Excess Visceral Adipose Tissue Worsens the Vascular Endothelial Function in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Kurozumi, Akira; Okada, Yosuke; Arao, Tadashi; Tanaka, Yoshiya

    2016-01-01

    Objective Visceral fat obesity and metabolic syndrome correlate with atherosclerosis in part due to insulin resistance and various other factors. The aim of this study was to determine the relationship between vascular endothelial dysfunction and excess visceral adipose tissue (VAT) in Japanese patients with type 2 diabetes mellitus (T2DM). Methods In 71 T2DM patients, the reactive hyperemia index (RHI) was measured using an Endo-PAT 2000, and VAT and subcutaneous adipose tissue (SAT) were measured via CT. We also measured various metabolic markers, including high-molecular-weight adiponectin (HMW-AN). Results VAT correlated negatively with the natural logarithm of RHI (L_RHI), the primary endpoint (p=0.042, r=-0.242). L_RHI did not correlate with SAT, VAT/SAT, abdominal circumference, homeostasis model assessment for insulin resistance, urinary C-peptide reactivity, HMW-AN, or alanine amino transferase, the secondary endpoints. A linear multivariate analysis via the forced entry method using age, sex, VAT, and smoking history as independent variables and L_RHI as the dependent variable revealed a lack of any determinants of L_RHI. Conclusion Excess VAT worsens the vascular endothelial function, represented by RHI which was analyzed using Endo-PAT, in Japanese patients with T2DM. PMID:27803400

  20. Effect of lower limb exercise on forearm vascular function: contribution of nitric oxide.

    PubMed

    Green, Daniel; Cheetham, Craig; Mavaddat, Louise; Watts, Katie; Best, Matthew; Taylor, Roger; O'Driscoll, Gerard

    2002-09-01

    We examined vascular function in an inactive muscle bed, the forearm, during lower limb exercise and determined the contribution of endothelium-derived nitric oxide (NO) to the hyperemic response. Eight young males were randomized to participate in two studies, each consisting of two bouts of lower limb exercise, separated by a 30-min recovery. Peak forearm blood flow (PFBF) and mean blood flow (MFBF) were continuously recorded at baseline and during exercise using continuous high-resolution vascular ultrasound and Doppler flow velocity measurement. During one session, the brachial artery was cannulated to allow continuous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase. The alternate session was performed to control for possible effects of repeated exercise. At 60, 100, and 160 W, L-NMMA significantly decreased both PFBF and MFBF compared with the saline infusion. These results suggest that systemic production of NO occurs during exercise in resting vessel beds, which do not feed metabolically active tissue. This finding provides a plausible explanation for the antiatherogenic benefits of exercise.

  1. Digital thermal monitoring of vascular function: a novel tool to improve cardiovascular risk assessment.

    PubMed

    Gul, Khawar M; Ahmadi, Naser; Wang, Zhiying; Jamieson, Craig; Nasir, Khurram; Metcalfe, Ralph; Hecht, Harvey S; Hartley, Craig J; Naghavi, Morteza

    2009-05-01

    Digital thermal monitoring (DTM) of vascular function during cuff-occlusive reactive hyperemia relies on the premise that changes in fingertip temperature during and after an ischemic stimulus reflect changes in blood flow. To determine its utility in individuals with and without known coronary heart disease (CHD), 133 consecutive individuals (age 54 +/- 10 years, 50% male, 19 with known CHD) underwent DTM during and after 2 minutes of supra-systolic arm cuff inflation. Fingertip temperatures of the occluded and non-occluded fingertips were measured simultaneously. Post-cuff deflation temperature rebound (TR) was lower in the CHD patients and in those with an increased Framingham risk score (FRS) compared to the normal group. After adjustment for age, sex, and cardiac risk factors, TR was significantly lower in those with CHD compared to those without CHD (p < 0.05). This study demonstrates that vascular dysfunction measured by DTM is associated with CHD and an increased FRS, and could potentially be used to identify high-risk patients.

  2. VEGFR signaling during lymphatic vascular development: From progenitor cells to functional vessels.

    PubMed

    Secker, Genevieve A; Harvey, Natasha L

    2015-03-01

    Lymphatic vessels are an integral component of the cardiovascular system, serving important roles in fluid homeostasis, lipid absorption, and immune cell trafficking. Defining the mechanisms by which the lymphatic vasculature is constructed and remodeled into a functional vascular network not only provides answers to fascinating biological questions, but is fundamental to understanding how lymphatic vessel growth and development goes awry in human pathologies. While long recognized as dysfunctional in lymphedema and exploited as a route of tumor metastasis, recent work has highlighted important roles for lymphatic vessels in modulating immune responses, regulating salt-sensitive hypertension and important for lung inflation at birth. Substantial progress in our understanding of the signaling pathways important for development and morphogenesis of the lymphatic vasculature has been made in recent years. Here, we review advances in our knowledge of the best characterized of these signaling pathways, that involving the vascular endothelial growth factor (VEGF) family members VEGF-C and VEGF-D, together with their receptors VEGFR2 and VEGFR3. Recent work has defined multiple levels at which signal transduction by means of this key axis is regulated; these include control of ligand processing and bioavailability, modulation of receptor activation by interacting proteins, and regulation of receptor endocytosis and trafficking.

  3. Carbondioxide-Aided Angiography Decreases Contrast Volume and Preserves Kidney Function in Peripheral Vascular Interventions.

    PubMed

    Stegemann, Emilia; Tegtmeier, Catharina; Bimpong-Buta, Nana Yaw; Sansone, Roberto; Uhlenbruch, Mark; Richter, Andreas; Stegemann, Berthold; Roden, Michael; Westenfeld, Ralf; Kelm, Malte; Heiss, Christian

    2016-10-01

    Chronic kidney disease is a common comorbidity in patients with peripheral artery disease. We investigated the safety and efficacy of carbon dioxide (CO2) as supplemental contrast agent to decrease contrast volume during fluoroscopy-guided peripheral vascular procedures in routine angiological practice. We analyzed 191 consecutive interventions of the lower extremity in claudicants and critical limb ischemia (CLI) that were performed with iodinated contrast media (ICM) alone (n = 154) or with the aided or exclusive use of CO2 (n = 37). The technical success rate, total irradiation, and intervention time were not significantly different between ICM and CO2 No severe procedure-related complications occurred. The contrast volume was lower in CO2 than in ICM. Although kidney function, creatinine, and estimated glomerular filtration rate was lower in CO2 at baseline, the incidence of contrast-induced nephropathy was lower in CO2 compared to ICM. These data support CO2 as an alternative supplemental contrast agent that can be applied safely and efficiently to lower contrast volume during peripheral vascular interventions preventing kidney dysfunction even in patients with disease of the popliteal artery and below the knee and CLI.

  4. The Association of Long-Functioning Hemodialysis Vascular Access with Prevalence of Left Ventricular Hypertrophy in Kidney Transplant Recipients

    PubMed Central

    Kujawa-Szewieczek, Agata; Szotowska, Magdalena; Więcek, Andrzej

    2014-01-01

    Left ventricular hypertrophy (LVH) is frequently observed in chronic dialysis patients and is also highly prevalent in kidney transplant recipients. This study evaluates the impact of long-functioning hemodialysis vascular access on LVH in single center cohort of kidney transplant recipients. 162 patients at 8.7 ± 1.8 years after kidney transplantation were enrolled. Echocardiography, carotid ultrasound, and assessment of pulse wave velocity were performed. LVH was defined based on left ventricular mass (LVM) indexed for body surface area (BSA) and height2.7. There were 67 patients with and 95 without patent vascular access. Both study groups were comparable with respect to gender, age, duration of dialysis therapy, and time after transplantation, kidney graft function, and cardiovascular comorbidities. Patients with patent vascular access were characterized by significantly elevated LVM and significantly greater percentage of LVH, based on LVMI/BSA (66.7 versus 48.4%, P = 0.02). OR for LVH in patients with patent vascular access was 2.39 (1.19–4.76), P = 0.01. Regression analyses confirmed an independent contribution of patent vascular access to higher LVM and increased prevalence of LVH. We concluded that long-lasting patent hemodialysis vascular access after kidney transplantation is associated with the increased prevalence of LVH in kidney transplant recipients. PMID:24616896

  5. Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion

    PubMed Central

    Berens, Eric B.; Sharif, Ghada M.; Schmidt, Marcel O.; Yan, Gai; Shuptrine, Casey W.; Weiner, Louis M.; Glasgow, Eric; Riegel, Anna T.; Wellstein, Anton

    2016-01-01

    Cancer cell vascular invasion is a crucial step in the malignant progression towards metastasis. Here we used a genome-wide RNAi screen with E0771 mammary cancer cells to uncover drivers of endothelial monolayer invasion. We identified keratin-associated protein 5-5 (Krtap5-5) as a candidate. Krtap5-5 belongs to a large protein family that is implicated in crosslinking keratin intermediate filaments during hair formation, yet these keratin-associated proteins have no reported role in cancer. Depletion of Krtap5-5 from cancer cells led to cell blebbing and a loss of keratins 14 and 18, in addition to the upregulation of vimentin intermediate filaments. This intermediate filament subtype switching induced dysregulation of the actin cytoskeleton and reduced the expression of hemidesmosomal α6/β4-integrins. We further demonstrate that knockdown of keratin 18 phenocopies the loss of Krtap5-5, suggesting that Krtap5-5 crosstalks with keratin 18 in E0771 cells. Disruption of the keratin cytoskeleton by perturbing Krtap5-5 function broadly altered the expression of cytoskeleton regulators and the localization of cell surface markers. Krtap5-5 depletion did not impact cell viability but reduced cell motility and extracellular matrix invasion, as well as extravasation of cancer cells into tissues in zebrafish and mice. We conclude that Krtap5-5 is a previously unknown regulator of cytoskeletal function in cancer cells that modulates motility and vascular invasion. Thus, in addition to its physiologic function, a keratin-associated protein can serve as a switch towards malignant progression. PMID:27375028

  6. Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion

    PubMed Central

    Waked, Imam; Berhane, Sarah; Toyoda, Hidenori; Chan, Stephen L; Stern, Nicholas; Palmer, Daniel; Tada, Toshifumi; Yeo, Winnie; Mo, Frankie; Bettinger, Dominik; Kirstein, Martha M; Iñarrairaegui, Mercedes; Gomaa, Asmaa; Vogel, Arndt; Meyer, Tim; Sangro, Bruno; Lai, Paul; Kumada, Takashi; Johnson, Philip J

    2017-01-01

    Background: Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function and tumour-related factors to offer a simple prognostic scoring system. The Albumin-Bilirubin (ALBI) grade permits assessment of the impact of liver function on survival. We aimed to investigate these two models and vascular invasion (VI). Methods: In an international cohort of 3030 patients undergoing TACE, we examined the impact of liver function as assessed by the ALBI score, the HAP score and VI on survival. Results: Classification according to ALBI grade resulted in non-overlapping survival curves in the overall data set and all regional cohorts. The HAP score was also validated. Tumour number, aetiology and VI were identified as additional independent prognostic risk factors not currently included in the HAP score. Survival was particularly poor for patients with VI. Conclusions: The ALBI grade categorised patients receiving TACE into three clear prognostic groups, thereby emphasising the importance of underlying liver function in the outcome of TACE. The HAP score has been validated internationally and the serious adverse impact of VI is clearly shown. PMID:28125820

  7. Acute exercise improves endothelial function despite increasing vascular resistance during stress in smokers and nonsmokers.

    PubMed

    Rooks, Cherie R; McCully, Kevin K; Dishman, Rod K

    2011-09-01

    The present study examined the effect of acute exercise on flow mediated dilation (FMD) and reactivity to neurovascular challenges among female smokers and nonsmokers. FMD was determined by arterial diameter, velocity, and blood flow measured by Doppler ultrasonography after forearm occlusion. Those measures and blood pressure and heart rate were also assessed in response to forehead cold and the Stroop Color-Word Conflict Test (CWT) before and after 30 min of rest or an acute bout of cycling exercise (∼50% VO₂ peak). Baseline FMD and stress responses were not different between smokers and nonsmokers. Compared to passive rest, exercise increased FMD and decreased arterial velocity and blood flow responses during the Stroop CWT and forehead cold in both groups. Overall, acute exercise improved endothelial function among smokers and nonsmokers despite increasing vascular resistance and reducing limb blood flow during neurovascular stress.

  8. The oxidase activity of vascular adhesion protein-1 (VAP-1) is essential for function.

    PubMed

    Noonan, Thomas; Lukas, Susan; Peet, Gregory W; Pelletier, Josephine; Panzenbeck, Mark; Hanidu, Adedayo; Mazurek, Suzanne; Wasti, Ruby; Rybina, Irina; Roma, Teresa; Kronkaitis, Anthony; Shoultz, Alycia; Souza, Donald; Jiang, Huiping; Nabozny, Gerald; Modis, Louise Kelly

    2013-01-01

    Vascular adhesion protein-1 (VAP-1) has been implicated in the pathogenesis of inflammatory diseases and is suggested to play a role in immune cell trafficking. It is not clear whether this effect is mediated by the oxidase activity or by other features of the protein such as direct adhesion. In order to study the role of VAP-1 oxidase activity in vivo, we have generated mice carrying an oxidase activity-null VAP-1 protein. We demonstrate that the VAP-1 oxidase null mutant mice have a phenotype similar to the VAP-1 null mice in animal models of sterile peritonitis and antibody induced arthritis suggesting that the oxidase activity is responsible for the inflammatory function of VAP-1.

  9. The oxidase activity of vascular adhesion protein-1 (VAP-1) is essential for function

    PubMed Central

    Noonan, Thomas; Lukas, Susan; Peet, Gregory W; Pelletier, Josephine; Panzenbeck, Mark; Hanidu, Adedayo; Mazurek, Suzanne; Wasti, Ruby; Rybina, Irina; Roma, Teresa; Kronkaitis, Anthony; Shoultz, Alycia; Souza, Donald; Jiang, Huiping; Nabozny, Gerald; Modis, Louise Kelly

    2013-01-01

    Vascular adhesion protein-1 (VAP-1) has been implicated in the pathogenesis of inflammatory diseases and is suggested to play a role in immune cell trafficking. It is not clear whether this effect is mediated by the oxidase activity or by other features of the protein such as direct adhesion. In order to study the role of VAP-1 oxidase activity in vivo, we have generated mice carrying an oxidase activity-null VAP-1 protein. We demonstrate that the VAP-1 oxidase null mutant mice have a phenotype similar to the VAP-1 null mice in animal models of sterile peritonitis and antibody induced arthritis suggesting that the oxidase activity is responsible for the inflammatory function of VAP-1. PMID:23885334

  10. Functional role of stromal interaction molecule 1 (STIM1) in vascular smooth muscle cells

    SciTech Connect

    Takahashi, Yoichiro; Watanabe, Hiroyuki; Murakami, Manabu; Ono, Kyoichi; Munehisa, Yoshiko; Koyama, Takashi; Nobori, Kiyoshi; Iijima, Toshihiko; Ito, Hiroshi

    2007-10-05

    We investigated the functional role of STIM1, a Ca{sup 2+} sensor in the endoplasmic reticulum (ER) that regulates store-operated Ca{sup 2+} entry (SOCE), in vascular smooth muscle cells (VSMCs). STIM1 was mainly localized at the ER and plasma membrane. The knockdown of STIM1 expression by small interfering (si) RNA drastically decreased SOCE. In contrast, an EF-hand mutant of STIM1, STIM1{sup E87A}, produced a marked increase in SOCE, which was abolished by co-transfection with siRNA to transient receptor potential canonical 1 (TRPC1). In addition, transfection with siRNA against STIM1 suppressed phosphorylation of cAMP-responsive element binding protein (CREB) and cell growth. These results suggest that STIM1 is an essential component of SOCE and that it is involved in VSMC proliferation.

  11. Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats.

    PubMed

    Pugliese, G; Tilton, R G; Speedy, A; Chang, K; Santarelli, E; Province, M A; Eades, D; Sherman, W R; Williamson, J R

    1989-12-01

    Rats injected i.p. with a single dose of nicotinamide (250 mg/kg) 15 min prior to i.v. injection of streptozotocin (65 mg/kg) develop a very mild form of diabetes characterized by slight elevations of plasma glucose, increased levels of HbA1, and reduced insulin secretion in response to an i.v. glucose tolerance test. These rats gain weight normally and they are not hyperphagic, glycosuric, or polyuric. The effects of this very mild form of diabetes vs overt streptozotocin diabetes of three months duration on regional vascular 131I-albumin clearance, blood flow (assessed by 15 microns 85Sr-microspheres), and renal filtration function were examined in male Sprague-Dawley rats. Plasma glucose levels of rats with mild diabetes were 7.4 +/- 0.9 (mean +/- SD) (mmol/l) vs 6.5 +/- 0.6 for control rats and 31.3 +/- 6.0 for overtly diabetic rats. HbA1 levels were increased 1.4 fold in mildly diabetic and 2.3 fold in overtly diabetic rats. Vascular clearance of 131I-albumin was markedly increased in ocular tissues (anterior uvea, retina, and choroid), sciatic nerve, aorta, new (subcutaneous) granulation tissue, and kidney of both diabetic groups, although increases in overtly diabetic rats exceeded those in the mildly diabetic group (2.2-4.6 times control animals vs 1.6-3.3 times, respectively). Likewise, both overt and very mild diabetes markedly increased glomerular filtration rate (approximately 1.8 times and 1.2 times control animals, respectively), urinary excretion of endogenous albumin (approximately 9 times and 4 times) and IgG (approximately 15 times and 4 times), as well as regional blood flow in the anterior uvea, choroid, and sciatic nerve. Increases in tissue sorbitol levels were much larger in overtly diabetic rats (generally 10-20 times control animals) than in mildly diabetic rats (1.5-3 times controls). myo-Inositol levels were significantly decreased only in lens and sciatic nerve of overtly diabetic rats. These observations indicate that even very mild

  12. Treatment of denture-related stomatitis improves endothelial function assessed by flow-mediated vascular dilation

    PubMed Central

    Osmenda, Grzegorz; Maciąg, Joanna; Wilk, Grzegorz; Maciąg, Anna; Nowakowski, Daniel; Loster, Jolanta; Dembowska, Elżbieta; Robertson, Douglas; Guzik, Tomasz

    2016-01-01

    Introduction The presence of oral inflammation has recently been linked with the pathogenesis of cardiovascular diseases. While numerous studies have described links between periodontitis and endothelial dysfunction, little is known about the influence of denture-related stomatitis (DRS) on cardiovascular risk. Therefore, the aim of this study was to determine whether the treatment of DRS can lead to improvement of the clinical measures of vascular dysfunction. Material and methods The DRS patients were treated with a local oral antifungal agent for 3 weeks. Blood pressure, flow-mediated dilatation (FMD) and nitroglycerine-mediated vascular dilatation (NMD) were measured during three study visits: before treatment, one day and two months after conclusion of antifungal therapy. Results Flow-mediated dilatation measurements showed significant improvement of endothelial function 2 months after treatment (FMD median 5%, 95 CI: 3–8.3 vs. 11%, 95% CI: 8.8–14.4; p < 0.01), while there was no difference in control, endothelium-independent vasorelaxations (NMD; median = 15.3%, 95% CI: 10.8–19.3 vs. 12.7%, 95% CI: 10.6–15; p = 0.3). Other cardiovascular parameters such as systolic (median = 125 mm Hg; 95% CI: 116–129 vs. 120 mm Hg, 95% CI: 116–126; p = 0.1) as well as diastolic blood pressure and heart rate (median = 65.5 bpm, 95% CI: 56.7–77.7 vs. 71 bpm, 95% CI: 66.7–75; p = 0.5) did not change during or after the treatment. Conclusions Treatment of DRS is associated with improvement of endothelial function. Since endothelial dysfunction is known to precede the development of severe cardiovascular disorders such as atherosclerosis and hypertension, patients should be more carefully screened for DRS in general dental practice, and immediate DRS treatment should be advised. PMID:28144257

  13. Metabolic Profiling of Right Ventricular-Pulmonary Vascular Function Reveals Circulating Biomarkers of Pulmonary Hypertension

    PubMed Central

    Lewis, Gregory D.; Ngo, Debby; Hemnes, Anna R.; Farrell, Laurie; Domos, Carly; Pappagianopoulos, Paul P.; Dhakal, Bishnu P.; Souza, Amanda; Shi, Xu; Pugh, Meredith E.; Beloiartsev, Arkadi; Sinha, Sumita; Clish, Clary B.; Gerszten, Robert E.

    2016-01-01

    BACKGROUND Pulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements. OBJECTIVES This study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction. METHODS We measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30). RESULTS In the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [ΔPQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)–dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine–nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and ΔPQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension. CONCLUSIONS Metabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization. PMID

  14. Cavitation Resistance in Seedless Vascular Plants: The Structure and Function of Interconduit Pit Membranes.

    PubMed

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

    2014-06-01

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

  15. Primary vascular access.

    PubMed

    Gibbons, C P

    2006-05-01

    Primary vascular access is usually achievable by a distal autogenous arterio-venous fistula (AVF). This article describes the approach to vascular access planning, the usual surgical options and the factors affecting patency.

  16. The plant-specific dof transcription factors family: new players involved in vascular system development and functioning in Arabidopsis.

    PubMed

    Le Hir, Rozenn; Bellini, Catherine

    2013-01-01

    In higher plants phloem and xylem are responsible for long-distance transport of water, nutrients, and signals that act systemically at short or long-distance to coordinate developmental processes. The formation of the plant vascular system is a complex process that integrates signaling events and gene regulation at transcriptional and posttranscriptional levels. Thanks to transcriptomic and proteomic analysis we start to better understand the mechanisms underlying the formation and the functioning of the vascular system. The role of the DNA-binding with one finger (Dof TFs), a group of plant-specific transcription factors, recently emerged as part of the transcriptional regulatory networks acting on the formation and functioning of the vascular tissues. More than half of the members of this TF family are expressed in the vascular system. In addition some of them have been proposed to be mobile proteins, suggesting a possible role in the control of short- or long-distance signaling as well. This review summarizes the current knowledge on Dof TFs family in Arabidopsis with a special focus on their role in vascular development and functioning.

  17. Heat acclimation improves cutaneous vascular function and sweating in trained cyclists

    PubMed Central

    Lorenzo, Santiago

    2010-01-01

    The aim of this study was to explore heat acclimation effects on cutaneous vascular responses and sweating to local ACh infusions and local heating. We also sought to examine whether heat acclimation altered maximal skin blood flow. ACh (1, 10, and 100 mM) was infused in 20 highly trained cyclists via microdialysis before and after a 10-day heat acclimation program [two 45-min exercise bouts at 50% maximal O2 uptake (V̇o2max) in 40°C (n = 12)] or control conditions [two 45-min exercise bouts at 50% V̇o2max in 13°C (n = 8)]. Skin blood flow was monitored via laser-Doppler flowmetry (LDF), and cutaneous vascular conductance (CVC) was calculated as LDF ÷ mean arterial pressure. Sweat rate was measured by resistance hygrometry. Maximal brachial artery blood flow (forearm blood flow) was obtained by heating the contralateral forearm in a water spray device and measured by Doppler ultrasound. Heat acclimation increased %CVCmax responses to 1, 10, and 100 mM ACh (43.5 ± 3.4 vs. 52.6 ± 2.6% CVCmax, 67.7 ± 3.4 vs. 78.0 ± 3.0% CVCmax, and 81.0 ± 3.8 vs. 88.5 ± 1.1% CVCmax, respectively, all P < 0.05). Maximal forearm blood flow remained unchanged after heat acclimation (290.9 ± 12.7 vs. 269.9 ± 23.6 ml/min). The experimental group showed significant increases in sweating responses to 10 and 100 mM ACh (0.21 ± 0.03 vs. 0.31 ± 0.03 mg·cm−2·min−1 and 0.45 ± 0.05 vs. 0.67 ± 0.06 mg·cm−2·min−1, respectively, all P < 0.05), but not to 1 mM ACh (0.13 ± 0.02 vs. 0.18 ± 0.02 mg·cm−2·min−1, P = 0.147). No differences in any of the variables were found in the control group. Heat acclimation in highly trained subjects induced local adaptations within the skin microcirculation and sweat gland apparatus. Furthermore, maximal skin blood flow was not altered by heat acclimation, demonstrating that the observed changes were attributable to improvement in cutaneous vascular function and not to structural changes that limit maximal vasodilator capacity

  18. Isocyanate-functional adhesives for biomedical applications. Biocompatibility and feasibility study for vascular closure applications.

    PubMed

    Hadba, Ahmad R; Belcheva, Nadya; Jones, Fatima; Abuzaina, Ferass; Calabrese, Allison; Kapiamba, Mbiya; Skalla, Walter; Taylor, Jack L; Rodeheaver, George; Kennedy, John

    2011-10-01

    Biodegradable isocyanate-functional adhesives based on poly(ethylene glycol)-adipic acid esters were synthesized, characterized, and evaluated in vitro and in vivo. Two types of formulations, P2TT and P2MT, were developed by functionalization with 2,4-tolylene diisocyanate (TDI) or 4,4'-methylene-bis(phenyl isocyanate) (MDI), respectively, and branching with 1,1,1-trimethylolpropane (TMP). The biocompatibility of the synthesized adhesive formulations was evaluated as per ISO 10993. Cytotoxicity, systemic toxicity, pyrogenicity, genotoxicity (reverse mutation of Salmonella typhimurium and Escherichia coli), hemolysis, intracutaneous reactivity, and delayed-type hypersensitivity were evaluated. All formulations met the requirements of the conducted standard tests. The biological behavior and ability of the adhesive formulations to close an arteriotomy and withstand arterial pressure following partial approximation with a single suture were evaluated in a rat abdominal aorta model. Animals were evaluated at 1, 2, 3, and 4 weeks after surgery. Macroscopic and histopathologic evaluation of explanted arteries suggested that the P2TT formulation had better in vivo performance than the P2MT formulation. Additionally, the P2TT formulation resulted in less tissue reaction than P2MT formulation. To our knowledge, this is the first study demonstrating the potential of this new class of isocyanate-functional degradable adhesives for vascular applications.

  19. Effect of angiotensin-converting enzyme inhibitors on vascular endothelial function in hypertensive patients after intensive periodontal treatment.

    PubMed

    Rubio, María C; Lewin, Pablo G; De la Cruz, Griselda; Sarudiansky, Andrea N; Nieto, Mauricio; Costa, Osvaldo R; Nicolosi, Liliana N

    2016-04-01

    There is a relation between vascular endothelial function, atherosclerotic disease, and inflammation. Deterioration of endothelial function has been observed twenty-four hours after intensive periodontal treatment. This effect may be counteracted by the action of angiotensin-converting enzyme inhibitors, which improve endothelial function. The aim of the present study was to evaluate vascular endothelial function after intensive periodontal treatment, in hypertensive patients treated with angiotensinconverting enzyme inhibitors. A prospective, longitudinal, comparative study involving repeated measurements was conducted. Fifty-two consecutive patients with severe periodontal disease were divided into two groups, one comprising hypertensive patients treated with converting enzyme inhibitors and the other comprising patients with no clinical signs of pathology and not receiving angiotensin-converting enzyme inhibitors. Endothelial function was assessed by measuring postischemic dilation of the humeral artery (baseline echocardiography Doppler), and intensive periodontal treatment was performed 24h later. Endothelial function was re-assessed 24h and 15 days after periodontal treatment.

  20. Effects of Sildenafil on Ventricular and Vascular Function in Heart Failure With Preserved Ejection Fraction

    PubMed Central

    Borlaug, Barry A.; Lewis, Gregory D.; McNulty, Steven E.; Semigran, Marc J.; LeWinter, Martin; Chen, Horng; Lin, Grace; Deswal, Anita; Margulies, Kenneth B.; Redfield, Margaret M.

    2015-01-01

    Background Early studies showed beneficial effects of phosphodiesterase 5 inhibitors (PDE5i) on cardiovascular function in heart failure (HF) patients, but the RELAX trial observed no improvement in exercise capacity with sildenafil treatment in subjects with HF and preserved ejection fraction (HFpEF). Methods and Results A subgroup of participants in the RELAX trial (n=48) underwent comprehensive noninvasive cardiovascular assessment before and after treatment with sildenafil or placebo in a prospective ancillary study. Left ventricular (LV) contractility was assessed by peak power index (PWR/EDV) and stroke work index (SW/EDV). Systemic arterial load was assessed by arterial elastance (Ea) and right ventricular afterload by pulmonary artery systolic pressure (PASP). Endothelial function was assessed by reactive hyperemia index (RHI) following upper arm cuff occlusion. Compared to placebo (n=25), sildenafil (n=23) decreased Ea (−0.29±0.28mmHg/ml vs +0.02±0.29, p=0.008) and tended to improve RHI (+0.30±0.45 vs −0.17±0.30, p=0.054). In contrast, LV contractility was reduced by 11–16% with sildenafil compared to placebo (ΔPWR/EDV −52±70 vs +0±40 mmHg/s, p=0.006; ΔSW/EDV +0.3±5.8 vs −6.0±5.1 mmHg, p=0.04). Sildenafil had no effect on PASP. Conclusions In subjects with HFpEF, sildenafil displayed opposing effects on ventricular and vascular function. We speculate that beneficial effects of PDE5i in the systemic vasculature and endothelium were insufficient to improve clinical status, or that the deleterious effects on left ventricular function offset any salutary vascular effects, contributing to the absence of benefit observed with sildenafil in subjects with HFpEF in the RELAX trial. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302. PMID:25782985

  1. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks

    PubMed Central

    Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

    2016-01-01

    We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

  2. Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function.

    PubMed

    Suzuki, Kunihiro; Olah, Gabor; Modis, Katalin; Coletta, Ciro; Kulp, Gabriella; Gerö, Domokos; Szoleczky, Petra; Chang, Tuanjie; Zhou, Zongmin; Wu, Lingyun; Wang, Rui; Papapetropoulos, Andreas; Szabo, Csaba

    2011-08-16

    The goal of the present studies was to investigate the role of changes in hydrogen sulfide (H(2)S) homeostasis in the pathogenesis of hyperglycemic endothelial dysfunction. Exposure of bEnd3 microvascular endothelial cells to elevated extracellular glucose (in vitro "hyperglycemia") induced the mitochondrial formation of reactive oxygen species (ROS), which resulted in an increased consumption of endogenous and exogenous H(2)S. Replacement of H(2)S or overexpression of the H(2)S-producing enzyme cystathionine-γ-lyase (CSE) attenuated the hyperglycemia-induced enhancement of ROS formation, attenuated nuclear DNA injury, reduced the activation of the nuclear enzyme poly(ADP-ribose) polymerase, and improved cellular viability. In vitro hyperglycemia resulted in a switch from oxidative phosphorylation to glycolysis, an effect that was partially corrected by H(2)S supplementation. Exposure of isolated vascular rings to high glucose in vitro induced an impairment of endothelium-dependent relaxations, which was prevented by CSE overexpression or H(2)S supplementation. siRNA silencing of CSE exacerbated ROS production in hyperglycemic endothelial cells. Vascular rings from CSE(-/-) mice exhibited an accelerated impairment of endothelium-dependent relaxations in response to in vitro hyperglycemia, compared with wild-type controls. Streptozotocin-induced diabetes in rats resulted in a decrease in the circulating level of H(2)S; replacement of H(2)S protected from the development of endothelial dysfunction ex vivo. In conclusion, endogenously produced H(2)S protects against the development of hyperglycemia-induced endothelial dysfunction. We hypothesize that, in hyperglycemic endothelial cells, mitochondrial ROS production and increased H(2)S catabolism form a positive feed-forward cycle. H(2)S replacement protects against these alterations, resulting in reduced ROS formation, improved endothelial metabolic state, and maintenance of normal endothelial function.

  3. Effects of resistance training combined with vascular occlusion or hypoxia on neuromuscular function in athletes.

    PubMed

    Manimmanakorn, Apiwan; Manimmanakorn, Nuttaset; Taylor, Robert; Draper, Nick; Billaut, Francois; Shearman, Jeremy P; Hamlin, Michael J

    2013-07-01

    The aim was to investigate the effects of low-load resistant training combined with vascular occlusion or normobaric hypoxic exposure, on neuromuscular function. In a randomised controlled trial, well-trained athletes took part in a 5-week training of knee flexor/extensor muscles in which low-load resistant exercise (20% of one repetition maximum, 1-RM) was combined with either (1) an occlusion pressure of approximately 230 mmHg (KT, n = 10), (2) hypoxic air to generate an arterial blood oxygen saturation of ~80% (HT, n = 10), or (3) with no additional stimulus (CT, n = 10). Before and after training, participants completed the following tests: 3-s maximal voluntary contraction (MVC₃), 30-s MVC, and an endurance test (maximal number of repetitions at 20% 1-RM, Reps₂₀). Electromyographic activity (root mean square, RMS) was measured during tests and the cross-sectional area (CSA) of the quadriceps and hamstrings was measured pre- and post-training. Relative to CT, KT, and HT showed likely increases in MVC₃ (11.0 ± 11.9 and 15.0 ± 13.1%, mean ± 90% confidence interval), MVC₃₀ (10.2 ± 9.0 and 18.3 ± 17.4%), and Reps₂₀ (28.9 ± 23.7 and 23.3 ± 24.0%). Compared to the CT group, CSA increased in the KT (7.6 ± 5.8) and HT groups (5.3 ± 3.0). KT had a large effect on RMS during MVC₃, compared to CT (effect size 0.8) and HT (effect size 0.8). We suspect hypoxic conditions created within the muscles during vascular occlusion and hypoxic training may play a key role in these performance enhancements.

  4. Lexical and Affective Prosody in Children with High Functioning Autism

    PubMed Central

    Grossman, Ruth B.; Bemis, Rhyannon H.; Skwerer, Daniela Plesa; Tager-Flusberg, Helen

    2012-01-01

    Purpose We investigated perception and production of lexical stress and processing of affective prosody in adolescents with high functioning autism (HFA). We hypothesized preserved processing of lexical and affective prosody, but atypical lexical prosody production. Method 16 children with HFA and 15 typically developing (TD) peers participated in three experiments: 1. Perception of affective prosody, 2. Lexical stress perception, 3. Lexical stress production. In Experiment 1, participants labeled sad, happy, and neutral spoken sentences that were low-pass filtered, to eliminate verbal content. In Experiment 2 participants disambiguated word meanings based on lexical stress (HOTdog, vs. hotDOG). In Experiment 3 participants produced these words in a sentence completion task. Productions were analyzed using acoustic measures. Results Accuracy levels showed no group differences. Participants with HFA could determine affect from filtered sentences and disambiguate words based on lexical stress. They produced appropriately differentiated lexical stress patterns but demonstrated atypically long productions indicating reduced ability in natural prosody production. Conclusions Children with HFA were as capable as their TD peers in receptive tasks of lexical stress and affective prosody. Prosody productions were atypically long, despite accurate differentiation of lexical stress patterns. Future research should use larger samples and spontaneous vs. elicited productions. PMID:20530388

  5. Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

    PubMed

    Haynes, Andrew; Linden, Matthew D; Chasland, Lauren C; Nosaka, Kazunori; Maiorana, Andrew J; Dawson, Ellen Adele; Dembo, Lawrence; Naylor, Louise H; Green, Daniel J

    2017-03-16

    Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF is scant. Eccentric (ECC) cycling is a novel exercise modality which may be particularly suited to patients with CHF, but the acute impacts of ECC on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC increased baseline artery diameter (pre: 4.0±0.8mm vs post: 4.2±0.7mm, P=0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for the decrease in FMD post-ECC was no longer significant. No changes were apparent after CON. Neither ECC nor CON resulted in changes to any platelet function measures (all P>0.05). These results suggest both ECC and CON cycling at a moderate intensity and short duration can be performed by patients with HFrEF, without detrimental impacts on vascular or platelet function.

  6. Microvesicles Derived from Inflammation-Challenged Endothelial Cells Modulate Vascular Smooth Muscle Cell Functions

    PubMed Central

    Pan, Qunwen; Liu, Hua; Zheng, Chunyan; Zhao, Yuhui; Liao, Xiaorong; Wang, Yan; Chen, Yanfang; Zhao, Bin; Lazartigues, Eric; Yang, Yi; Ma, Xiaotang

    2017-01-01

    Purpose: Microvesicles (MV) can modulate the function of recipient cells by transferring their contents. Our previous study highlighted that MV released from tumor necrosis factor-α (TNF-α) plus serum deprivation (SD)-stimulated endothelial progenitor cells, induce detrimental effects on endothelial cells. In this study, we investigated the potential effects of endothelial MV (EMV) on proliferation, migration, and apoptosis of human brain vascular smooth cells (HBVSMC). Methods: EMV were prepared from human brain microvascular endothelial cells (HBMEC) cultured in a TNF-α plus SD medium. RNase-EMV were made by treating EMV with RNase A for RNA depletion. The proliferation, apoptosis and migration abilities of HBVSMC were determined after co-culture with EMV or RNase-EMV. The Mek1/2 inhibitor, PD0325901, was used for pathway analysis. Western blot was used for analyzing the proteins of Mek1/2, Erk1/2, phosphorylation Erk1/2, activated caspase-3 and Bcl-2. The level of miR-146a-5p was measured by qRT-PCR. Results: (1) EMV significantly promoted the proliferation and migration of HBVSMC. The effects were accompanied by an increase in Mek1/2 and p-Erk1/2, which could be abolished by PD0325901; (2) EMV decreased the apoptotic rate of HBVSMC by approximately 35%, which was accompanied by cleaved caspase-3 down-regulation and Bcl-2 up-regulation; (3) EMV increased miR-146a-5p level in HBVSMC by about 2-folds; (4) RNase-treated EMV were less effective than EMV on HBVSMC activities and miR-146a-5p expression. Conclusion: EMV generated under inflammation challenge can modulate HBVSMC function and fate via their carried RNA. This is associated with activation of theMek1/2/Erk1/2 pathway and caspase-3/Bcl-2 regulation, during which miR-146a-5p may play an important role. The data suggest that EMV derived from inflammation-challenged endothelial cells are detrimental to HBVSMC homeostatic functions, highlighting potential novel therapeutic targets for vascular diseases. PMID

  7. A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers.

    PubMed

    Del Bó, Cristian; Riso, Patrizia; Campolo, Jonica; Møller, Peter; Loft, Steffen; Klimis-Zacas, Dorothy; Brambilla, Ada; Rizzolo, Anna; Porrini, Marisa

    2013-03-01

    It has been suggested that anthocyanin-rich foods may exert antioxidant effects and improve vascular function as demonstrated mainly in vitro and in the animal model. Blueberries are rich sources of anthocyanins and we hypothesized that their intake could improve cell protection against oxidative stress and affect endothelial function in humans. The aim of the study was to investigate the effect of one portion (300 g) of blueberries on selected markers of oxidative stress and antioxidant protection (endogenous and oxidatively induced DNA damage) and of vascular function (changes in peripheral arterial tone and plasma nitric oxide levels) in male subjects. In a randomized cross-over design, separated by a wash out period ten young volunteers received one portion of blueberries ground by blender or one portion of a control jelly. Before and after consumption (at 1, 2, and 24 hours), blood samples were collected and used to evaluate anthocyanin absorption (through mass spectrometry), endogenous and H(2)O(2)-induced DNA damage in blood mononuclear cells (through the comet assay), and plasma nitric oxide concentrations (through a fluorometric assay). Peripheral arterial function was assessed by means of Endo-PAT 2000. Blueberries significantly reduced (P < .01) H(2)O(2)-induced DNA damage (-18%) 1 hour after blueberry consumption compared to control. No significant differences were observed for endogenous DNA damage, peripheral arterial function and nitric oxide levels after blueberry intake. In conclusion, one portion of blueberries seems sufficient to improve cell antioxidant defense against DNA damage, but further studies are necessary to understand their role on vascular function.

  8. Effects of increased physical activity on body composition, physical functions, vascular functions, HR-QOL, and self-efficacy in community-dwelling elderly people.

    PubMed

    Morisawa, Tomoyuki; Tamaki, Akira; Nagai, Kotatsu; Tsukagoshi, Rui; Nozaki, Sonoko; Miyamoto, Toshiaki; Mori, Akiko; Kaya, Mitsumasa; Fujioka, Hiroyuki

    2017-01-01

    [Purpose] The objective of this study was to clarify the effects of increased number of steps on body composition, physical functions, vascular functions, health-related quality of life (HR-QOL) and self-efficacy in elderly people. [Subjects and Methods] The subjects were 47 elderly persons who resided in Port Island in the Chuo Ward of Kobe City in Hyogo Prefecture, Japan. After the calculation of the mean preintervention physical activity (PA), the subjects were instructed to increase their PA to a target baseline + 1,300 steps/day. Body composition, physical functions, vascular functions, HR-QOL, and self-efficacy were measured at baseline, after 3 and 6 months. These items were compared between a group that increased their PA and a group that did not. [Results] After 6 months, 26.1% of the subjects achieved the PA target. No significant improvements were observed in body composition, physical functions, vascular functions, or self-efficacy for either group after 3 and 6 months. However, the HR-QOL improved significantly after 6 months in the achievement group. [Conclusion] Although the intervention to increase PA did not produce significant improvements after 6 months in body composition, physical functions, vascular functions, or self-efficacy, the HR-QOL improved significantly during this relatively short period.

  9. Effects of increased physical activity on body composition, physical functions, vascular functions, HR-QOL, and self-efficacy in community-dwelling elderly people

    PubMed Central

    Morisawa, Tomoyuki; Tamaki, Akira; Nagai, Kotatsu; Tsukagoshi, Rui; Nozaki, Sonoko; Miyamoto, Toshiaki; Mori, Akiko; Kaya, Mitsumasa; Fujioka, Hiroyuki

    2017-01-01

    [Purpose] The objective of this study was to clarify the effects of increased number of steps on body composition, physical functions, vascular functions, health-related quality of life (HR-QOL) and self-efficacy in elderly people. [Subjects and Methods] The subjects were 47 elderly persons who resided in Port Island in the Chuo Ward of Kobe City in Hyogo Prefecture, Japan. After the calculation of the mean preintervention physical activity (PA), the subjects were instructed to increase their PA to a target baseline + 1,300 steps/day. Body composition, physical functions, vascular functions, HR-QOL, and self-efficacy were measured at baseline, after 3 and 6 months. These items were compared between a group that increased their PA and a group that did not. [Results] After 6 months, 26.1% of the subjects achieved the PA target. No significant improvements were observed in body composition, physical functions, vascular functions, or self-efficacy for either group after 3 and 6 months. However, the HR-QOL improved significantly after 6 months in the achievement group. [Conclusion] Although the intervention to increase PA did not produce significant improvements after 6 months in body composition, physical functions, vascular functions, or self-efficacy, the HR-QOL improved significantly during this relatively short period. PMID:28210063

  10. Exploration of the Rapid Effects of Personal Fine Particulate Matter Exposure on Hemodynamics and Vascular Function during the Same Day

    EPA Science Inventory

    Background: Levels of fine particulate matter [≤ 2.5 μm in aerodynamic diameter (PM2.5)] are associated with alterations in arterial hemodynamics and vascular function. However, the characteristics of the same-day exposure–response relationships remain unclear. Object...

  11. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects.

    PubMed

    García, José R; Clark, Amy Y; García, Andrés J

    2016-04-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded poly(ethylene glycol) (PEG) hydrogels functionalized with either a triple-helical, α2 β1 integrin-specific peptide GGYGGGP(GPP)5 GFOGER(GPP)5 GPC (GFOGER) or an αv β3 integrin-targeting peptide GRGDSPC (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration.

  12. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects

    PubMed Central

    García, José R.; Clark, Amy Y.; García, Andrés J.

    2016-01-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded polyethylene glycol (PEG) hydrogels functionalized with either a triple-helical, α2β1 integrin-specific peptide (GFOGER) or an αvβ3 integrin-targeting peptide (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration. PMID:26662727

  13. Functional Region Annotation of Liver CT Image Based on Vascular Tree

    PubMed Central

    Chen, Yufei; Wang, Gang

    2016-01-01

    Anatomical analysis of liver region is critical in diagnosis and treatment of liver diseases. The reports of liver region annotation are helpful for doctors to precisely evaluate liver system. One of the challenging issues is to annotate the functional regions of liver through analyzing Computed Tomography (CT) images. In this paper, we propose a vessel-tree-based liver annotation method for CT images. The first step of the proposed annotation method is to extract the liver region including vessels and tumors from the CT scans. And then a 3-dimensional thinning algorithm is applied to obtain the spatial skeleton and geometric structure of liver vessels. With the vessel skeleton, the topology of portal veins is further formulated by a directed acyclic graph with geometrical attributes. Finally, based on the topological graph, a hierarchical vascular tree is constructed to divide the liver into eight segments according to Couinaud classification theory and thereby annotate the functional regions. Abundant experimental results demonstrate that the proposed method is effective for precise liver annotation and helpful to support liver disease diagnosis. PMID:27891516

  14. Localization and function of KLF4 in cytoplasm of vascular smooth muscle cell

    SciTech Connect

    Liu, Yan; Zheng, Bin; Zhang, Xin-hua; Nie, Chan-juan; Li, Yong-hui; Wen, Jin-kun

    2013-06-28

    Highlights: •PDGF-BB prompts the translocation of KLF4 to the cytoplasm. •PDGF-BB promotes interaction between KLF4 and actin in the cytoplasm. •Phosphorylation and SUMOylation of KLF4 participates in regulation of cytoskeletal organization. •KLF4 regulates cytoskeleton by promoting the expression of contraction-associated genes. -- Abstract: The Krüppel-like factor 4 is a DNA-binding transcriptional regulator that regulates a diverse array of cellular processes, including development, differentiation, proliferation, and apoptosis. The previous studies about KLF4 functions mainly focused on its role as a transcription factor, its functions in the cytoplasm are still unknown. In this study, we found that PDGF-BB could prompt the translocation of KLF4 to the cytoplasm through CRM1-mediated nuclear export pathway in vascular smooth muscle cells (VSMCs) and increased the interaction of KLF4 with actin in the cytoplasm. Further study showed that both KLF4 phosphorylation and SUMOylation induced by PDGF-BB participates in regulation of cytoskeletal organization by stabilizing the actin cytoskeleton in VSMCs. In conclusion, these results identify that KLF4 participates in the cytoskeletal organization by stabilizing cytoskeleton in the cytoplasm of VSMCs.

  15. Does the DASH diet lower blood pressure by altering peripheral vascular function?

    PubMed

    Hodson, L; Harnden, K E; Roberts, R; Dennis, A L; Frayn, K N

    2010-05-01

    We tested whether lowering of blood pressure (BP) on the dietary approaches to stop hypertension (DASH) diet was associated with changes in peripheral vascular function: endothelial function, assessed by flow-mediated vasodilatation (FMD) of the brachial artery, and subcutaneous adipose tissue blood flow (ATBF). We also assessed effects on heart rate variability (HRV) as a measure of autonomic control of the heart. We allocated 27 men and women to DASH diet and control groups. We measured FMD, ATBF and HRV on fasting and after ingestion of 75 g glucose, before and after 30 days on dietary intervention, aiming for weight maintenance. The control group did not change their diet. The DASH-diet group complied with the diet as shown by significant reductions in systolic (P<0.001) and diastolic (P=0.005) BP, and in plasma C-reactive protein (P<0.01), LDL-cholesterol (P<0.01) and apolipoprotein B (P=0.001), a novel finding. Body weight changed by <1 kg. There were no changes in the control group. We found no changes in FMD, or in ATBF, in the DASH-diet group, although heart rate fell (P<0.05). Glucose and insulin concentrations did not change. In this small-scale study, the DASH diet lowered BP independently of peripheral mechanisms.

  16. Role of folic acid in nitric oxide bioavailability and vascular endothelial function.

    PubMed

    Stanhewicz, Anna E; Kenney, W Larry

    2017-01-01

    Folic acid is a member of the B-vitamin family and is essential for amino acid metabolism. Adequate intake of folic acid is vital for metabolism, cellular homeostasis, and DNA synthesis. Since the initial discovery of folic acid in the 1940s, folate deficiency has been implicated in numerous disease states, primarily those associated with neural tube defects in utero and neurological degeneration later in life. However, in the past decade, epidemiological studies have identified an inverse relation between both folic acid intake and blood folate concentration and cardiovascular health. This association inspired a number of clinical studies that suggested that folic acid supplementation could reverse endothelial dysfunction in patients with cardiovascular disease (CVD). Recently, in vitro and in vivo studies have begun to elucidate the mechanism(s) through which folic acid improves vascular endothelial function. These studies, which are the focus of this review, suggest that folic acid and its active metabolite 5-methyl tetrahydrofolate improve nitric oxide (NO) bioavailability by increasing endothelial NO synthase coupling and NO production as well as by directly scavenging superoxide radicals. By improving NO bioavailability, folic acid may protect or improve endothelial function, thereby preventing or reversing the progression of CVD in those with overt disease or elevated CVD risk.

  17. Red wine polyphenols correct vascular function injured by chronic carbon tetrachloride intoxication.

    PubMed

    Cačányiová, Soňa; Pecháňová, Oľga; Babál, Pavel; Cerná, Andrea; Janega, Pavol; Andriantsitohaina, Ramaroson

    2011-06-01

    The aim of the study was to evaluate the effect of red wine polyphenols extract Provinols™ on the development of cardiovascular injury in the model of carbon tetrachloride (CCl4) intoxication. We followed the thoracic aorta vasoactivity and left ventricle nitric oxide (NO) synthase activity in male Wistar rats. In the preventive experiment lasting for 12 weeks the control group, the group receiving CCl4 (0.5 ml/kg) two times a week subcutaneously, the group receiving Provinols™ (30 mg/kg/day) in drinking water and the group receiving CCl4+Provinols™ was used. In the recovery experiment, the initial 12 weeks of CCl4 treatment were followed by 3 weeks of spontaneous recovery or recovery with Provinols™. CCl4-intoxication resulted in the injury of vasoactivity which was demonstrated by the inhibition of acetylcholine-induced relaxation as well as noradrenaline-induced contraction. In the preventive as well as recovery experiment administration of polyphenols refreshed endothelium-dependent relaxant response and normalized inhibited contraction to adrenergic stimuli. Provinols™ treatment significantly increased NO-synthase activity in all groups. The results revealed beneficial effects of red wine polyphenols on vascular function injured by chronic CCl4 intoxication. The correction of endothelial function seems to be attributed to the activation of NO pathway by polyphenols.

  18. Vascular functioning and the water balance of ripening kiwifruit (Actinidia chinensis) berries.

    PubMed

    Clearwater, Michael J; Luo, Zhiwei; Ong, Sam Eng Chye; Blattmann, Peter; Thorp, T Grant

    2012-03-01

    Indirect evidence suggests that water supply to fleshy fruits during the final stages of development occurs through the phloem, with the xylem providing little water, or acting as a pathway for water loss back to the plant. This inference was tested by examining the water balance and vascular functioning of ripening kiwifruit berries (Actinidia chinensis var. chinensis 'Hort16A') exhibiting a pre-harvest 'shrivel' disorder in California, and normal development in New Zealand. Dye labelling and mass balance experiments indicated that the xylem and phloem were both functional and contributed approximately equally to the fruit water supply during this stage of development. The modelled fruit water balance was dominated by transpiration, with net water loss under high vapour pressure deficit (D(a)) conditions in California, but a net gain under cooler New Zealand conditions. Direct measurement of pedicel sap flow under controlled conditions confirmed inward flows in both the phloem and xylem under conditions of both low and high D(a). Phloem flows were required for growth, with gradual recovery after a step increase in D(a). Xylem flows alone were unable to support growth, but did supply transpiration and were responsive to D(a)-induced pressure fluctuations. The results suggest that the shrivel disorder was a consequence of a high fruit transpiration rate, and that the perception of complete loss or reversal of inward xylem flows in ripening fruits should be re-examined.

  19. Functional significance of preserved affect recognition in schizophrenia

    PubMed Central

    Fiszdon, Joanna M.; Johannesen, Jason K.

    2009-01-01

    Affect recognition (AR) is a core component of social information processing, thus may be critical to understanding social behavior and functioning in broader aspects of daily living. Deficits in AR are well documented in schizophrenia, however, there is also evidence that many individuals with schizophrenia perform AR tasks at near-normal levels. In the current study, we sought to evaluate the functional significance of AR deficits in schizophrenia by comparing subgroups with normal-range and impaired AR performance on proxy and interviewer-rated measures of real-world functioning. Schizophrenia outpatients were classified as normal-range (N=17) and impaired (N=31) based on a logistic cut point in the sample distribution of BLERT scores, referenced to a normative sample of healthy control subjects (N=56). The derived schizophrenia subgroups were then compared on proxy (UCSD, UPSA, SSPA, MMAA) and interviewer-rated (QLS, ILSS) measures of functioning, as well as battery of neurocognitive tests. Initial analyses indicated superior MMAA and QLS performance in the near-normal AR subgroup. Covariate analyses indicated that group differences in neurocognition fully mediated the observed associations between AR and MMAA and attenuated the observed relationships between AR classification and QLS. These results support three main conclusions. First, AR, like many other domains of psychopathology studied in schizophrenia, is preserved in select subgroups. Second, there is a positive relationship between AR performance and functional outcome measures. Third, neurocognition appears to mediate the relationship between AR and measures of functioning. PMID:20202689

  20. Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction

    PubMed Central

    LeBlanc, Amanda J.; Touroo, Jeremy S.; Hoying, James B.

    2012-01-01

    A three-dimensional tissue construct was created using adipose-derived stromal vascular fraction (SVF) cells and evaluated as a microvascular protection treatment in a myocardial infarction (MI) model. This study evaluated coronary blood flow (BF) and global left ventricular function after MI with and without the SVF construct. Fischer-344 rats were separated into four groups: sham operation (sham), MI, MI Vicryl patch (no cells), and MI SVF construct (MI SVF). SVF cells were labeled with green fluorescent protein (GFP). Immediately postinfarct, constructs were implanted onto the epicardium at the site of ischemia. Four weeks postsurgery, the coronary BF reserve was significantly decreased by 67% in the MI group and 75% in the MI Vicryl group compared with the sham group. The coronary BF reserve of the sham and MI SVF groups in the area at risk was not significantly different (sham group: 83 ± 22% and MI SVF group: 57 ± 22%). Griffonia simplicifolia I and GFP-positive SVF immunostaining revealed engrafted SVF cells around microvessels in the infarct region 4 wk postimplant. Overall heart function, specifically ejection fraction, was significantly greater in MI SVF hearts compared with MI and MI Vicryl hearts (MI SVF: 66 ± 4%, MI: 37 ± 8%, and MI Vicryl: 29 ± 6%). In conclusion, adipose-derived SVF cells can be used to construct a novel therapeutic modality for treating microvascular instability and ischemia through implantation on the epicardial surface of the heart. The SVF construct implanted immediately after MI not only maintains heart function but also sustains microvascular perfusion and function in the infarct area by sustaining the coronary BF reserve. PMID:22140045

  1. Endothelial Mineralocorticoid Receptors Differentially Contribute to Coronary and Mesenteric Vascular Function Without Modulating Blood Pressure.

    PubMed

    Mueller, Katelee Barrett; Bender, Shawn B; Hong, Kwangseok; Yang, Yan; Aronovitz, Mark; Jaisser, Frederic; Hill, Michael A; Jaffe, Iris Z

    2015-11-01

    Arteriolar vasoreactivity tightly regulates tissue-specific blood flow and contributes to systemic blood pressure (BP) but becomes dysfunctional in the setting of cardiovascular disease. The mineralocorticoid receptor (MR) is known to regulate BP via the kidney and by vasoconstriction in smooth muscle cells. Although endothelial cells (EC) express MR, the contribution of EC-MR to BP and resistance vessel function remains unclear. To address this, we created a mouse with MR specifically deleted from EC (EC-MR knockout [EC-MR-KO]) but with intact leukocyte MR expression and normal renal MR function. Telemetric BP studies reveal no difference between male EC-MR-KO mice and MR-intact littermates in systolic, diastolic, circadian, or salt-sensitive BP or in the hypertensive responses to aldosterone±salt or angiotensin II±l-nitroarginine methyl ester. Vessel myography demonstrated normal vasorelaxation in mesenteric and coronary arterioles from EC-MR-KO mice. After exposure to angiotensin II-induced hypertension, impaired endothelial-dependent relaxation was prevented in EC-MR-KO mice in mesenteric vessels but not in coronary vessels. Mesenteric vessels from angiotensin II-exposed EC-MR-KO mice showed increased maximum responsiveness to acetylcholine when compared with MR-intact vessels, a difference that is lost with indomethacin+l-nitroarginine methyl ester pretreatment. These data support that EC-MR plays a role in regulating endothelial function in hypertension. Although there was no effect of EC-MR deletion on mesenteric vasoconstriction, coronary arterioles from EC-MR-KO mice showed decreased constriction to endothelin-1 and thromboxane agonist at baseline and also after exposure to hypertension. These data support that EC-MR participates in regulation of vasomotor function in a vascular bed-specific manner that is also modulated by risk factors, such as hypertension.

  2. Regional MRI Diffusion, White-Matter Hyperintensities, and Cognitive Function in Alzheimer's Disease and Vascular Dementia

    PubMed Central

    Scrascia, Federica; Quattrocchi, Carlo Cosimo; Errante, Yuri; Gangemi, Emma; Curcio, Giuseppe; Ursini, Francesca; Silvestrini, Mauro; Maggio, Paola; Beomonte Zobel, Bruno; Rossini, Paolo Maria; Pasqualetti, Patrizio; Falsetti, Lorenzo; Vernieri, Fabrizio

    2016-01-01

    Background and Purpose An increase in brain water diffusivity as measured using magnetic resonance imaging (MRI) has been recently reported in normal-appearing white matter (NAWM) in patients affected by cognitive impairment. However, it remains to be clarified if this reflects an overt neuronal tissue disruption that leads to degenerative or microvascular lesions. This question was addressed by comparing the regional MRI apparent diffusion coefficients (ADCs) of NAWM in patients affected by Alzheimer's disease (AD) or vascular dementia (VaD). The relationships of ADCs with the white-matter hyperintensity (WMH) burden, carotid atherosclerosis, and cognitive performance were also investigated. Methods Forty-nine AD and 31 VaD patients underwent brain MRI to assess the WMH volume and regional NAWM ADCs, neuropsychological evaluations, and carotid ultrasound to assess the plaque severity and intima-media thickness (IMT). Results Regional ADCs in NAWM did not differ between VaD and AD patients, while the WMH volume was greater in VaD than in AD patients. The ADC in the anterior corpus callosum was related to the WMH volume, while a greater carotid IMT was positively correlated with the temporal ADC and WMH volume. The memory performance was worse in patients with higher temporal ADCs. Constructional praxis scores were related to ADCs in the frontal, and occipital lobes, in the anterior and posterior corpus callosum as well as to the WMH volume. Abstract reasoning was related to frontal, parietal, and temporal ADCs. Conclusions Our data show that higher regional ADCs in NAWM are associated with microcirculatory impairment, as depicted by the WMH volume. Moreover, regional ADCs in NAWM are differently associated with the neuropsychological performances in memory, constructional praxia, and abstract reasoning domains. PMID:27074295

  3. Effects of black raspberry on lipid profiles and vascular endothelial function in patients with metabolic syndrome.

    PubMed

    Jeong, Han Saem; Hong, Soon Jun; Lee, Tae-Bum; Kwon, Ji-Wung; Jeong, Jong Tae; Joo, Hyung Joon; Park, Jae Hyoung; Ahn, Chul-Min; Yu, Cheol Woong; Lim, Do-Sun

    2014-10-01

    Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p < 0.05, respectively) and total cholesterol/HDL ratio (-0.31 ± 0.64 vs. 0.07 ± 0.58, p < 0.05, respectively) were significantly greater in the group with black raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p < 0.05, respectively). Decreases from the baseline in IL-6 (-0.4 ± 1.5 pg/mL vs. -0.1 ± 1.0 pg/mL, p < 0.05, respectively) and TNF-α (-2.9 ± 4.7 pg/mL vs. 0.1 ± 3.6 pg/mL, p < 0.05, respectively) were significantly greater in the group with black raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up.

  4. Montmorency Tart cherries (Prunus cerasus L.) modulate vascular function acutely, in the absence of improvement in cognitive performance.

    PubMed

    Keane, K M; Haskell-Ramsay, C F; Veasey, R C; Howatson, G

    2016-12-01

    Cerebral blood volume and metabolism of oxygen decline as part of human ageing, and this has been previously shown to be related to cognitive decline. There is some evidence to suggest that polyphenol-rich foods can play an important role in delaying the onset or halting the progression of age-related health disorders such as CVD and Alzheimer's disease and to improve cognitive function. In the present study, an acute, placebo-controlled, double-blinded, cross-over, randomised Latin-square design study with a washout period of at least 14 d was conducted on twenty-seven, middle-aged (defined as 45-60 years) volunteers. Participants received either a 60 ml dose of Montmorency tart cherry concentrate (MC), which contained 68·0 (sd 0·26) mg cyanidin-3-glucoside/l, 160·75 (sd 0·55) mean gallic acid equivalent/l and 0·59 (sd 0·02) mean Trolox equivalent/l, respectively, or a placebo. Cerebrovascular responses, cognitive performance and blood pressure were assessed at baseline and 1, 2, 3 and 5 h following consumption. There were significant differences in concentrations of total Hb and oxygenated Hb during the task period 1 h after MC consumption (P≤0·05). Furthermore, MC consumption significantly lowered systolic blood pressure (P≤0·05) over a period of 3 h, with peak reductions of 6±2 mmHg at 1 h after MC consumption relative to the placebo. Cognitive function and mood were not affected. These results show that a single dose of MC concentrate can modulate certain variables of vascular function; however, this does not translate to improvements in cognition or mood.

  5. Vascular function, cerebral cortical thickness, and cognitive performance in middle-aged Hispanic and non-Hispanic Caucasian adults.

    PubMed

    Pasha, Evan P; Kaur, Sonya S; Gonzales, Mitzi M; Machin, Daniel R; Kasischke, Kennon; Tanaka, Hirofumi; Haley, Andreana P

    2015-04-01

    Hispanics are at increased risk for acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health with measures of cerebral gray matter integrity, 60 middle-aged Hispanic and non-Hispanic Caucasian participants were matched across age, sex, years of education, and mental status. Arterial stiffness was characterized by β-stiffness index and carotid-femoral pulse wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non-Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (P=.04) with concurrently lower language (P=.02), memory (P=.03), and attention-executive functioning (P=.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics.

  6. Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy

    PubMed Central

    Arima, Mitsuru; Cui, Dan; Kimura, Tokuhiro; Sonoda, Koh-Hei; Ishibashi, Tatsuro; Matsuda, Satoshi; Ikeda, Eiji

    2016-01-01

    Despite the advance in medical technology, diabetic retinopathy (DR) is still an intractable disease which leads to the damage of retinal cells and finally the visual loss. Impairment of retinal vascular barrier triggered by an admixture of multiple inflammatory cytokines is a core of pathophysiology of DR. Therefore, the molecules involved commonly in multiple cytokines-induced impairment of vascular barrier would be the targets of curative treatment of DR. Here, we demonstrate that basigin, a transmembrane molecule expressed in neural barrier-forming endothelial cells, is the molecule essential for vascular barrier impairment which is shared by various triggers including VEGF, TNFα and IL-1β. In vitro data with neural microvascular endothelial cells indicated that stimulation with cytokines decreases the levels of claudin-5 in cell membranes and consequently impairs the barrier function in a manner dependent on the interaction of claudin-5 with basigin and caveolin-1. In addition, the increased vascular permeability in retinas of streptozotocin-induced diabetic mice was shown to be clearly normalized by intravitreous injection of siRNAs specific for basigin. This study has highlighted basigin as a common essential molecule for various stimuli-induced impairment of retinal vascular barrier, which can be a target for strategies to establish a curative treatment of DR. PMID:27917946

  7. New Indices of Endothelial Function Measured by Digital Thermal Monitoring of Vascular Reactivity: Data from 6084 Patients Registry.

    PubMed

    Naghavi, Morteza; Yen, Albert A; Lin, Alex W H; Tanaka, Hirofumi; Kleis, Stanley

    2016-01-01

    Background. Endothelial function is viewed as a barometer of cardiovascular health and plays a central role in vascular reactivity. Several studies showed digital thermal monitoring (DTM) as a simple noninvasive method to measure vascular reactivity that is correlated with atherosclerosis risk factors and coronary artery disease. Objectives. To further evaluate the relations between patient characteristics and DTM indices in a large patient registry. Methods. DTM measures were correlated with age, sex, heart rate, and systolic and diastolic blood pressure in 6084 patients from 18 clinics. Results. DTM vascular reactivity index (VRI) was normally distributed and inversely correlated with age (r = -0.21, p < 0.0001). Thirteen percent of VRI tests were categorized as poor vascular reactivity (VRI < 1.0), 70 percent as intermediate (1.0 ≤ VRI < 2.0), and 17 percent as good (VRI ≥ 2.0). Poor VRI (<1.0) was noted in 6% of <50 y, 10% of 50-70 y, and 18% of ≥70 y. In multiple linear regression analyses, age, sex, and diastolic blood pressure were significant but weak predictors of VRI. Conclusions. As the largest database of finger-based vascular reactivity measurement, this report adds to prior findings that VRI is a meaningful physiological marker and reflects a high level of residual risk found in patients currently under care.

  8. New Indices of Endothelial Function Measured by Digital Thermal Monitoring of Vascular Reactivity: Data from 6084 Patients Registry

    PubMed Central

    Yen, Albert A.; Lin, Alex W. H.; Tanaka, Hirofumi; Kleis, Stanley

    2016-01-01

    Background. Endothelial function is viewed as a barometer of cardiovascular health and plays a central role in vascular reactivity. Several studies showed digital thermal monitoring (DTM) as a simple noninvasive method to measure vascular reactivity that is correlated with atherosclerosis risk factors and coronary artery disease. Objectives. To further evaluate the relations between patient characteristics and DTM indices in a large patient registry. Methods. DTM measures were correlated with age, sex, heart rate, and systolic and diastolic blood pressure in 6084 patients from 18 clinics. Results. DTM vascular reactivity index (VRI) was normally distributed and inversely correlated with age (r = −0.21, p < 0.0001). Thirteen percent of VRI tests were categorized as poor vascular reactivity (VRI < 1.0), 70 percent as intermediate (1.0 ≤ VRI < 2.0), and 17 percent as good (VRI ≥ 2.0). Poor VRI (<1.0) was noted in 6% of <50 y, 10% of 50–70 y, and 18% of ≥70 y. In multiple linear regression analyses, age, sex, and diastolic blood pressure were significant but weak predictors of VRI. Conclusions. As the largest database of finger-based vascular reactivity measurement, this report adds to prior findings that VRI is a meaningful physiological marker and reflects a high level of residual risk found in patients currently under care. PMID:27830091

  9. Abnormal GABAergic function and negative affect in schizophrenia.

    PubMed

    Taylor, Stephan F; Demeter, Elise; Phan, K Luan; Tso, Ivy F; Welsh, Robert C

    2014-03-01

    Deficits in the γ-aminobutyric acid (GABA) system have been reported in postmortem studies of schizophrenia, and therapeutic interventions in schizophrenia often involve potentiation of GABA receptors (GABAR) to augment antipsychotic therapy and treat negative affect such as anxiety. To map GABAergic mechanisms associated with processing affect, we used a benzodiazepine challenge while subjects viewed salient visual stimuli. Fourteen stable, medicated schizophrenia/schizoaffective patients and 13 healthy comparison subjects underwent functional magnetic resonance imaging using the blood oxygenation level-dependent (BOLD) technique while they viewed salient emotional images. Subjects received intravenous lorazepam (LRZ; 0.01 mg/kg) or saline in a single-blinded, cross-over design (two sessions separated by 1-3 weeks). A predicted group by drug interaction was noted in the dorsal medial prefrontal cortex (dmPFC) as well as right superior frontal gyrus and left and right occipital regions, such that psychosis patients showed an increased BOLD signal to LRZ challenge, rather than the decreased signal exhibited by the comparison group. A main effect of reduced BOLD signal in bilateral occipital areas was noted across groups. Consistent with the role of the dmPFC in processing emotion, state negative affect positively correlated with the response to the LRZ challenge in the dmPFC for the patients and comparison subjects. The altered response to LRZ challenge is consistent with altered inhibition predicted by postmortem findings of altered GABAR in schizophrenia. These results also suggest that negative affect in schizophrenia/schizoaffective disorder is associated-directly or indirectly-with GABAergic function on a continuum with normal behavior.

  10. No adverse affect after harvesting of free fibula osteoseptocutaneous flaps on gait function.

    PubMed

    Maurer-Ertl, Werner; Glehr, Mathias; Friesenbichler, Joerg; Sadoghi, Patrick; Wiedner, Maria; Haas, Franz; Leithner, Andreas; Windhager, Reinhard; Zwick, Ernst B

    2012-07-01

    The aim of this study was to analyze gait function and muscular strength on donor site after harvesting of a vascularized fibula osteoseptocutaneous flap. Nine patients with a mean follow-up of 33 months (range, 7-59) and a mean resection length of the middle portion of the fibula of 18.0 cm (range, 14.0-23.0) underwent an instrumented three-dimensional gait analysis to evaluate gait function. Furthermore, CYBEX II extremity system was used for muscular strength measurements. Subjective muscle strength measurements were performed according to Kendall et al. and were classified according to the British Medical Research Council. Intraindividual comparison between the operated and the nonoperated leg revealed no significant differences for gait function parameters (cadence, velocity, and stride length, P > 1.00) and for muscular strength measurements for flexion (knee: P = 0.93, ankle: P = 0.54) and extension (knee: P = 0.97, ankle: P= 0.21), respectively. In conclusion, intraindividual comparison of the operated and nonoperated sides after harvesting of the middle portion of the fibula for gaining a free fibula osteoseptocutaneous flap has no adverse affect on gait function or muscular flexion and extension strength on donor site at a mean follow-up of 33 months.

  11. Effects of exercise training on tumor hypoxia and vascular function in the rodent preclinical orthotopic prostate cancer model.

    PubMed

    McCullough, Danielle J; Nguyen, Linda M-D; Siemann, Dietmar W; Behnke, Bradley J

    2013-12-01

    Regular physical exercise is considered to be an integral component of cancer care strategies. However, the effect of exercise training on tumor microvascular oxygenation, hypoxia, and vascular function, all of which can affect the tumor microenvironment, remains unknown. Using an orthotopic preclinical model of prostate cancer, we tested the hypotheses that, after exercise training, in the tumor, there would be an enhanced microvascular Po2, increased number of patent vessels, and reduced hypoxia. We also investigated tumor resistance artery contractile properties. Dunning R-3327 AT-1 tumor cells (10(4)) were injected into the ventral prostate of 4-5-mo-old male Copenhagen or Nude rats, which were randomly assigned to tumor-bearing exercise trained (TB-Ex trained; n = 15; treadmill exercise for 5-7 wk) or sedentary groups (TB-Sedentary; n = 12). Phosphorescence quenching was used to measure tumor microvascular Po2, and Hoechst-33342 and EF-5 were used to measure patent vessels and tumor hypoxia, respectively. Tumor resistance artery function was assessed in vitro using the isolated microvessel technique. Compared with sedentary counterparts, tumor microvascular Po2 increased ∼100% after exercise training (TB-Sedentary, 6.0 ± 0.3 vs. TB-Ex Trained, 12.2 ± 1.0 mmHg, P < 0.05). Exercise training did not affect the number of patent vessels but did significantly reduce tumor hypoxia in the conscious, resting condition from 39 ± 12% of the tumor area in TB-Sedentary to 4 ± 1% in TB-Ex Trained. Exercise training did not affect vessel contractile function. These results demonstrate that after exercise training, there is a large increase in the driving force of O2 from the tumor microcirculation, which likely contributes to the considerable reduction in tumor hypoxia. These results suggest that exercise training can modulate the microenvironment of the tumor, such that a sustained reduction in tumor hypoxia occurs, which may lead to a less aggressive phenotype and

  12. DNA Damage and Repair in Vascular Disease.

    PubMed

    Uryga, Anna; Gray, Kelly; Bennett, Martin

    2016-01-01

    DNA damage affecting both genomic and mitochondrial DNA is present in a variety of both inherited and acquired vascular diseases. Multiple cell types show persistent DNA damage and a range of lesions. In turn, DNA damage activates a variety of DNA repair mechanisms, many of which are activated in vascular disease. Such DNA repair mechanisms either stall the cell cycle to allow repair to occur or trigger apoptosis or cell senescence to prevent propagation of damaged DNA. Recent evidence has indicated that DNA damage occurs early, is progressive, and is sufficient to impair function of cells composing the vascular wall. The consequences of persistent genomic and mitochondrial DNA damage, including inflammation, cell senescence, and apoptosis, are present in vascular disease. DNA damage can thus directly cause vascular disease, opening up new possibilities for both prevention and treatment. We review the evidence for and the causes, types, and consequences of DNA damage in vascular disease.

  13. Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques

    PubMed Central

    Silvola, Johanna M. U.; Virtanen, Helena; Siitonen, Riikka; Hellberg, Sanna; Liljenbäck, Heidi; Metsälä, Olli; Ståhle, Mia; Saanijoki, Tiina; Käkelä, Meeri; Hakovirta, Harri; Ylä-Herttuala, Seppo; Saukko, Pekka; Jauhiainen, Matti; Veres, Tibor Z.; Jalkanen, Sirpa; Knuuti, Juhani; Saraste, Antti; Roivainen, Anne

    2016-01-01

    Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples from patients with recent ischemic symptoms. In low-density lipoprotein receptor-deficient mice expressing only apolipoprotein B100 (LDLR−/−ApoB100/100), VAP-1 was expressed on endothelial cells lining inflamed atherosclerotic lesions; normal vessel walls in aortas of C57BL/6N control mice were VAP-1-negative. Second, we discovered that the focal uptake of VAP-1 targeting sialic acid-binding immunoglobulin-like lectin 9 based PET tracer [68Ga]DOTA-Siglec-9 in atherosclerotic plaques was associated with the density of activated macrophages (r = 0.58, P = 0.022). As a final point, we found that the inhibition of VAP-1 activity with small molecule LJP1586 decreased the density of macrophages in inflamed atherosclerotic plaques in mice. Our results suggest for the first time VAP-1 as a potential imaging target for inflamed atherosclerotic plaques, and corroborate VAP-1 inhibition as a therapeutic approach in the treatment of atherosclerosis. PMID:27731409

  14. Acute effect of brisk walking with graduated compression stockings on vascular endothelial function and oxidative stress.

    PubMed

    Okamoto, Takanobu; Sakamaki-Sunaga, Mikako; Min, Seokki; Miura, Takashi; Iwasaki, Tetsuji

    2013-11-01

    The purpose of this study was to investigate the acute effect of brisk walking with and without graduated compression stockings (GCSs) on vascular endothelial function and oxidative stress. Ten young healthy subjects walked briskly for 30 min with (GCS trial) and without (CON trial) GCSs in a randomized crossover trial. Brachial artery flow-mediated dilation (FMD) was measured as the per cent rise in the peak diameter from the baseline value at prior occlusion at each FMD measurement using B-mode ultrasonography before and 30 min after walking in the two trials. Derivatives of reactive oxygen metabolites (d-ROM), as an index of products of reactive oxygen species, and biological anti-oxidant potential (BAP), as an index of anti-oxidant potential, were also measured using a free radical elective evaluator before and 30 min after walking in both trials. FMD significantly decreased after brisk walking in both trials (P<0·05). However, FMD after brisk walking in the GCS trial was significantly higher than that in the CON trial (P<0·05). The d-ROM did not change before and after both trials, whereas the BAP significantly increased after walking in the GCS trial (P<0·05). These findings demonstrate that brisk walking while wearing GCSs suppresses the decrease in FMD and increases BAP.

  15. Properdistatin inhibits angiogenesis and improves vascular function in human melanoma xenografts with low thrombospondin-1 expression

    PubMed Central

    Gaustad, Jon-Vidar; Simonsen, Trude G.; Andersen, Lise Mari K.; Rofstad, Einar K.

    2016-01-01

    In this study, the effect of properdistatin, a novel peptide derived from the thrombospondin 1 (TSP-1) domain of properdin, was investigated in three melanoma xenograft models with different TSP-1 expression. The tumors were grown in dorsal window chambers and were treated with 80 mg/kg/day properdistatin or vehicle. Morphological parameters of the tumor vasculature were assessed from high resolution transillumination images. Blood supply time (i.e., the time required for arterial blood to flow from a supplying artery to downstream microvessels) and plasma velocities were assessed from first-pass imaging movies recorded after a bolus of fluorescence-labeled dextran had been administered intravenously. Gene and protein expression of TSP-1 were assessed with quantitative PCR and immunohistochemistry, respectively. Properdistatin treatment inhibited angiogenesis in low TSP-1 expressing tumors but did not alter the vasculature in high TSP-1 expressing tumors. In low TSP-1 expressing tumors, properdistatin selectively removed small-diameter capillaries, but did not change the morphology of tumor arterioles or tumor venules. Properdistatin also reduced blood supply times and increased plasma velocities, implying that the treatment reduced the geometric resistance to blood flow and improved vascular function. PMID:27756886

  16. Upregulation of functionally active vascular endothelial growth factor by human cytomegalovirus.

    PubMed

    Reinhardt, Barbara; Schaarschmidt, Peter; Bossert, Andrea; Lüske, Anke; Finkenzeller, Günter; Mertens, Thomas; Michel, Detlef

    2005-01-01

    Human cytomegalovirus (HCMV) infection is known to modulate host gene expression and has been linked to the pathogenesis of vasculopathies; however, relevant pathomechanisms are still unclear. It was shown that HCMV infection leads to upregulation of vascular endothelial growth factor (VEGF) expression in human foreskin fibroblasts and coronary artery smooth muscle cells (SMC). Activation of VEGF transcription by HCMV infection was confirmed by transient-expression experiments, which revealed that a short promoter fragment, pLuc135 (-85 to +50), is sufficient for activation. Site-directed mutagenesis of Sp1-recognition sites within this fragment abolished the upregulation of transcription. Functional VEGF protein is released into the culture supernatant of infected SMC. Incubation of endothelial cells with supernatants from HCMV-infected SMC cultures induced upregulation of VEGF receptor-2 expression on endothelial cells, as well as a significant upregulation of DNA synthesis, implicating cell proliferation. The mean incline of DNA synthesis at 48 and 72 h post-infection was 148 and 197 %, respectively. Addition of neutralizing antibodies against VEGF completely abolished this effect. Supernatants from SMC cultures incubated with UV-inactivated virus induced a comparable effect. This virus-induced paracrine effect may represent a molecular mechanism for HCMV-induced pathogenesis, such as inflammatory vasculopathies, by inducing a proatherogenic phenotype in SMC.

  17. Functional and molecular mapping of uncoupling between vascular permeability and loss of vascular maturation in ovarian carcinoma xenografts: the role of stroma cells in tumor angiogenesis.

    PubMed

    Gilad, Assaf A; Israely, Tomer; Dafni, Hagit; Meir, Gila; Cohen, Batya; Neeman, Michal

    2005-11-01

    Maintaining homogeneous perfusion in tissues undergoing remodeling and vascular expansion requires tight orchestration of the signals leading to endothelial sprouting and subsequent recruitment of perivascular contractile cells and vascular maturation. This regulation, however, is frequently disrupted in tumors. We previously demonstrated the role of tumor-associated myofibroblasts in vascularization and exit from dormancy of human ovarian carcinoma xenografts in nude mice. The aim of this work was to determine the contribution of stroma- and tumor cell-derived angiogenic growth factors to the heterogeneity of vascular permeability and maturation in MLS human ovarian carcinoma tumors. We show by RT-PCR and by in situ hybridization that VEGF was expressed by the tumor cells, while angiopoietin-1 and -2 were expressed only by the infiltrating host stroma cells. Vascular maturation was detected in vivo by vasoreactivity to hypercapnia, measured by BOLD contrast MRI and validated by immunostaining of histologic sections to alpha-smooth muscle actin. Vascular permeability was measured in vivo by dynamic contrast-enhanced MRI using albumin-based contrast material and validated in histologic sections by fluorescent staining of the biotinylated contrast material. MRI as well as histologic correlation maps between vascular maturation and vascular permeability revealed a wide range of vascular phenotypes, in which the distribution of vascular maturation and vasoreactivity did not overlap spatially with reduced permeability. The large heterogeneity in the degree of vascular maturation and permeability is consistent with the differential expression pattern of VEGF and angiopoietins during tumor angiogenesis.

  18. Functional Divergence in CO2 Exchange Among Vascular Plant Communities in a Temperate Ombrotrophic Peatland

    NASA Astrophysics Data System (ADS)

    Lai, Derrick Y. F.; Roulet, Nigel T.; Moore, Tim R.; Humphreys, Elyn R.

    2013-04-01

    Plant functional types (PFTs) are used to classify vegetation into groups that demonstrate similar responses to changes in environmental conditions. In this study, we investigated the potential for differentiating CO2 exchange among three vascular plant communities (Chamaedaphne, Maianthemum/Ledum, and Eriophorum) with different dominant species and microclimatic characteristics at the Mer Bleue bog in Canada. Using an automatic chamber system, we examined the seasonal patterns of net ecosystem CO2 exchange (NEE), gross ecosystem production (GEP), and ecosystem respiration (ER), as well as the responses of GEP and ER to changing environmental and biotic conditions among communities in 2009. While seasonal mean NEE were similar among the three plant communities, seasonal mean GEP and ER were significantly lower in the Maianthemum/Ledum community owing to the lower green biomass and higher water table. Based on the parameterized GEP models, we detected a significant decrease in effective quantum yield in the order of Eriophorum > Chamaedaphne > Maianthemum/Ledum community, indicating the most efficient photosynthetic activity in sedges at lower light levels. The rate of linear increase in GEP with vascular green area index was considerably lower in the Maianthemum/Ledum community, in relation to the high specific leaf area of forb foliage. We found that maximum gross photosynthesis (Pmax) per unit ground area had a clear seasonal pattern with a single peak in mid-summer, but Pmax per unit green area varied much less over time. This suggests that the temporal changes in community-level Pmax are predominantly controlled by variations in green area rather than variations in photosynthetic capacity per unit green area. The ER model parameters were significantly different among communities, with the highest temperature sensitivity of ER in the Eriophorum community. The three communities each represent a distinct PFT as their CO2 exchange processes respond to environmental

  19. Can the hydrophilicity of functional monomers affect chemical interaction?

    PubMed

    Feitosa, V P; Ogliari, F A; Van Meerbeek, B; Watson, T F; Yoshihara, K; Ogliari, A O; Sinhoreti, M A; Correr, A B; Cama, G; Sauro, S

    2014-02-01

    The number of carbon atoms and/or ester/polyether groups in spacer chains may influence the interaction of functional monomers with calcium and dentin. The present study assessed the chemical interaction and bond strength of 5 standard-synthesized phosphoric-acid ester functional monomers with different spacer chain characteristics, by atomic absorption spectroscopy (AAS), ATR-FTIR, thin-film x-ray diffraction (TF-XRD), scanning electron microscopy (SEM), and microtensile bond strength (μTBS). The tested functional monomers were 2-MEP (two-carbon spacer chain), 10-MDP (10-carbon), 12-MDDP (12-carbon), MTEP (more hydrophilic polyether spacer chain), and CAP-P (intermediate hydrophilicity ester spacer). The intensity of monomer-calcium salt formation measured by AAS differed in the order of 12-MDDP=10-MDP>CAP-P>MTEP>2-MEP. FTIR and SEM analyses of monomer-treated dentin surfaces showed resistance to rinsing for all monomer-dentin bonds, except with 2-MEP. TF-XRD confirmed the weaker interaction of 2-MEP. Highest µTBS was observed for 12-MDDP and 10-MDP. A shorter spacer chain (2-MEP) of phosphate functional monomers induced formation of unstable monomer-calcium salts, and lower chemical interaction and dentin bond strength. The presence of ester or ether groups within longer spacer carbon chains (CAP-P and MTEP) may affect the hydrophilicity, μTBS, and also the formation of monomer-calcium salts.

  20. How does temperature affect the function of tissue macrophages?

    NASA Astrophysics Data System (ADS)

    Lee, Chen-Ting; Repasky, Elizabeth A.

    2011-03-01

    Macrophages create a major danger signal following injury or infection and upon activation release pro-inflammatory cytokines, which in turn help to generate febrile conditions. Thus, like other cells of the body, tissue macrophages are often exposed to naturally occurring elevations in tissue temperature during inflammation and fever. However, whether macrophages sense and respond to temperature changes in a specific manner which modulates their function is still not clear. In this brief review, we highlight recent studies which have analyzed the effects of temperatures on macrophage function, and summarize the possible underlying molecular mechanisms which have been identified. Mild, physiological range hyperthermia has been shown to have both pro- and anti-inflammatory roles in regulating macrophage inflammatory cytokine production and at the meeting presentation, we will show new data demonstrating that hyperthermia can indeed exert both positive and negative signals to macrophages. While some thermal effects are correlated with the induction of heat shock factors/heat shock proteins, overall it is not clear how mild hyperthermia can exert both pro- and anti-inflammatory functions. We also summarize data which shows that hyperthermia can affect other macrophage effector functions, including the anti-tumor cytotoxicity. Overall, these studies may help us to better understand the immunological role of tissue temperature and may provide important information needed to maximize the application of heat in the treatment of various diseases including cancer.

  1. Genetic causation of neointimal hyperplasia in hemodialysis vascular access dysfunction.

    PubMed

    Lee, Timmy; Wadehra, Davinder

    2012-01-01

    The major cause of hemodialysis vascular access failure is venous stenosis resulting from neointimal hyperplasia. Genetic factors have been shown to be associated with cardiovascular disease and peripheral vascular disease (PVD) in the general population. Genetic factors may also play an important role in vascular access stenosis and development of neointimal hyperplasia by affecting pathways that lead to inflammation, endothelial function, oxidative stress, and vascular smooth muscle proliferation. This review will discuss the role of genetics in understanding neointimal hyperplasia development in hemodialysis vascular access dysfunction and other disease processes with similar neointimal hyperplasia development such as coronary artery disease and PVD.

  2. Subfailure Overstretch Injury Leads to Reversible Functional Impairment and Purinergic P2X7 Receptor Activation in Intact Vascular Tissue

    PubMed Central

    Luo, Weifeng; Guth, Christy M.; Jolayemi, Olukemi; Duvall, Craig L.; Brophy, Colleen Marie; Cheung-Flynn, Joyce

    2016-01-01

    Vascular stretch injury is associated with blunt trauma, vascular surgical procedures, and harvest of human saphenous vein for use in vascular bypass grafting. A model of subfailure overstretch in rat abdominal aorta was developed to characterize surgical vascular stretch injury. Longitudinal stretch of rat aorta was characterized ex vivo. Stretch to the haptic endpoint, where the tissues would no longer lengthen, occurred at twice the resting length. The stress produced at this length was greater than physiologic mechanical forces but well below the level of mechanical disruption. Functional responses were determined in a muscle bath, and this subfailure overstretch injury led to impaired smooth muscle function that was partially reversed by treatment with purinergic receptor (P2X7R) antagonists. These data suggest that vasomotor dysfunction caused by subfailure overstretch injury may be due to the activation of P2X7R. These studies have implications for our understanding of mechanical stretch injury of blood vessels and offer novel therapeutic opportunities. PMID:27747211

  3. NADPH Oxidases in Vascular Pathology

    PubMed Central

    Konior, Anna; Schramm, Agata; Czesnikiewicz-Guzik, Marta

    2014-01-01

    Abstract Significance: Reactive oxygen species (ROS) play a critical role in vascular disease. While there are many possible sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play a central role. They are a source of “kindling radicals,” which affect other enzymes, such as nitric oxide synthase endothelial nitric oxide synthase or xanthine oxidase. This is important, as risk factors for atherosclerosis (hypertension, diabetes, hypercholesterolemia, and smoking) regulate the expression and activity of NADPH oxidases in the vessel wall. Recent Advances: There are seven isoforms in mammals: Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2. Nox1, Nox2, Nox4, and Nox5 are expressed in endothelium, vascular smooth muscle cells, fibroblasts, or perivascular adipocytes. Other homologues have not been found or are expressed at very low levels; their roles have not been established. Nox1/Nox2 promote the development of endothelial dysfunction, hypertension, and inflammation. Nox4 may have a role in protecting the vasculature during stress; however, when its activity is increased, it may be detrimental. Calcium-dependent Nox5 has been implicated in oxidative damage in human atherosclerosis. Critical Issues: NADPH oxidase-derived ROS play a role in vascular pathology as well as in the maintenance of normal physiological vascular function. We also discuss recently elucidated mechanisms such as the role of NADPH oxidases in vascular protection, vascular inflammation, pulmonary hypertension, tumor angiogenesis, and central nervous system regulation of vascular function and hypertension. Future Directions: Understanding the role of individual oxidases and interactions between homologues in vascular disease is critical for efficient pharmacological regulation of vascular NADPH oxidases in both the laboratory and clinical practice. Antioxid. Redox Signal. 20, 2794–2814. PMID:24180474

  4. Tropomyosin variants describe distinct functional subcellular domains in differentiated vascular smooth muscle cells.

    PubMed

    Gallant, Cynthia; Appel, Sarah; Graceffa, Philip; Leavis, Paul; Lin, Jim Jung-Ching; Gunning, Peter W; Schevzov, Galina; Chaponnier, Christine; DeGnore, Jon; Lehman, William; Morgan, Kathleen G

    2011-06-01

    Tropomyosin (Tm) is known to be an important gatekeeper of actin function. Tm isoforms are encoded by four genes, and each gene produces several variants by alternative splicing, which have been proposed to play roles in motility, proliferation, and apoptosis. Smooth muscle studies have focused on gizzard smooth muscle, where a heterodimer of Tm from the α-gene (Tmsm-α) and from the β-gene (Tmsm-β) is associated with contractile filaments. In this study we examined Tm in differentiated mammalian vascular smooth muscle (dVSM). Liquid chromatography-tandem mass spectrometry (LC MS/MS) analysis and Western blot screening with variant-specific antibodies revealed that at least five different Tm proteins are expressed in this tissue: Tm6 (Tmsm-α) and Tm2 from the α-gene, Tm1 (Tmsm-β) from the β-gene, Tm5NM1 from the γ-gene, and Tm4 from the δ-gene. Tm6 is by far most abundant in dVSM followed by Tm1, Tm2, Tm5NM1, and Tm4. Coimmunoprecipitation and coimmunofluorescence studies demonstrate that Tm1 and Tm6 coassociate with different actin isoforms and display different intracellular localizations. Using an antibody specific for cytoplasmic γ-actin, we report here the presence of a γ-actin cortical cytoskeleton in dVSM cells. Tm1 colocalizes with cortical cytoplasmic γ-actin and coprecipitates with γ-actin. Tm6, on the other hand, is located on contractile bundles. These data indicate that Tm1 and Tm6 do not form a classical heterodimer in dVSM but rather describe different functional cellular compartments.

  5. Monocyte/macrophage cytokine activity regulates vascular smooth muscle cell function within a degradable polyurethane scaffold.

    PubMed

    Battiston, K G; Ouyang, B; Labow, R S; Simmons, C A; Santerre, J P

    2014-03-01

    Tissue engineering strategies rely on the ability to promote cell proliferation and migration into porous biomaterial constructs, as well as to support specific phenotypic states of the cells in vitro. The present study investigated the use of released factors from monocytes and their derived macrophages (MDM) and the mechanism by which they regulate vascular smooth muscle cell (VSMC) response in a VSMC-monocyte co-culture system within a porous degradable polyurethane (D-PHI) scaffold. VSMCs cultured in monocyte/MDM-conditioned medium (MCM), generated from the culture of monocytes/MDM on D-PHI scaffolds for up to 28 days, similarly affected VSMC contractile marker expression, growth and three-dimensional migration when compared to direct VSMC-monocyte co-culture. Monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) were identified as two cytokines present in MCM, at concentrations that have previously been shown to influence VSMC phenotype. VSMCs cultured alone on D-PHI scaffolds and exposed to MCP-1 (5 ng ml(-1)) or IL-6 (1 ng ml(-1)) for 7 days experienced a suppression in contractile marker expression (with MCP-1 or IL-6) and increased growth (with MCP-1) compared to no cytokine medium supplementation. These effects were also observed in VSMC-monocyte co-culture on D-PHI. Neutralization of IL-6, but not MCP-1, was subsequently shown to decrease VSMC growth and enhance calponin expression for VSMC-monocyte co-cultures on D-PHI scaffolds for 7 days, implying that IL-6 mediates VSMC response in monocyte-VSMC co-cultures. This study highlights the use of monocytes and their derived macrophages in conjunction with immunomodulatory biomaterials, such as D-PHI, as agents for regulating VSMC response, and demonstrates the importance of monocyte/MDM-released factors, such as IL-6 in particular, in this process.

  6. Functional groups affect physical and biological properties of dextran-based hydrogels.

    PubMed

    Sun, Guoming; Shen, Yu-I; Ho, Chia Chi; Kusuma, Sravanti; Gerecht, Sharon

    2010-06-01

    Modification of dextran backbone allows the development of a hydrogel with specific characteristics. To enhance their functionality for tissue-engineered scaffolds, a series of dextran-based macromers was synthesized by incorporating various functional groups, including allyl isocyanate (Dex-AI), ethylamine (Dex-AE), chloroacetic acid (Dex-AC), or maleic-anhydride (Dex-AM) into dextrans. The dextran-based biodegradable hybrid hydrogels are developed by integrating polyethylene glycol diacrylate (PEGDA). To explore the effect of different derivatives on hydrogel properties, three different ratios of Dex/PEGDA are examined: low (20/80), medium (40/60), and high (60/40). Differences in physical and biological properties of the hydrogels are found, including swelling, degradation rate, mechanics, crosslinking density, biocompatibility (in vitro and in vivo), and vascular endothelial growth factor release. The results also indicate that the incorporation of amine groups into dextran gives rise to hydrogels with better biocompatible and release properties. We, therefore, conclude that the incorporation of different functional groups affects the fundamental properties of a dextran-based hydrogel network, and that amine groups are preferred to generate hydrogels for biomedical use.

  7. MicroRNAs affect dendritic cell function and phenotype

    PubMed Central

    Smyth, Lesley A; Boardman, Dominic A; Tung, Sim L; Lechler, Robert; Lombardi, Giovanna

    2015-01-01

    MicroRNA (miRNA) are small, non-coding RNA molecules that have been linked with immunity through regulating/modulating gene expression. A role for these molecules in T-cell and B-cell development and function has been well established. An increasing body of literature now highlights the importance of specific miRNA in dendritic cell (DC) development as well as their maturation process, antigen presentation capacity and cytokine release. Given the unique role of DC within the immune system, linking the innate and adaptive immune responses, understanding how specific miRNA affect DC function is of importance for understanding disease. In this review we summarize recent developments in miRNA and DC research, highlighting the requirement of miRNA in DC lineage commitment from bone marrow progenitors and for the development of subsets such as plasmacytoid DC and conventional DC. In addition, we discuss how infections and tumours modulate miRNA expression and consequently DC function. PMID:25244106

  8. Bisphenol A affects androgen receptor function via multiple mechanisms.

    PubMed

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR.

  9. Vascular Cures

    MedlinePlus

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  10. CADASIL mutations and shRNA silencing of NOTCH3 affect actin organization in cultured vascular smooth muscle cells.

    PubMed

    Tikka, Saara; Ng, Yan Peng; Di Maio, Giuseppe; Mykkänen, Kati; Siitonen, Maija; Lepikhova, Tatiana; Pöyhönen, Minna; Viitanen, Matti; Virtanen, Ismo; Kalimo, Hannu; Baumann, Marc

    2012-12-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary vascular dementia caused by mutations in NOTCH3 gene. Pathology is manifested in small- and middle-sized arteries throughout the body, though primarily in cerebral white matter. Hemodynamics is altered in CADASIL and NOTCH3 is suggested to regulate actin filament polymerization and thereby vascular tone. We analyzed NOTCH3 expression and morphology of actin cytoskeleton in genetically genuine cultured human CADASIL vascular smooth muscle cells (VSMCs) (including a cell line homozygous for p.Arg133Cys mutation) derived from different organs, and in control VSMCs with short hairpin RNA (shRNA)-silenced NOTCH3. NOTCH3 protein level was higher in VSMCs derived from adult than newborn arteries in both CADASIL and control VSMCs. CADASIL VSMCs showed altered actin cytoskeleton including increased branching and node formation, and more numerous and smaller adhesion sites than control VSMCs. Alterations in actin cytoskeleton in shRNA-silenced VSMCs were similar as in CADASIL VSMCs. Severity of the alterations in actin filaments corresponded to NOTCH3 expression level being most severe in VSMCs derived from adult cerebral arteries. These observations suggest that hypomorphic NOTCH3 activity causes alterations in actin organization in CADASIL. Furthermore, arteries from different organs have specific characteristics, which modify the effects of the NOTCH3 mutation and which is one explanation for the exceptional susceptibility of cerebral white matter arteries.

  11. Relationship between circulating progenitor cells, vascular function and oxidative stress with long-term training and short-term detraining in older men.

    PubMed

    Witkowski, Sarah; Lockard, Michael M; Jenkins, Nathan T; Obisesan, Thomas O; Spangenburg, Espen E; Hagberg, James M

    2010-02-01

    Exercise may contribute to the maintenance of vascular function via enhanced liberation and action of bone-marrow-derived progenitor cells. Activity related changes in oxidative stress may also influence the number and function of these cells. In the present study, we sought to determine (i) whether adaptations in reactive hyperaemic FBF (forearm blood flow) response associated with long-term endurance exercise and short-term detraining were related to resting putative progenitor cell number and function, and (ii) whether oxidative stress affected these factors. Participants included men with a history of more than 30 years of moderate-to-high intensity exercise (HI group) and healthy low-active age- and BMI (body mass index)-matched control subjects (LO group). Vascular reactive hyperaemic FBF response, resting CD34+ and CD34+/VEGFR2+ (vascular endothelial growth factor receptor 2+] cell number, CFU-EC (colony forming unit-endothelial cell) count and CFU-EC senescence were evaluated. Oxidative stress measures included OxLDL (oxidized low-density lipoprotein) and TAC (total antioxidant capacity).These measures were assessed following 10 days of detraining in the HI group. The HI group had greater peak reactive hyperaemic FBF responses compared with the LO group, despite no difference in resting CD34+ cell number, CD34+/VEGFR2+ cell number, CFU-EC colonies or CFU-EC senescence. With detraining in the HI group, CD34+ cells declined 44 %, and the percentage change in CD34+/VEGFR2+ cells was positively correlated with the change in FBF response to reactive hyperaemia. The percentage change in CD34+/VEGFR2+ cells and the percentage change in EPC (endothelial progenitor cell) senescence with detraining were related to the percentage change in TAC. These results reveal that changes in reactive hyperaemic FBF are closely related to activity dependent dynamic changes in CD34+/VEGFR2+ cell number, which may be influenced by alterations in oxidative stress.

  12. Relationship between circulating progenitor cells, vascular function and oxidative stress with long-term training and short-term detraining in older men

    PubMed Central

    WITKOWSKI, Sarah; LOCKARD, Michael M.; JENKINS, Nathan T.; OBISESAN, Thomas O.; SPANGENBURG, Espen E.; HAGBERG, James M.

    2011-01-01

    Exercise may contribute to the maintenance of vascular function via enhanced liberation and action of bone-marrow-derived progenitor cells. Activity related changes in oxidative stress may also influence the number and function of these cells. In the present study, we sought to determine (i) whether adaptations in reactive hyperaemic FBF (forearm blood flow) response associated with long-term endurance exercise and short-term detraining were related to resting putative progenitor cell number and function, and (ii) whether oxidative stress affected these factors. Participants included men with a history of more than 30 years of moderate-to-high-intensity exercise (HI group) and healthy low-active age- and BMI (body mass index)-matched control subjects (LO group). Vascular reactive hyperaemic FBF response, resting CD34+ and CD34+/VEGFR2+ (vascular endothelial growth factor receptor 2+] cell number, CFU-EC (colony-forming unit-endothelial cell) count and CFU-EC senescence were evaluated. Oxidative stress measures included OxLDL (oxidized low-density lipoprotein) and TAC (total antioxidant capacity). These measures were assessed following 10 days of detraining in the HI group. The HI group had greater peak reactive hyperaemic FBF responses compared with the LO group, despite no difference in resting CD34+ cell number, CD34+/VEGFR2+ cell number, CFU-EC colonies or CFU-EC senescence. With detraining in the HI group, CD34+ cells declined 44 %, and the percentage change in CD34+/VEGFR2+ cells was positively correlated with the change in FBF response to reactive hyperaemia. The percentage change in CD34+/VEGFR2+ cells and the percentage change in EPC (endothelial progenitor cell) senescence with detraining were related to the percentage change in TAC. These results reveal that changes in reactive hyperaemic FBF are closely related to activity dependent dynamic changes in CD34+/VEGFR2+ cell number, which may be influenced by alterations in oxidative stress. PMID:19723023

  13. DELETION OF PROTEIN TYROSINE PHOSPHATASE 1B IMPROVES PERIPHERAL INSULIN RESISTANCE AND VASCULAR FUNCTION IN OBESE, LEPTIN RESISTANT MICE VIA REDUCED OXIDANT TONE

    PubMed Central

    Ali, M. Irfan; Ketsawatsomkron, Pimonrat; Belin de Chantelemele, Eric J.; Mintz, James D.; Muta, Kenjiro; Salet, Christina; Black, Stephen M.; Tremblay, Michel L.; Fulton, David J.; Marrero, Mario B.; Stepp, David W.

    2009-01-01

    Rationale Obesity is a risk factor for cardiovascular dysfunction, yet the underlying factors driving this impaired function remain poorly understood. Insulin resistance is a common pathology in obese patients and has been shown to impair vascular function. Whether insulin resistance or obesity, itself, is causal remains unclear. Objective The current study tested the hypothesis that insulin resistance is the underlying mediator for impaired nitric oxide mediated dilation in obesity by genetic deletion of the insulin-desensitizing enzyme protein tyrosine phosphatase 1B (PTP1B) in db/db mice. Methods and Results The db/db mouse is morbidly obese, insulin resistant and has tissue-specific elevation in PTP1B expression compared to lean controls. In db/db mice, PTP1B deletion improved glucose clearance, dyslipidemia, and insulin receptor signaling in muscle and fat. Hepatic insulin signaling in db/db mice was not improved by deletion of PTP1B, indicating specific amelioration of peripheral insulin resistance. Additionally, obese mice demonstrate an impaired endothelium dependent and independent vasodilation to acetylcholine and sodium nitroprusside, respectively. This impairment, which correlated with increased superoxide in the db/db mice, was corrected by superoxide scavenging. Increased superoxide production was associated with increased expression of NAD(P)H Oxidase 1 and its molecular regulators, Noxo1 and Noxa1. Conclusion Deletion of PTP1B improved both endothelium dependent and independent nitric oxide mediated dilation and reduced superoxide generation in db/db mice. PTP1B deletion did not affect any vascular function in lean mice. Taken together, these data reveal a role for peripheral insulin resistance as the mediator of vascular dysfunction in obesity. PMID:19797171

  14. Effect of long-term Vitamin C intake on vascular endothelial function in diabetic children and adolescents: A pilot study

    PubMed Central

    Sabri, Mohammadreza; Ghaffari, Ghafour; Hashemipour, Mahin; Mostofizadeh, Neda; Koushki, Ali Mehrabi

    2016-01-01

    Background: This study attempted to determine the effects of long-term use of Vitamin C on vascular endothelial function. Materials and Methods: During a pilot clinical trial study conducted at Imam Hussein Hospital (Isfahan) in 2014–2015, a total of forty diabetic patients were selected and then assigned randomly into two twenty-subject groups receiving Vitamin C and placebo tablets. The patients were treated with Vitamin C or placebo for 6 months. All patients were examined through echocardiography in terms of cardiac function before and after treatment. To evaluate the endothelial function (flow-mediated dilatation [FMD], intima-media thickness), they underwent arterial Doppler. Moreover, the chemical indices of vascular function were tested through intercellular adhesion molecule and vascular cell adhesion molecule (VCAM). Finally, the results were compared between the two groups. Results: Based on the results, the mean left ventricular mass significantly reduced after the intervention in the group treated with Vitamin C (from 76.35 ± 25.6–68.62 ± 22.66; P = 0.015) while there was no significant difference observed in the control group (from 67.58 ± 25.38–71.63 ± 26.84; P = 0.19) but no statistically difference between the two groups-based repeated measures ANOVA test (P = 0.6). In addition, the mean of VCAM changes was significantly difference between the two groups (P < 0.001). Conclusion: Long-term use of Vitamin C in diabetic patients can improve certain echocardiographic parameters such as ejection fraction, fractional shortening, and FMD, which in turn enhances vascular endothelial function. PMID:28255327

  15. Can lifestyle modification affect men’s erectile function?

    PubMed Central

    Hehemann, Marah C.

    2016-01-01

    Erectile dysfunction (ED) is a common condition affecting millions of men worldwide. The pathophysiology and epidemiologic links between ED and risk factors for cardiovascular disease (CVD) are well-established. Lifestyle modifications such as smoking cessation, weight reduction, dietary modification, physical activity, and psychological stress reduction have been increasingly recognized as foundational to the prevention and treatment of ED. The aim of this review is to outline behavioral choices which may increase ones risk of developing ED, to present relevant studies addressing lifestyle factors correlated with ED, and to highlight proposed mechanisms for intervention aimed at improving erectile function in men with ED. These recommendations can provide a framework for counseling patients with ED about lifestyle modification. PMID:27141445

  16. Scorpion venom components that affect ion-channels function

    PubMed Central

    Quintero-Hernández, V.; Jiménez-Vargas, J.M.; Gurrola, G.B.; Valdivia, H.H.F.; Possani, L.D.

    2014-01-01

    SUMMARY The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na+-, K+- and Ca++-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are now adays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na+-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K+-channels are normally pore blocking agents. The Ryanodine Ca++-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells. PMID:23891887

  17. Functional roles affect diversity-succession relationships for boreal beetles.

    PubMed

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

  18. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.

  19. TLR4-Activated MAPK-IL-6 Axis Regulates Vascular Smooth Muscle Cell Function.

    PubMed

    Lee, Guan-Lin; Wu, Jing-Yiing; Tsai, Chien-Sung; Lin, Chih-Yuan; Tsai, Yi-Ting; Lin, Chin-Sheng; Wang, Yi-Fu; Yet, Shaw-Fang; Hsu, Yu-Juei; Kuo, Cheng-Chin

    2016-08-24

    Migration of vascular smooth muscle cells (VSMCs) into the intima is considered to be a vital event in the pathophysiology of atherosclerosis. Despite substantial evidence supporting the pathogenic role of Toll-like receptor 4 (TLR4) in the progression of atherogenesis, its function in the regulation of VSMC migration remains unclear. The goal of the present study was to elucidate the mechanism by which TLR4 regulates VSMC migration. Inhibitor experiments revealed that TLR4-induced IL-6 secretion and VSMC migration were mediated via the concerted actions of MyD88 and TRIF on the activation of p38 MAPK and ERK1/2 signaling. Neutralizing anti-IL-6 antibodies abrogated TLR4-driven VSMC migration and F-actin polymerization. Blockade of p38 MAPK or ERK1/2 signaling cascade inhibited TLR4 agonist-mediated activation of cAMP response element binding protein (CREB). Moreover, siRNA-mediated suppression of CREB production repressed TLR4-induced IL-6 production and VSMC migration. Rac-1 inhibitor suppressed TLR4-driven VSMC migration but not IL-6 production. Importantly, the serum level of IL-6 and TLR4 endogenous ligand HMGB1 was significantly higher in patients with coronary artery diseases (CAD) than in healthy subjects. Serum HMGB1 level was positively correlated with serum IL-6 level in CAD patients. The expression of both HMGB1 and IL-6 was clearly detected in the atherosclerotic tissue of the CAD patients. Additionally, there was a positive association between p-CREB and HMGB1 in mouse atherosclerotic tissue. Based on our findings, we concluded that, upon ligand binding, TLR4 activates p38 MAPK and ERK1/2 signaling through MyD88 and TRIF in VSMCs. These signaling pathways subsequently coordinate an additive augmentation of CREB-driven IL-6 production, which in turn triggers Rac-1-mediated actin cytoskeleton to promote VSMC migration.

  20. Acute effects of pomegranate extract on postprandial lipaemia, vascular function and blood pressure.

    PubMed

    Mathew, Aarati Susan; Capel-Williams, Gabriella M; Berry, Sarah E E; Hall, Wendy L

    2012-12-01

    We investigated whether a test drink enriched in pomegranate polyphenols, consumed with a high-fat meal, can reduce postprandial lipaemia and improve vascular function and blood pressure compared to placebo. Nineteen young, healthy men completed a randomized, controlled crossover trial. The active drink (containing a pomegranate extract) was consumed during a high-fat meal (ET-DUR) or 15 min before (ET-PRE), and the placebo drink (no pomegranate extract) was consumed during the high-fat meal (CONTROL). Postprandial lipaemia was assessed by venous plasma TAG 0-2 h, and capillary plasma TAG 0-4 h. Blood pressure and digital volume pulse, to measure reflection index (DVP-RI) and stiffness index (DVP-SI), were monitored at baseline, 2 and 4 h. There was no inhibition of postprandial lipaemia by the active drink compared to CONTROL. ET-PRE caused a greater increase in the venous plasma TAG at 2 h compared to CONTROL and ET-DUR (treatment effect P = 0.001). The incremental area under the curve 0-4 h for capillary plasma TAG was not significantly different between treatments. Systolic blood pressure (SBP) increased in the ET-PRE and ET-DUR groups to a lesser extent than the CONTROL group (treatment effect P = 0.041). There were no treatment effects for DVP-RI, DVP-SI or diastolic blood pressure. In conclusion, the consumption of a single drink containing ET-rich pomegranate extract did not decrease postprandial plasma TAG concentrations, but suppressed the postprandial increase in SBP following the high-fat meal.

  1. ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function

    PubMed Central

    Cui, Dan; Arima, Mitsuru; Takubo, Keiyo; Kimura, Tokuhiro; Horiuchi, Keisuke; Minagawa, Takuya; Matsuda, Satoshi; Ikeda, Eiji

    2015-01-01

    Neural vascular barrier is essential for the life of multicellular organisms, and its impairment by tissue hypoxia is known to be a central of pathophysiology accelerating the progression of various intractable neural diseases. Therefore, the molecules involved in hypoxia-induced impairment of vascular barrier can be the targets to establish new therapies for intractable diseases. Here, we demonstrate that a disintegrin and metalloproteinases (ADAMs) 12 and 17 expressed in endothelial cells are the molecules responsible for the impairment of neural vascular barrier by hypoxia. Brain microvascular endothelial cells in vitro lost their barrier properties immediately after hypoxic stimulation through diminished localization of claudin-5, a tight junction molecule, on cell membranes. Hypoxic disappearance of claudin-5 from cell membranes and the consequent loss of barrier properties were completely suppressed by inhibition of the metalloproteinase activity which was found to be attributed to ADAM12 and ADAM17. Inhibition of either ADAM12 or ADAM17 was sufficient to rescue the in vivo neural vasculature under hypoxia from the loss of barrier function. This is the first report to specify the molecules which are responsible for hypoxia-induced impairment of neural vascular barrier and furthermore can be the targets of new therapeutic strategies for intractable neural diseases. PMID:26242473

  2. ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function.

    PubMed

    Cui, Dan; Arima, Mitsuru; Takubo, Keiyo; Kimura, Tokuhiro; Horiuchi, Keisuke; Minagawa, Takuya; Matsuda, Satoshi; Ikeda, Eiji

    2015-08-05

    Neural vascular barrier is essential for the life of multicellular organisms, and its impairment by tissue hypoxia is known to be a central of pathophysiology accelerating the progression of various intractable neural diseases. Therefore, the molecules involved in hypoxia-induced impairment of vascular barrier can be the targets to establish new therapies for intractable diseases. Here, we demonstrate that a disintegrin and metalloproteinases (ADAMs) 12 and 17 expressed in endothelial cells are the molecules responsible for the impairment of neural vascular barrier by hypoxia. Brain microvascular endothelial cells in vitro lost their barrier properties immediately after hypoxic stimulation through diminished localization of claudin-5, a tight junction molecule, on cell membranes. Hypoxic disappearance of claudin-5 from cell membranes and the consequent loss of barrier properties were completely suppressed by inhibition of the metalloproteinase activity which was found to be attributed to ADAM12 and ADAM17. Inhibition of either ADAM12 or ADAM17 was sufficient to rescue the in vivo neural vasculature under hypoxia from the loss of barrier function. This is the first report to specify the molecules which are responsible for hypoxia-induced impairment of neural vascular barrier and furthermore can be the targets of new therapeutic strategies for intractable neural diseases.

  3. To what extent does urbanisation affect fragmented grassland functioning?

    PubMed

    van der Walt, L; Cilliers, S S; Kellner, K; Du Toit, M J; Tongway, D

    2015-03-15

    Urbanisation creates altered environments characterised by increased human habitation, impermeable surfaces, artificial structures, landscape fragmentation, habitat loss, resulting in different resource loss pathways. The vulnerable Rand Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa, has been extensively affected and transformed by urbanisation, agriculture, and mining. Grassland fragments in urban areas are often considered to be less species rich and less functional than in the more untransformed or "natural" exurban environments, and are therefore seldom a priority for conservation. Furthermore, urban grassland fragments are often being more intensely managed than exurban areas, such as consistent mowing in open urban areas. Four urbanisation measures acting as indicators for patterns and processes associated with urban areas were calculated for matrix areas surrounding each selected grassland fragment to quantify the position of each grassland remnant along an urbanisation gradient. The grassland fragments were objectively classified into two classes of urbanisation, namely "exurban" and "urban" based on the urbanisation measure values. Grazing was recorded in some exurban grasslands and mowing in some urban grassland fragments. Unmanaged grassland fragments were present in both urban and exurban areas. Fine-scale biophysical landscape function was determined by executing the Landscape Function Analysis (LFA) method. LFA assesses fine-scale landscape patchiness (entailing resource conserving potential and erosion resistance) and 11 soil surface indicators to produce three main LFA parameters (stability, infiltration, and nutrient cycling), which indicates how well a system is functioning in terms of fine-scale biophysical soil processes and characteristics. The aim of this study was to determine the effects of urbanisation and associated management practices on fine-scale biophysical landscape function of urban and exurban

  4. Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular Function in Chronic Tetraplegia

    PubMed Central

    La Fountaine, Michael F; Radulovic, Miroslav; Cardozo, Christopher P; Spungen, Ann M; DeMeersman, Ronald E; Bauman, William A

    2009-01-01

    Background/Objective: To improve our understanding of the lower-leg vascular responses of nitric oxide synthase inhibition in persons with tetraplegia. Participants: Six people with chronic tetraplegia and 6 age-matched controls. Methods: Lower-leg relative vascular resistance and venous volume variation were obtained by venous occlusion plethysmography and blood pressure by auscultation at baseline. Postintravenous infusion of the nitric oxide synthase inhibitor NG-nitro-l-arginine-methyl-ester (1 mg·kg−1) or placebo on separate days. Results: At baseline in the group with tetraplegia compared with controls, mean arterial pressure and relative vascular resistance of the leg were significantly lower. After nitric oxide synthase inhibition, mean arterial pressure and lower leg vascular resistance were significantly elevated in both groups. There were no group or intervention differences in venous volume variation. Conclusion: These preliminary results suggest that nitric oxide synthase inhibition with 1 mg·kg−1 NG-nitro-l-arginine-methyl-ester normalizes seated blood pressure and lower leg vascular resistance to control group baseline levels. PMID:20025149

  5. You're Only as Old as Your Arteries: Translational Strategies for Preserving Vascular Endothelial Function with Aging

    PubMed Central

    Kaplon, Rachelle E.; Gioscia-Ryan, Rachel A.; LaRocca, Thomas J.

    2014-01-01

    Endothelial dysfunction develops with age and increases the risk of age-associated vascular disorders. Nitric oxide insufficiency, oxidative stress, and chronic low-grade inflammation, induced by upregulation of adverse cellular signaling processes and imbalances in stress resistance pathways, mediate endothelial dysfunction with aging. Healthy lifestyle behaviors preserve endothelial function with aging by inhibiting these mechanisms, and novel nutraceutical compounds that favorably modulate these pathways hold promise as a complementary approach for preserving endothelial health. PMID:24985329

  6. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  7. Inhibition of vascular endothelial growth factor by small interfering RNA upregulates differentiation, maturation and function of dendritic cells

    PubMed Central

    WANG, HAIYAN; ZHANG, LUPING; ZHANG, SHAOYAN; LI, YANNIAN

    2015-01-01

    This study aimed to investigate the effects of vascular endothelial growth factor (VEGF) secreted by MCF-7 breast cancer cells on the differentiation, maturation and function of dendritic cells (DCs). Small interfering RNAs (siRNAs) directed against the VEGF gene were designed and transfected into MCF-7 breast cancer cells at an optimal concentration (100 nmol/l) using cationic liposome transfection reagent, whereas the control group was transfected with only transfection reagent. Western blot analysis and ELISA were used to determine VEGF protein expression and VEGF concentration, respectively. Mononuclear cells were cultured with the culture supernatants from primary MCF-7 cells (control group) and siRNA-treated MCF-7 cells (siRNA group). The DC phenotypes, including CD1a, CD80, CD83, CD86 and HLA-DR, were evaluated by flow cytometry. The MTT assay was used to assess the cytotoxicity of DC-mediated tumor-specific cytotoxic T lymphocytes (CTLs) against MCF-7 cells in the two different culture supernatants. The VEGF-targeted constructed siRNA inhibited VEGF expression in MCF-7 cells. Cultivation with the culture supernatants from MCF-7 cells treated with siRNA affected DC morphology. DCs in the siRNA group exhibited a significantly higher expression of CD86, CD80, CD83 and HLA-DR compared to the cells in the control group, whereas the expression of CD1a in the siRNA group was significantly lower compared to that in the control group. The cytotoxic activity of CTLs mediated by DCs was significantly altered by siRNA transfection. These results indicated that VEGF may play a significant role in tumor development, progression and immunosuppression. PMID:25452786

  8. The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

    PubMed Central

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Lustig, Susan; Yalavarthi, Srilakshmi; Parameswaran, Aishwarya; Brook, Robert D.; Kaplan, Mariana J.

    2013-01-01

    Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853. PMID:24252844

  9. Influences of maternal nutritional status on vascular function in the offspring.

    PubMed

    Poston, Lucilla

    2007-08-01

    Fetal growth restriction leading to low birthweight is associated with increased risk of ischaemic heart disease and hypertension in later life. Increasingly, it is recognised that cardiovascular risk may also be initiated in early life when the fetus and neonate are exposed to maternal nutritional excess. This review summarises the studies in man and animals that have investigated the potential role of vascular disorders in the aetiology of atherosclerosis and hypertension arising from early life nutritional deprivation or excess. Malfunction of the arterial endothelial cell layer in the offspring has been frequently described in association with both maternal under and overnutritional states and may play a permissive role in the origin of these disorders. Also prevalent is evidence for increased stiffness of the large arteries which may contribute to systolic hypertension. Further investigation is required into the intriguing suggestion that early life nutritional imbalance may adversely influence vascular angiogenesis leading to rarefaction and increased peripheral vascular resistance.

  10. PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.

    PubMed

    Zhang, Hao; Wang, Zheng; Feng, Shou-Jie; Xu, Lei; Shi, He-Xian; Chen, Li-Li; Yuan, Guang-Da; Yan, Wei; Zhuang, Wei; Zhang, Yi-Qian; Zhang, Zhong-Ming; Dong, Hong-Yan

    2015-03-11

    Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.

  11. Effect of short-term weight loss on the metabolic syndrome and conduit vascular endothelial function in overweight adults.

    PubMed

    Brook, Robert D; Bard, Robert L; Glazewski, Lynn; Kehrer, Christine; Bodary, Peter F; Eitzman, Daniel L; Rajagopalan, Sanjay

    2004-04-15

    Impaired vascular endothelial function may be an important mechanism linking obesity to increased cardiovascular risk. We investigated whether short-term weight loss improves conduit artery endothelial dysfunction in overweight adults. Forty-three otherwise healthy overweight patients with a body mass index > or =27 kg/m(2) completed an open-label 3-month trial consisting of a calorie-restricted diet and 120 mg of orlistat taken 3 times daily with meals. Endothelial function and parameters of the metabolic syndrome were measured before and after intervention. Subjects lost 6.6 +/- 3.4% of their body weight. Low-density lipoprotein cholesterol, low-density lipoprotein concentration, fasting insulin, and leptin decreased significantly (all p <0.009), and C-reactive protein decreased (p = 0.22). Conduit vascular function did not change as assessed by flow-mediated dilation (3.86 +/- 3.54 vs 3.74 +/- 3.78%, p = 0.86) and nitroglycerin-mediated dilation (17.18 +/- 5.89 vs 18.87 +/- 7.11%, p = 0.13) of the brachial artery. A moderate degree of weight reduction over 3 months improved the metabolic syndrome profile but not the vascular dysfunction associated with uncomplicated obesity.

  12. Functional Roles Affect Diversity-Succession Relationships for Boreal Beetles

    PubMed Central

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of “functional” groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience. PMID:23977350

  13. Does Bowel Preparation for Colonoscopy Affect Cognitive Function?

    PubMed Central

    Wadsworth, P.; Blackburne, H.; Dixon, L.; Dobbs, B.; Eglinton, T.; Ing, A.; Mulder, R.; Porter, R.J.; Wakeman, C.; Frizelle, F.A.

    2015-01-01

    Abstract Colonoscopy is a common procedure used in the diagnosis and treatment of a range of bowel disorders. Prior preparation involving potent laxatives is a necessary stage to ensure adequate visualization of the bowel wall. It is known that the sedatives given to most patients during the colonoscopy cause a temporary impairment in cognitive function; however, the potential for bowel preparation to affect cognitive function has not previously been investigated. To assess the effect of bowel preparation for colonoscopy on cognitive function. This was a prospective, nonrandomized controlled study of cognitive function in patients who had bowel preparation for colonoscopy compared with those having gastroscopy and therefore no bowel preparation. Cognitive function was assessed using the Modified Mini Mental State Examination (MMMSE) and selected tests from the Cambridge Neuropsychological Test Automated Battery. Individual test scores and changes between initial and subsequent tests were compared between the groups. Age, gender, and weight were also compared. Forty-three colonoscopy and 25 gastroscopy patients were recruited. The 2 groups were similar for age and gender; however, patients having gastroscopy were heavier. MMMSE scores for colonoscopy and gastroscopy groups, respectively, were 28.6 and 29.5 (P = 0.24) at baseline, 28.7 and 29.8 (P = 0.32) at test 2, 28.1 and 28.5 (P = 0.76) at test 3. Motor screening scores for colonoscopy and gastroscopy groups, respectively, were 349.3 and 354.1 (P = 0.97) at baseline, 307.5 and 199.7 (P = 0.06) at test 2, 212.0 and 183.2 (P = 0.33) at test 3. Spatial working memory scores for colonoscopy and gastroscopy groups, respectively, were 14.4 and 6.7 (P = 0.29) at baseline, 9.7 and 4.3 (P = 0.27) at test 2, 10 and 4.5 (P = 0.33) at test 3. Digit Symbol Substitution Test scores for colonoscopy and gastroscopy groups, respectively, were 36.3 and 37.8 (P = 0.84) at baseline, 36.4 and

  14. Vascular function assessed by passive leg movement and flow-mediated dilation: initial evidence of construct validity.

    PubMed

    Rossman, Matthew J; Groot, H Jonathan; Garten, Ryan S; Witman, Melissa A H; Richardson, Russell S

    2016-11-01

    The vasodilatory response to passive leg movement (PLM) appears to provide a novel, noninvasive assessment of vascular function. However, PLM has yet to be compared with the established noninvasive assessment of vascular health, flow-mediated dilation (FMD). Therefore, as an initial evaluation of the construct validity of PLM and upright seated and supine PLM as well as brachial (BA) and superficial femoral (SFA) artery FMDs were performed in 10 young (22 ± 1) and 30 old (73 ± 2) subjects. During upright seated PLM, the peak change in leg blood flow (ΔLBF) and leg vascular conductance (ΔLVC) was significantly correlated with BA (r = 0.57 and r = 0.66) and SFA (r = 0.44 and r = 0.41, ΔLBF and ΔLVC, respectively) FMD. Furthermore, although the relationships were not as strong, the supine PLM response was also significantly correlated with BA (r = 0.38 and r = 0.35) and SFA (r = 0.39 and r = 0.35, ΔLBF and ΔLVC, respectively) FMD. Examination of the young and old separately, however, revealed that significant relationships persisted in both groups only for the upright seated PLM response and BA FMD (young: r = 0.73 and r = 0.77; old: r = 0.35 and r = 0.45, ΔLBF and ΔLVC, respectively). Normalizing FMD for shear rate during PLM abrogated all significant relationships between the PLM and FMD response, suggesting a role for nitric oxide (NO) in these associations. Collectively, these data indicate that PLM, particularly upright seated PLM, likely provides an index of vascular health analogous to the traditional FMD test. Given the relative ease of PLM implementation, these data have important positive implications for PLM as a clinical vascular health assessment.

  15. Salvianolic acid B improves vascular endothelial function in diabetic rats with blood glucose fluctuations via suppression of endothelial cell apoptosis.

    PubMed

    Ren, Younan; Tao, Shanjun; Zheng, Shuguo; Zhao, Mengqiu; Zhu, Yuanmei; Yang, Jieren; Wu, Yuanjie

    2016-11-15

    Vascular endothelial cell injury is an initial event in atherosclerosis. Salvianolic acid B (Sal B), a main bioactive component in the root of Salvia miltiorrhiza, has vascular protective effect in diabetes, but the underlying mechanisms remain unclear. The present study investigated the effect of Sal B on vascular endothelial function in diabetic rats with blood glucose fluctuations and the possible mechanisms implicated. The results showed that diabetic rats developed marked endothelial dysfunction as exhibited by impaired acetylcholine induced vasodilation. Supplementation with Sal B resulted in an evident improvement of endothelial function. Phosphorylation (Ser 1177) of endothelial nitric oxide synthase (eNOS) was significantly restored in Sal B treated diabetic rats, accompanied by an evident recovery of NO metabolites. Sal B effectively reduced vascular endothelial cell apoptosis, with Bcl-2 protein up-regulated and Bax protein down-regulated markedly. Treatment with Sal B led to an evident amelioration of oxidative stress in diabetic rats as manifested by enhanced antioxidant capacity and decreased contents of malondialdehyde in aortas. Protein levels of NOX2 and NOX4, two main isoforms of NADPH oxidase known as the major source of reactive oxygen species in the vasculature, were markedly decreased in Sal B treated groups. In addition, treatment with Sal B led to an evident decrease of serum lipids. Taken together, this study indicates that Sal B is capable of improving endothelial function in diabetic rats with blood glucose fluctuations, of which the underlying mechanisms might be related to suppression of endothelial cell apoptosis and stimulation of eNOS phosphorylation (Ser 1177).

  16. Effects of sodium nitrite supplementation on vascular function and related small metabolite signatures in middle-aged and older adults

    PubMed Central

    Johnson, Lawrence C.; Brooks, Forrest A.; Evans, Trent D.; Justice, Jamie N.; Cruickshank-Quinn, Charmion; Reisdorph, Nichole; Bryan, Nathan S.; McQueen, Matthew B.; Santos-Parker, Jessica R.; Chonchol, Michel B.; Bassett, Candace J.; Sindler, Amy L.; Giordano, Tony; Seals, Douglas R.

    2015-01-01

    Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction and arterial stiffening with aging. Supplementation with sodium nitrite, a precursor of NO, ameliorates age-related vascular endothelial dysfunction and arterial stiffness in mice, but effects on humans, including the metabolic pathways altered, are unknown. The purpose of this study was to determine the safety, feasibility, and efficacy of oral sodium nitrite supplementation for improving vascular function in middle-aged and older adults and to identify related circulating metabolites. Ten weeks of sodium nitrite (80 or 160 mg/day, capsules, TheraVasc; randomized, placebo control, double blind) increased plasma nitrite acutely (5- to 15-fold, P < 0.001 vs. placebo) and chronically (P < 0.10) and was well tolerated without symptomatic hypotension or clinically relevant elevations in blood methemoglobin. Endothelial function, measured by brachial artery flow-mediated dilation, increased 45-60% vs. baseline (P < 0.10) without changes in body mass or blood lipids. Measures of carotid artery elasticity (ultrasound and applanation tonometry) improved (decreased β-stiffness index, increased cross-sectional compliance, P < 0.05) without changes in brachial or carotid artery blood pressure. Aortic pulse wave velocity was unchanged. Nitrite-induced changes in vascular measures were significantly related to 11 plasma metabolites identified by untargeted analysis. Baseline abundance of multiple metabolites, including glycerophospholipids and fatty acyls, predicted vascular changes with nitrite. This study provides evidence that sodium nitrite supplementation is well tolerated, increases plasma nitrite concentrations, improves endothelial function, and lessens carotid artery stiffening in middle-aged and older adults, perhaps by altering multiple metabolic pathways, thereby warranting a larger clinical trial. PMID:26607249

  17. Tie-dyed2 encodes a callose synthase that functions in vein development and affects symplastic trafficking within the phloem of maize leaves.

    PubMed

    Slewinski, Thomas L; Baker, R Frank; Stubert, Adam; Braun, David M

    2012-11-01

    The tie-dyed2 (tdy2) mutant of maize (Zea mays) displays variegated green and yellow leaves. Intriguingly, the yellow leaf tissues hyperaccumulate starch and sucrose, the soluble sugar transported long distance through the phloem of veins. To determine the molecular basis for Tdy2 function, we cloned the gene and found that Tdy2 encodes a callose synthase. RNA in situ hybridizations revealed that in developing leaves, Tdy2 was most highly expressed in the vascular tissue. Comparative expression analysis with the vascular marker maize PINFORMED1a-yellow fluorescent protein confirmed that Tdy2 was expressed in developing vein tissues. To ascertain whether the defect in tdy2 leaves affected the movement of sucrose into the phloem or its long-distance transport, we performed radiolabeled and fluorescent dye tracer assays. The results showed that tdy2 yellow leaf regions were defective in phloem export but competent in long-distance transport. Furthermore, transmission electron microscopy of tdy2 yellow leaf regions showed incomplete vascular differentiation and implicated a defect in cell-to-cell solute movement between phloem companion cells and sieve elements. The disruption of sucrose movement in the phloem in tdy2 mutants provides evidence that the Tdy2 callose synthase functions in vascular maturation and that the vascular defects result in impaired symplastic trafficking into the phloem translocation stream.

  18. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study.

    PubMed

    Bruder-Nascimento, Thiago; Campos, Dijon Henrique Salome

    2015-01-23

    Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)Fundamento: Estresse está associado com complicações cardiovasculares. Objetivos: O objetivo do presente estudo foi avaliar se o estresse crônico induz alterações vasculares, e se essas alterações são dependentes de óxido nítrico (NO) e Ca2+. Métodos: Ratos machos Wistar com 30 dias de idade foram separados em 2 grupos: controle (C) e Estresse (St). Utilizou-se estresse crônico de imobilização por 1 hora/dia, 5 dias/semana, 15 semanas. Pressão arterial sistólica foi avaliada. A função vascular foi

  19. Thigh muscle size and vascular function after blood flow-restricted elastic band training in older women

    PubMed Central

    Yasuda, Tomohiro; Fukumura, Kazuya; Tomaru, Takanobu; Nakajima, Toshiaki

    2016-01-01

    We examined the effect of elastic band training with blood flow restriction (BFR) on thigh muscle size and vascular function in older women. Older women were divided into three groups: low-intensity elastic band BFR training (BFR-Tr, n = 10), middleto high-intensity elastic band training (MH-Tr, n = 10), and no training (Ctrl, n = 10) groups. BFR-Tr and MH-Tr groups performed squat and knee extension exercises using elastic band, 2 days/week for 12 weeks. During BFR-Tr exercise session, subjects wore pressure cuffs around the most proximal region of both thighs. The following measurements were taken before (pre) and 3-5 days after (post) the final training session: MRI-measured muscle cross-sectional area (CSA) at mid-thigh, maximum voluntary isometric contraction (MVIC) of knee extension, central systolic blood pressure (c-SBP), central-augmentation index (c-AIx), cardio-ankle vascular index testing (CAVI), ankle-brachial pressure index (ABI). Quadriceps muscle CSA (6.9%) and knee extension MVIC (13.7%) were increased (p < 0.05) in the BFR-Tr group, but not in the MH-Tr and the Ctrl groups. Regarding c-SBP, c-AIx, CAVI and ABI, there were no changes between pre- and post- results among the three groups. Elastic band BFR training increases thigh muscle CSA as well as maximal muscle strength, but does not decrease vascular function in older women. PMID:27244884

  20. Endothelial Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Is Critical for Lymphatic Vascular Development and Function

    PubMed Central

    Guo, Chang-An; Danai, Laura V.; Yawe, Joseph C.; Gujja, Sharvari; Edwards, Yvonne J. K.

    2016-01-01

    The molecular mechanisms underlying lymphatic vascular development and function are not well understood. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and atherosclerosis. Here, we show that constitutive loss of EC Map4k4 in mice causes postnatal lethality due to chylothorax, suggesting that Map4k4 is required for normal lymphatic vascular function. Mice constitutively lacking EC Map4k4 displayed dilated lymphatic capillaries, insufficient lymphatic valves, and impaired lymphatic flow; furthermore, primary ECs derived from these animals displayed enhanced proliferation compared with controls. Yeast 2-hybrid analyses identified the Ras GTPase-activating protein Rasa1, a known regulator of lymphatic development and lymphatic endothelial cell fate, as a direct interacting partner for Map4k4. Map4k4 silencing in ECs enhanced basal Ras and extracellular signal-regulated kinase (Erk) activities, and primary ECs lacking Map4k4 displayed enhanced lymphatic EC marker expression. Taken together, these results reveal that EC Map4k4 is critical for lymphatic vascular development by regulating EC quiescence and lymphatic EC fate. PMID:27044870

  1. Catechin averts experimental diabetes mellitus-induced vascular endothelial structural and functional abnormalities.

    PubMed

    Bhardwaj, Pooja; Khanna, Deepa; Balakumar, Pitchai

    2014-03-01

    Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED), an initial event that could lead to the pathogenesis of atherosclerosis and hypertension. Previous studies showed that catechin, a key component of green tea, possesses vascular beneficial effects. We investigated the effect of catechin hydrate in diabetes mellitus-induced experimental vascular endothelial abnormalities (VEA). Streptozotocin (50 mg/kg, i.p., once) administration to rats produced diabetes mellitus, which subsequently induced VEA in 8 weeks by markedly attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentrations and impairing aortic endothelial integrity. These abnormalities in diabetic rats were accompanied with elevated aortic superoxide anion generation and serum lipid peroxidation in addition to hyperglycemia. Catechin hydrate treatment (50 mg/kg/day p.o., 3 weeks) markedly prevented diabetes mellitus-induced VEA and vascular oxidative stress. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase, or Wortmannin (100 nM), a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), markedly prevented catechin hydrate-induced improvement in acetylcholine-provoked endothelium-dependent relaxation in the diabetic rat aorta. Moreover, catechin hydrate treatment considerably reduced the elevated level of serum glucose in diabetic rats. In conclusion, catechin hydrate treatment prevents diabetes mellitus-induced VED through the activation of endothelial PI3K signal and subsequent activation of eNOS and generation of nitric oxide. In addition, reduction in high glucose, vascular oxidative stress, and lipid peroxidation might additionally contribute to catechin hydrate-associated prevention of diabetic VEA.

  2. Effects of Acute Exposure to Moderate Altitude on Vascular Function, Metabolism and Systemic Inflammation

    PubMed Central

    Stöwhas, Anne-Christin; Latshang, Tsogyal D.; Lo Cascio, Christian M.; Lautwein, Sina; Stadelmann, Katrin; Tesler, Noemi; Ayers, Lisa; Berneis, Kaspar; Gerber, Philipp A.; Huber, Reto; Achermann, Peter; Bloch, Konrad E.; Kohler, Malcolm

    2013-01-01

    Background Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. Objectives To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. Methods In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. Results Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides −0.14 mmol/l, p = 0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio −0.25, p = 0.001), LDL particle size increased (median difference +0.45 nm, p = 0.048) and hsCRP decreased (median difference −0.18 mg/l, p = 0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. Conclusions Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. Trial Registration ClinicalTrials.gov NCT01130948 PMID:23936377

  3. Maternal metabolic stress may affect oviduct gatekeeper function.

    PubMed

    Jordaens, Lies; Van Hoeck, Veerle; Maillo, Veronica; Gutierrez-Adan, Alfonso; Marei, Waleed Fawzy A; Vlaeminck, Bruno; Thys, Sofie; Sturmey, Roger G S; Bols, Peter; Leroy, Jo

    2017-03-03

    We hypothesized that elevated non-esterified fatty acids (NEFA) modify in vitro bovine oviduct epithelial cell (BOEC) metabolism and barrier function. Hereto, BOECs were studied in a polarized system with 24h-treatments at day 9: 1) CONTROL (0µM NEFA + 0%EtOH), 2) SOLVENT CONTROL (0µM NEFA + 0.45%EtOH), 3) BASAL NEFA (720µM NEFA + 0.45%EtOH in the basal compartment), 4) APICAL NEFA (720µM NEFA + 0.45%EtOH in the apical compartment). FITC-albumin was used for monolayer permeability assessment, and related to Transepithelial Electric Resistance (TER). Fatty acid (FA), glucose, lactate and pyruvate concentrations were measured in spent medium. Intracellular lipid droplets (LD) and FA-uptake were studied using Bodipy 493/503 and immunolabelling of FA-transporters (FAT/CD36, FABP3 and caveolin1). BOEC-mRNA was retrieved for qRT-PCR. Results revealed that APICAL NEFA reduced relative TER-increase (46.85%) during treatment, and increased FITC-albumin flux (27.59%) compared to other treatments. In BASAL NEFA, FAs were transferred to the apical compartment as free FAs: mostly palmitic and oleic acid increased, respectively 56.0 % and 33.5% of initial FA-concentrations. APICAL NEFA allowed no FA-transfer, but induced LD-accumulation and upregulated FA-transporter expression (↑CD36, ↑FABP3, ↑CAV1-protein-expression). Gene expression in APICAL NEFA indicated increased anti-apoptotic (↑BCL2) and anti-oxidative (↑SOD1) capacity, upregulated lipid metabolism (↑CPT1, ↑ACSL1 and ↓ACACA), and FA-uptake (↑CAV1). All treatments had similar carbohydrate metabolism and oviduct function specific gene expression (=OVGP1, ESR1, FOXJ1). Overall, elevated NEFAs affected BOEC-metabolism and barrier function differently depending on NEFA-exposure side. Data substantiate the concept of the oviduct as a gatekeeper that may actively alter early embryonic developmental conditions.

  4. Aldosterone and the vascular system.

    PubMed

    Cachofeiro, Victoria; Miana, Maria; de Las Heras, Natalia; Martín-Fernández, Beatriz; Ballesteros, Sandra; Fernández-Tresguerres, Jesús; Lahera, Vicente

    2008-04-01

    Aldosterone can act in different tissues exerting physiological and pathological effects. At the vascular level, aldosterone affects endothelial function since administration of aldosterone impaired endothelium-dependent relaxations. In addition, the administration of mineralocorticoid receptor antagonists ameliorate relaxation to acetylcholine in models of both hypertension and atherosclerosis and in patients with heart failure. A reduction in nitric oxide levels seems to be the main mechanism underlying this effect due to a reduction in its production as well as an increase in its degradation by reactive oxygen species. Aldosterone is a pro-inflammatory factor that can participate in the vascular inflammatory process associated with different pathologies including hypertension through activation of the NFkappaB system, which mediates the vascular production of different cytokines. This mineralocorticoid also participates in the vascular remodeling observed in hypertensive rats since the administration of eplerenone improved the media-to-lumen ratio in these animals. This effect seems to be due to an increase in extracellular matrix. In summary, aldosterone through mineralocorticoid receptors can participate in the vascular damage associated with different pathologies including hypertension through its prooxidant, pro-inflammatory and profibrotic effects that triggered endothelial dysfunction, an inflammatory process and vascular remodeling.

  5. Di-peptidyl peptidase-4 inhibitor sitagliptin protects vascular function in metabolic syndrome: possible role of epigenetic regulation.

    PubMed

    Cicek, Figen Amber; Amber, Cicek Figen; Tokcaer-Keskin, Zeynep; Zeynep, Tokcaer-Keskin; Ozcinar, Evren; Evren, Ozcinar; Bozkus, Yosuf; Yusuf, Bozkus; Akcali, Kamil Can; Can, Akcali Kamil; Turan, Belma; Belma, Turan

    2014-08-01

    Metabolic syndrome (MetS) is a complex medical disorder characterized by insulin resistance, hypertension, and high risk of coronary disease and stroke. Microvascular rarefaction and endothelial dysfunction have also been linked with MetS, and recent evidence from clinical studies supports the efficacy of incretin-based antidiabetic therapies for vascular protection in diabetes. Previous studies pointed out the importance of dipeptidyl peptidase-4 (DPP-4) inhibition in endothelial cells due to getting protection against metabolic pathologies. We therefore aimed to investigate the acute effects of a DPP-4 inhibitor, sitagliptin, on vascular function in rats with high-sucrose diet-induced MetS. In order to elucidate the mechanisms implicated in the effects of DPP-4 inhibition, we tested the involvement of NO pathway and epigenetic regulation in the MetS. Acute use of sitagliptin protects the vascular function in the rats with MetS in part due to NO pathway via restoring the depressed aortic relaxation responses mediated by receptors. Application of sitagliptin enhanced the depressed phosphorylation levels of both the endothelial NO synthase and the apoptotic status of protein kinase B, known as Akt, in endothelium-intact thoracic aorta from rats with MetS. One-hour application of sitagliptin on aortic rings from rats with MetS also induced remarkable histon posttranslational modifications such as increased expression of H3K27Me3, but not of H3K27Me2, resulting in an accumulation of the H3K27Me3. Our findings suggest that, in addition to its well-known hypoglycemic action, sitagliptin may also have beneficial effects on hyperglycemia-induced vascular changes in an endotheium-dependent manner. These present results with sitagliptin aside from the glycaemic control, may demonstrate its important role in the treatment of patients with MetS.

  6. Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep

    PubMed Central

    Volk, Kenneth A.; Roghair, Robert D.; Jung, Felicia; Scholz, Thomas D.; Lamb, Fred S.

    2010-01-01

    Exposure of the early-gestation ovine fetus to exogenous glucocorticoids induces changes in postnatal cardiovascular physiology. We sought to characterize coronary artery vascular function in this model by elucidating the contribution of nitric oxide and reactive oxygen species to altered coronary vascular reactivity and examining the proliferative potential of coronary artery vascular smooth muscle cells. Dexamethasone (dex, 0.28 mg·kg−1·day−1 for 48 h) was administered to pregnant ewes at 27–28-day gestation (term 145 days). Coronary arteries were isolated from 1- to 2-wk-old dex-exposed offspring and aged-matched controls. Compared with controls, coronary arteries from dex-exposed lambs demonstrated enhanced vasoconstriction to endothelin-1 and ACh that was abolished by endothelial removal or preincubation with the nitric oxide synthase inhibitor l-NNA, membrane-permeable superoxide dismutase + catalase, or apamin + charybdotoxin, but not indomethacin. The rate of coronary vascular smooth muscle cell (VSMC) proliferation was also significantly greater in dex-exposed lambs. Protein levels of the proliferating cell nuclear antigen were increased and α-smooth muscle actin decreased in dex-exposed coronary VSMC, consistent with a proliferative state. Finally, expression of the NADPH oxidase Nox 4, but not Nox 1, mRNA was also decreased in coronary VSMC from dex-exposed lambs. These findings suggest an important interaction exists between early-gestation glucocorticoid exposure and reactive oxygen species that is associated with alterations in endothelial function and coronary VSMC proliferation. These changes in coronary physiology are consistent with those associated with the development of atherosclerosis and may provide an important link between an adverse intrauterine environment and increased risk for coronary artery disease. PMID:20335378

  7. Complementary interplay between matrix metalloproteinase-9, vascular endothelial growth factor and osteoclast function drives endochondral bone formation

    PubMed Central

    Ortega, Nathalie; Wang, Ke; Ferrara, Napoleone; Werb, Zena; Vu, Thiennu H.

    2010-01-01

    SUMMARY Long bone development depends on endochondral bone formation, a complex process requiring exquisite balance between hypertrophic cartilage (HC) formation and its ossification. Dysregulation of this process may result in skeletal dysplasias and heterotopic ossification. Endochondral ossification requires the precise orchestration of HC vascularization, extracellular matrix remodeling, and the recruitment of osteoclasts and osteoblasts. Matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and osteoclasts have all been shown to regulate endochondral ossification, but how their function interrelates is not known. We have investigated the functional relationship among these regulators of endochondral ossification, demonstrating that they have complementary but non-overlapping functions. MMP-9, VEGF and osteoclast deficiency all cause impaired growth plate ossification resulting in the accumulation of HC. VEGF mRNA and protein expression are increased at the MMP-9−/− growth plate, and VEGF activity contributes to endochondral ossification since sequestration of VEGF by soluble receptors results in further inhibition of growth plate vascularization and ossification. However, VEGF bioavailability is still limited in MMP-9 deficiency, as exogenous VEGF is able to rescue the MMP-9−/− phenotype, demonstrating that MMP-9 may partially, but not fully, regulate VEGF bioavailability. The organization of the HC extracellular matrix at the MMP-9−/− growth plate is altered, supporting a role for MMP-9 in HC remodeling. Inhibition of VEGF impairs osteoclast recruitment, whereas MMP-9 deficiency leads to an accumulation of osteoclasts at the chondro-osseous junction. Growth plate ossification in osteoclast-deficient mice is impaired in the presence of normal MMP-9 expression, indicating that other osteoclastic functions are also necessary. Our data delineate the complementary interplay between MMP-9, VEGF and osteoclast function that is

  8. Dietary supplementation of yucca (Yucca schidigera) affects ovine ovarian functions.

    PubMed

    Vlčková, Radoslava; Sopková, Drahomíra; Andrejčáková, Zuzana; Valocký, Igor; Kádasi, Attila; Harrath, Abdel Halim; Petrilla, Vladimír; Sirotkin, Alexander V

    2017-01-15

    Yucca (Yucca schidigera) is a popular medicinal plant due to its many positive effects on animal and human physiology, including their reproductive systems. To examine the effect of supplemental yucca feeding on sheep reproduction, including ovarian functions and their hormonal regulators, ewes were fed (or not fed, control) yucca powder (1.5 g/head/day, 30 days). Macromorphometric indexes of the oviduct, ovary, and ovarian folliculogenesis were measured. Reproductive hormone levels in the blood were measured using a radioimmunoassay. Granulosa cells were aspirated from the ovary, and their proliferation and apoptosis were detected using immunocytochemistry. To assess secretory activity and its response to gonadotropin, ovarian fragments of treated and control ewes were cultured with and without follicle-stimulating hormone (FSH; 0, 0.1, 1, 10, or 100 IU/mL), and the release of reproductive hormones into the culture medium was evaluated. Finally, to examine the direct action of yucca on the ovary, ovarian fragments from control ewes were cultured with and without yucca extract (1, 10, or 100 μg/mL), and the release of reproductive hormones was measured. Yucca supplementation significantly decreased the size of small antral follicles (2 to <5 mm in diameter), increased accumulation of the apoptosis marker bax, and decreased serum progesterone (P4) and estradiol (E2) levels. It inhibited the release of P4 (but not other hormones), to prevent the stimulatory action of FSH on P4 output and promoted insulin-like growth factor I (IGF-I) release by fragments cultured with FSH. However, yucca supplementation did not affect the size of larger follicles and number of follicles, volume and weight of ovaries, length and weight of oviducts, caspase 3 accumulation, cell proliferation, testosterone (T) or IGF-I serum levels, or T or E2 release by cultured ovarian fragments and their response to FSH. Yucca addition to culture medium inhibited P4 and IGF-I, but not T or E2

  9. Coaxial electrospinning multicomponent functional controlled-release vascular graft: Optimization of graft properties.

    PubMed

    Yin, Anlin; Luo, Rifang; Li, Jiukai; Mo, Xiumei; Wang, Yunbing; Zhang, Xingdong

    2017-04-01

    Small diameter vascular grafts possessing desirable biocompatibility and suitable mechanical properties have become an urgent clinic demand. Herein, heparin loaded fibrous grafts of collagen/chitosan/poly(l-lactic acid-co-ε-caprolactone) (PLCL) were successfully fabricated via coaxial electrospinning. By controlling the concentration of heparin and the ratio of collagen/chitosan/PLCL, most grafts had the heparin encapsulation efficiency higher than 70%, and the heparin presented sustained release for more than 45 days. Particularly, such multicomponent grafts had relative low initial burst release, and after heparin releasing for 3 weeks, the grafts still showed good anti-platelet adhesion ability. In addition, along with the excellent cell biocompatibility, the fabricated grafts possessed suitable mechanical properties including good tensile strength, suture retention strength, burst pressure and compliance which could well match the native blood vessels. Thus, the optimized graft properties could be properly addressed for vascular tissue application via coaxial electrospinning.

  10. Perivascular adipose tissue in vascular function and disease: a review of current research and animal models.

    PubMed

    Brown, Nicholas K; Zhou, Zhou; Zhang, Jifeng; Zeng, Rong; Wu, Jiarui; Eitzman, Daniel T; Chen, Y Eugene; Chang, Lin

    2014-08-01

    Perivascular adipose tissue (PVAT), long assumed to be nothing more than vessel-supporting connective tissue, is now understood to be an important, active component of the vasculature, with integral roles in vascular health and disease. PVAT is an adipose tissue with similarities to both brown and white adipose tissue, although recent evidence suggests that PVAT develops from its own precursors. Like other adipose tissue depots, PVAT secretes numerous biologically active substances that can act in both autocrine and paracrine fashion. PVAT has also proven to be involved in vascular inflammation. Although PVAT can support inflammation during atherosclerosis via macrophage accumulation, emerging evidence suggests that PVAT also has antiatherosclerotic properties related to its abilities to induce nonshivering thermogenesis and metabolize fatty acids. We here discuss the accumulated knowledge of PVAT biology and related research on models of hypertension and atherosclerosis.

  11. Elementary Ca2+ Signals Through Endothelial TRPV4 Channels Regulate Vascular Function

    PubMed Central

    Sonkusare, Swapnil K.; Bonev, Adrian D.; Ledoux, Jonathan; Liedtke, Wolfgang; Kotlikoff, Michael I.; Heppner, Thomas J.; Hill-Eubanks, David C.; Nelson, Mark T.

    2013-01-01

    Major features of the transcellular signaling mechanism responsible for endothelium-dependent regulation of vascular smooth muscle tone are unresolved. We identified local calcium (Ca2+) signals (“sparklets”) in the vascular endothelium of resistance arteries that represent Ca2+ influx through single TRPV4 cation channels. Gating of individual TRPV4 channels within a four-channel cluster was cooperative, with activation of as few as three channels per cell causing maximal dilation through activation of endothelial cell intermediate (IK)- and small (SK)-conductance, Ca2+-sensitive potassium (K+) channels. Endothelial-dependent muscarinic receptor signaling also acted largely through TRPV4 sparklet-mediated stimulation of IK and SK channels to promote vasodilation. These results support the concept that Ca2+ influx through single TRPV4 channels is leveraged by the amplifier effect of cooperative channel gating and the high Ca2+ sensitivity of IK and SK channels to cause vasodilation. PMID:22556255

  12. TGF-β Is Required for Vascular Barrier Function, Endothelial Survival and Homeostasis of the Adult Microvasculature

    PubMed Central

    Maharaj, Arindel S. R.; Sekiyama, Eiichi; Maldonado, Angel E.; D'Amore, Patricia A.

    2009-01-01

    Pericyte-endothelial cell (EC) interactions are critical to both vascular development and vessel stability. We have previously shown that TGF-β signaling between EC and mural cells participates in vessel stabilization in vitro. We therefore investigated the role of TGF-β signaling in maintaining microvessel structure and function in the adult mouse retinal microvasculature. TGF-β signaling was inhibited by systemic expression of soluble endoglin (sEng) and inhibition was demonstrated by reduced phospho-smad2 in the adult retina. Blockade of TGF-β signaling led to increased vascular and neural cell apoptosis in the retina, which was associated with decreased retinal function, as measured by electroretinogram (ERG). Perfusion of the inner retinal vasculature was impaired and was accompanied by defective autoregulation and loss of capillary integrity. Fundus angiography and Evans blue permeability assay revealed a breakdown of the blood-retinal-barrier that was characterized by decreased association between the tight junction proteins zo-1 and occludin. Inhibition of TGF-β signaling in cocultures of EC and 10T1/2 cells corroborated the in vivo findings, with impaired EC barrier function, dissociation of EC from 10T1/2 cells, and endothelial cell death, supporting the role of EC-mesenchymal interactions in TGF-β signaling. These results implicate constitutive TGF-β signaling in maintaining the integrity and function of the adult microvasculature and shed light on the potential role of TGF-β signaling in vasoproliferative and vascular degenerative retinal diseases. PMID:19340291

  13. Arterial wall mechanics as a function of heart rate: role of vascular smooth muscle

    NASA Astrophysics Data System (ADS)

    Salvucci, Fernando Pablo; Schiavone, Jonathan; Craiem, Damian; Barra, Juan Gabriel

    2007-11-01

    Vascular wall viscoelasticity can be evaluated using a first-order lumped model. This model consists of a spring with elastic constant E and a dashpot with viscous constant η. More importantly, this viscoelastic model can be fitted in-vivo measuring arterial pressure and diameter. The aim of this work is to analyze the influence of heart rate over E and η. In two anesthetized sheep, diameter in thoracic aorta and intravascular pressure has been registered. The right atrium was connected to a programmable stimulator through a pair of pace-maker wires to produce changes in stimulation heart rate (HR) from 80 to 160 bpm. Additionally, local activation of vascular smooth muscle was induced with phenylephrine. After converting pressure and diameter signals into stress and strain respectively, E y η were calculated in control state and during muscle activation. The elastic modulus E did not present significant changes with heart rate. The viscous modulus η decreased 49% with a two-fold acceleration in heart rate from 80 to 160 bpm. However, the product η HR remained stable. The viscous modulus η increased 39% with smooth muscle activation. No significant pressure changes were registered during the experiment. The contractile action of vascular smooth muscle could contribute to increasing arterial wall viscosity. The decrease of η when HR increased might be related to smooth muscle relaxation mediated by endothelium activity, which was stimulated by flow increase. We conclude that HR can modulate arterial wall viscoelasticity through endothelium-dependent mechanisms.

  14. Obstructive sleep apnea syndrome, vascular pathology, endothelial function and endothelial cells and circulating microparticles.

    PubMed

    Stiefel, Pablo; Sánchez-Armengol, Maria Angeles; Villar, José; Vallejo-Vaz, Antonio; Moreno-Luna, Rafael; Capote, Francisco

    2013-08-01

    Accelerated atherosclerosis and increased cardiovascular risk are frequently reported in patients with obstructive sleep apnea (OSA) syndrome. In this article the authors attempt a review of the current understanding of the relationship between vascular risk and OSA syndrome based on large cohort studies that related the disease to several cardiovascular risk factors and vascular pathologies. We also discuss the pathophysiological mechanisms that may be involved in this relationship, starting with endothelial dysfunction and its mediators. These include an increased oxidative stress and inflammation as well as several disorders of coagulation and lipid metabolism. Moreover, circulating microparticles from activated leukocytes (CD62L_MPs) are higher in patients with OSA and there is a positive correlation between circulating levels of CD62L_MPs and nocturnal hypoxemia severity. Finally, circulating level of endothelial microparticles and circulating endothelial cells seem to be increased in patients with OSA. Also, endothelial progenitor cells are reduced and plasma levels of the vascular endothelial growth factor are increased.

  15. 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.

  16. Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood–brain barrier function in mice

    PubMed Central

    Alata, Wael; Ye, Yue; St-Amour, Isabelle; Vandal, Milène; Calon, Frédéric

    2015-01-01

    Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood–brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [3H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [3H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development. PMID:25335802

  17. Vascular Function, Cerebral Cortical Thickness, and Cognitive Performance in Middle-Aged Hispanic and Non-Hispanic Caucasian Adults

    PubMed Central

    Pasha, Evan; Kaur, Sonya S.; Gonzales, Mitzi M.; Machin, Daniel R.; Kasischke, Kennon; Tanaka, Hirofumi; Haley, Andreana P.

    2015-01-01

    Hispanics are at increased risk of acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health to measures of cerebral gray matter integrity, 60 middle-aged Hispanic and non-Hispanic Caucasian participants were matched across age, gender, years of education, and mental status. Arterial stiffness was characterized via β-stiffness index and carotid-femoral pulse-wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non-Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (p=0.04) with concurrently lower language (p=0.02), memory (p=0.03), and attention-executive functioning (p=0.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics. PMID:25720950

  18. 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

  19. Assessment of in vivo fetal growth and placental vascular function in a novel intrauterine growth restriction model of progressive uterine artery occlusion in guinea pigs

    PubMed Central

    Herrera, Emilio A.; Alegría, René; Farias, Marcelo; Díaz‐López, Farah; Hernández, Cherie; Uauy, Ricardo; Regnault, Timothy R. H.; Casanello, Paola

    2016-01-01

    Key points Intrauterine growth restriction (IUGR) is associated with short‐ and long‐term detrimental cardiometabolic effects.Mice and rats are commonly used to assess IUGR, but differences in placental and fetal developmental physiology relative to those in humans highlight the need for alternative small animal IUGR models.We developed a guinea pig IUGR model by gradual occlusion of uterine arteries by ameroid constrictor implantation. In this model, reduced uterine blood flow was associated with IUGR, allowing in vivo assessment of fetal growth trajectory and umbilico‐placental vascular function in conscious animals.The intervention induces placental vascular dysfunction and remodelling, as well as altered fetal abdominal growth resulting in an asymmetric IUGR and preserved brain growth. Abstract Intra‐uterine growth restriction (IUGR) is associated with short and long‐term metabolic and cardiovascular alterations. Mice and rats have been extensively used to study the effects of IUGR, but there are notable differences in fetal and placental physiology relative to those of humans that argue for alternative animal models. This study proposes that gradual occlusion of uterine arteries from mid‐gestation in pregnant guinea pigs produces a novel model to better assess human IUGR. Fetal biometry and in vivo placental vascular function were followed by sonography and Doppler of control pregnant guinea pigs and sows submitted to surgical placement of ameroid constrictors in both uterine arteries (IUGR) at mid‐gestation (35 days). The ameroid constrictors induced a reduction in the fetal abdominal circumference growth rate (0.205 cm day−1) compared to control (0.241 cm day−1, P < 0.001) without affecting biparietal diameter growth. Umbilical artery pulsatility and resistance indexes at 10 and 20 days after surgery were significantly higher in IUGR animals than controls (P < 0.01). These effects were associated with a decrease in the relative

  20. Vascular imaging in the elderly.

    PubMed

    Kalva, Sanjeeva P; Mueller, Peter R

    2008-07-01

    Though a myriad of vascular conditions affect the elderly, atherosclerosis remains the most common vascular disorder, followed by venous thromboembolism and varicose veins. In this article, the authors discuss the imaging of atherosclerosis affecting various vascular territories and pay special attention to the elderly population. The authors also discuss imaging findings of segmental arterial mediolysis, giant cell arteritis, and venous thromboembolism.

  1. Functional neuroimaging of human vocalizations and affective speech.

    PubMed

    Frühholz, Sascha; Sander, David; Grandjean, Didier

    2014-12-01

    Neuroimaging studies have verified the important integrative role of the basal ganglia during affective vocalizations. They, however, also point to additional regions supporting vocal monitoring, auditory-motor feedback processing, and online adjustments of vocal motor responses. For the case of affective vocalizations, we suggest partly extending the model to fully consider the link between primate-general and human-specific neural components.

  2. The tyrosine phosphatase SHP-2 controls urokinase-dependent signaling and functions in human vascular smooth muscle cells

    SciTech Connect

    Kiyan, Julia Haller, Hermann; Dumler, Inna

    2009-04-01

    The urokinase (uPA)/urokinase receptor (uPAR) multifunctional system is an important mediator of functional behaviour of human vascular smooth muscle cells (VSMC). uPAR associates with platelet-derived growth factor receptor {beta} (PDGFR-{beta}), which serves as a transmembrane adaptor for uPAR in VSMC, to transduce intracellular signaling and initiate functional changes. The precise and rapid propagation of these signaling cascades demands both strict and flexible regulatory mechanisms that remain unexplored. We provide evidence that the tyrosine phosphatase SHP-2 mediates these processes. uPA regulated SHP-2 phosphorylation, catalytic activity, and its co-localization and association with the PDGFR-{beta}. Active PDGFR-{beta} was required for the uPA-induced SHP-2 phosphorylation. uPAR-directed STAT1 pathway was disturbed in cells expressing SHP-2 inactive mutant. Both, cell proliferation and migration were impaired in VSMC with downregulated SHP-2. Elucidating the underlying mechanisms, we found that uPA induced SHP-2 recruitment to lipid rafts. Disruption of rafts abolished uPA-related control of SHP-2 phosphorylation, its association with PDGFR-{beta} and finally the VSMC functional responses. Our results demonstrate that SHP-2 plays an important role in uPA-directed signaling and functional control of human VSMC and suggest that this phosphatase might contribute to the pathogenesis of the uPA-related vascular remodeling.

  3. Functional and Aesthetic Recovery of Congenital Muscular Torticollis with Intramuscular Stromal Vascular Fraction Enriched Fat Grafting

    PubMed Central

    2017-01-01

    Congenital muscular torticollis is a well-known pathological condition caused by the contracture and shortening of the sternocleidomastoid muscle. This condition is manifested by a neck postural deformity often accompanied by some kind of facial asymmetry. Once diagnosed, treatment by early physiotherapy is generally successful in a high percentage of patients if performed during the first year of life. Later, especially after the fourth year, conservative treatment is usually far less effective, and surgical techniques remain the only way to improve neck contour and function. The author reports two cases of adult patients affected by this condition and successfully treated with a novel therapeutic approach consisting of percutaneous myotomies and intramuscular cell-assisted fat grafting. Two cases of adult patients diagnosed with congenital muscular torticollis were analyzed after treatment with percutaneous myotomies and intramuscular fat grafting. The first patient had a history of unsuccessful treatment in infancy with bipolar release of the sternocleidomastoid muscle and was treated with two sessions of fat grafting. The second patient had a history of neglected torticollis and was treated with a single session of cell-assisted fat grafting. In both cases, facial asymmetries were simultaneously treated with the same fat grafting protocol used to treat the muscle. Improvements in muscle function and in face and neck contours were extremely good and stable in both patients. The postoperative course for both patients was uneventful and with a very short and easy recovery when compared with the techniques described to date. Neglected congenital muscular torticollis in adults, or in patients who have not responded adequately to surgical treatment, has been treated safely with percutaneous myotomies and intramuscular fat grafting. The benefit is a scarless technique that provides simultaneous recovery of neck aesthetics and muscle function together with a very

  4. Functional and Aesthetic Recovery of Congenital Muscular Torticollis with Intramuscular Stromal Vascular Fraction Enriched Fat Grafting.

    PubMed

    Monreal, Juan

    2017-01-12

    Congenital muscular torticollis is a well-known pathological condition caused by the contracture and shortening of the sternocleidomastoid muscle. This condition is manifested by a neck postural deformity often accompanied by some kind of facial asymmetry. Once diagnosed, treatment by early physiotherapy is generally successful in a high percentage of patients if performed during the first year of life. Later, especially after the fourth year, conservative treatment is usually far less effective, and surgical techniques remain the only way to improve neck contour and function. The author reports two cases of adult patients affected by this condition and successfully treated with a novel therapeutic approach consisting of percutaneous myotomies and intramuscular cell-assisted fat grafting. Two cases of adult patients diagnosed with congenital muscular torticollis were analyzed after treatment with percutaneous myotomies and intramuscular fat grafting. The first patient had a history of unsuccessful treatment in infancy with bipolar release of the sternocleidomastoid muscle and was treated with two sessions of fat grafting. The second patient had a history of neglected torticollis and was treated with a single session of cell-assisted fat grafting. In both cases, facial asymmetries were simultaneously treated with the same fat grafting protocol used to treat the muscle. Improvements in muscle function and in face and neck contours were extremely good and stable in both patients. The postoperative course for both patients was uneventful and with a very short and easy recovery when compared with the techniques described to date. Neglected congenital muscular torticollis in adults, or in patients who have not responded adequately to surgical treatment, has been treated safely with percutaneous myotomies and intramuscular fat grafting. The benefit is a scarless technique that provides simultaneous recovery of neck aesthetics and muscle function together with a very

  5. Admixture mapping scans identify a locus affecting retinal vascular caliber in hypertensive African Americans: the Atherosclerosis Risk in Communities (ARIC) study.

    PubMed

    Cheng, Ching-Yu; Reich, David; Wong, Tien Y; Klein, Ronald; Klein, Barbara E K; Patterson, Nick; Tandon, Arti; Li, Man; Boerwinkle, Eric; Sharrett, A Richey; Kao, W H Linda

    2010-04-15

    Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 ancestry-informative SNPs, we estimated the percentage of African ancestry (PAA) and conducted genome-wide admixture mapping scans in 1,737 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) representing summary measures of retinal arteriolar and venular caliber, respectively, were measured from retinal photographs. PAA was significantly correlated with CRVE (rho = 0.071, P = 0.003), but not CRAE (rho = 0.032, P = 0.182). Using admixture mapping, we did not detect significant admixture association with either CRAE (genome-wide score = -0.73) or CRVE (genome-wide score = -0.69). An a priori subgroup analysis among hypertensive individuals detected a genome-wide significant association of CRVE with greater African ancestry at chromosome 6p21.1 (genome-wide score = 2.31, locus-specific LOD = 5.47). Each additional copy of an African ancestral allele at the 6p21.1 peak was associated with an average increase in CRVE of 6.14 microm in the hypertensives, but had no significant effects in the non-hypertensives (P for heterogeneity <0.001). Further mapping in the 6p21.1 region may uncover novel genetic variants affecting retinal vascular caliber and further insights into the interaction between genetic effects of the microvascular system and hypertension.

  6. Prevention and treatment of peritoneal adhesions in patients affected by vascular diseases following surgery: a review of the literature

    PubMed Central

    Aprea, Giovanni; Surfaro, Giuseppe; Amato, Maurizio; Giuliani, Antonio; Paccone, Marianna; Salzano, Andrea; Russo, Anna; Tafuri, Domenico; Amato, Bruno

    2016-01-01

    Abstract Intra-abdominal adhesions are the most frequently occurring postoperative complication following abdomino-pelvic surgery. Abdominal and pelvic surgery can lead to peritoneal adhesion formation causing infertility, chronic pelvic pain, and intestinal obstruction. Laparoscopy today is considered the gold standard of care in the treatment of several abdominal pathologies as well as in a wide range of vascular diseases. Laparoscopy has several advantages in comparison to open surgery. These include rapid recovery times, shorter hospitalisation, reduced postoperative pain, as well as cosmetic benefits. The technological improvements in this particular surgical field along with the development of modern techniques and the acquisition of specific laparoscopic skills have allowed for its wider utilization in operations with fully intracorporeal anastomoses. Postoperative adhesions are caused by aberrant peritoneal healing and are the leading cause of postoperative bowel obstruction. The use of anti-adherence barriers is currently being advocated for their prevention. The outcome of the investigation showed adhesion formation inhibition without direct detrimental effects on anastomotic healing. Poor anasto-motic healing can provoke adhesions even in the presence of anti-adhesion barriers. This review gives a short overview on the current evidence on the pathophysiology and prevention of peritoneal adhesions. PMID:28352777

  7. Administration of thyroxine affects the morphometric parameters and VEGF expression in the uterus and placenta and the uterine vascularization but does not affect reproductive parameters in gilts during early gestation.

    PubMed

    Souza, C A; Ocarino, N M; Silva, J F; Boeloni, J N; Nascimento, E F; Silva, I J; Castro, R D; Moreira, L P; Almeida, F R C L; Chiarini-Garcia, H; Serakides, R

    2011-02-01

    The aim of this study was to evaluate the effects of thyroxine administration on morphometric parameters, expression of vascular endothelial growth factor (VEGF) and vascularization in the uterus and placenta and reproductive parameters in gilts at 70 days of gestation. At 150 days of age, i.e., before first heat, 20 gilts were randomly divided into two experimental groups: treated (n=10) and control (n=10). The treated group received a daily dose of 400 μg of L-thyroxine (T(4)) in their diet until slaughter and the control group received only typical meals. Before artificial insemination, blood was collected to determine plasma total T(4). The gilts were inseminated in the second oestrus and slaughtered at 70 days of gestation. The foetal thyroid follicular epithelium height, number, size and weight of foetuses; foetal myogenesis, corpora lutea number, embryonic mortality rate, uterine weight, placental weight and placental fluid volume were measured. Histomorphometric and immunohistochemical analysis of uterus and placenta were determined. The averages of all variables were compared by the Student's t-test. The gilts treated with thyroxine showed significant increase of plasma total T(4). At 70 days of gestation, the heights of the trophoblastic epithelium, endometrial epithelium and endometrial gland epithelium were significantly higher in the group treated with T(4). The expression of cytoplasmatic and nuclear VEGF in trophoblastic cells and the number of blood vessels per field in endometrial stroma were significantly higher in the gilts treated with T(4). No other significant differences between groups were obtained with respect to other parameters (p>0.05). We conclude that oral administration of T(4) up to 70 days of pregnancy in gilts affects the morphometric parameters, the expression of placental VEGF and the uterine vascularization but does not affect reproductive parameters in gilts during early gestation.

  8. Engineering vascular tissue with functional smooth muscle cells derived from human iPS cells and nanofibrous scaffolds.

    PubMed

    Wang, Yongyu; Hu, Jiang; Jiao, Jiao; Liu, Zhongning; Zhou, Zhou; Zhao, Chao; Chang, Lung-Ji; Chen, Y Eugene; Ma, Peter X; Yang, Bo

    2014-10-01

    Tissue-engineered blood vessels (TEBVs) are promising in the replacement of diseased vascular tissues. However, it remains a great challenge to obtain a sufficient number of functional smooth muscle cells (SMCs) in a clinical setting to construct patient-specific TEBVs. In addition, it is critical to develop a scaffold to accommodate these cells and retain their functional phenotype for the regeneration of TEBVs. In this study, human induced pluripotent stem cells (iPSCs) were established from primary human aortic fibroblasts, and characterized with the pluripotency markers expression and cells' capabilities to differentiate into all three germ layer cells. A highly efficient method was then developed to induce these human iPSCs into proliferative SMCs. After multiple times of expansion, the expanded SMCs retained the potential to be induced into the functional contractile phenotype of mature SMCs, which was characterized by the contractile response to carbachol treatment, up-regulation of specific collagen genes under transforming growth factor β1 treatment, and up-regulation of specific matrix metalloproteinase genes under cytokine stimulation. We also developed an advanced macroporous and nanofibrous (NF) poly(l-lactic acid) (PLLA) scaffold with suitable pore size and interpore connectivity to seed these human iPSC-derived SMCs and maintain their differentiated phenotype. Subcutaneous implantation of the SMC-scaffold construct in nude mice demonstrated vascular tissue formation, with robust collagenous matrix deposition inside the scaffold and the maintenance of differentiated SMC phenotype. Taken together, this study established an exciting approach towards the construction of patient-specific TEBVs. We established patient-specific human iPSCs, derived proliferative SMCs for expansion, turned on their mature contractile SMC phenotype, and developed an advanced scaffold for these cells to regenerate vascular tissue in vivo.

  9. Control of vascular smooth muscle function by Src-family kinases and reactive oxygen species in health and disease.

    PubMed

    MacKay, Charles E; Knock, Greg A

    2015-09-01

    Reactive oxygen species (ROS) are now recognised as second messenger molecules that regulate cellular function by reversibly oxidising specific amino acid residues of key target proteins. Amongst these are the Src-family kinases (SrcFKs), a multi-functional group of non-receptor tyrosine kinases highly expressed in vascular smooth muscle (VSM). In this review we examine the evidence supporting a role for ROS-induced SrcFK activity in normal VSM contractile function and in vascular remodelling in cardiovascular disease. VSM contractile responses to G-protein-coupled receptor stimulation, as well as hypoxia in pulmonary artery, are shown to be dependent on both ROS and SrcFK activity. Specific phosphorylation targets are identified amongst those that alter intracellular Ca(2+) concentration, including transient receptor potential channels, voltage-gated Ca(2+) channels and various types of K(+) channels, as well as amongst those that regulate actin cytoskeleton dynamics and myosin phosphatase activity, including focal adhesion kinase, protein tyrosine kinase-2, Janus kinase, other focal adhesion-associated proteins, and Rho guanine nucleotide exchange factors. We also examine a growing weight of evidence in favour of a key role for SrcFKs in multiple pro-proliferative and anti-apoptotic signalling pathways relating to oxidative stress and vascular remodelling, with a particular focus on pulmonary hypertension, including growth-factor receptor transactivation and downstream signalling, hypoxia-inducible factors, positive feedback between SrcFK and STAT3 signalling and positive feedback between SrcFK and NADPH oxidase dependent ROS production. We also discuss evidence for and against the potential therapeutic targeting of SrcFKs in the treatment of pulmonary hypertension.

  10. Homocysteine and nitric oxide are related to blood pressure and vascular function in small-for-gestational-age children.

    PubMed

    Franco, Maria C P; Higa, Elisa M S; D'Almeida, Vânia; de Sousa, Fernanda G; Sawaya, Ana L; Fortes, Zuleica B; Sesso, Ricardo

    2007-08-01

    Leptin, homocysteine (Hcy), and C-reactive protein are risk factors potentially useful in predicting future cardiac events. These plasma biomarkers may participate in the regulation of cardiovascular function through an NO-dependent mechanism. Our purpose was to investigate whether alterations in C-reactive protein, Hcy, leptin, and NO are present in small-for-gestational-age children and to determine whether the levels of these plasma biomarkers are associated with birth weight, vascular function, and blood pressure. Concentrations of leptin, Hcy, C-reactive protein, and NO were measured in 69 children (36 boys and 33 girls; ages 8 to 13 years). Leptin (means difference: 1.4 ng/mL; 95% CI: 0.4 to 2.4) and Hcy (means difference: 0.9 micromol/L; 95% CI: 0.3 to 1.5) levels were significantly elevated in children born small for gestational age compared with those with appropriate birth weight. Nevertheless, NO (means difference: 342.9 micromol; 95% CI: 124.2 to 561.6) concentration was significantly reduced in small birth weight children, and the levels of C-reactive protein remained unchanged. There was a significant association between the circulating levels of both NO and Hcy with vascular function, as well as with blood pressure levels, in our population. Because both Hcy and NO are associated with a risk of cardiovascular disease, it is possible that part of the association of low birth weight with elevated risk for vascular and metabolic disease in later life is mediated by perturbation in pathways for these biomarkers.

  11. The relationship between ventricular-vascular uncoupling during exercise and impaired left ventricular longitudinal functional reserve in hypertensive patients.

    PubMed

    Shim, Chi Young; Park, Sungha; Choi, Eui-Young; Hong, Geu-Ru; Choi, Donghoon; Jang, Yangsoo; Chung, Namsik

    2013-01-01

    Uncoupling between heart and vessel may be accompanied by left ventricular (LV) dysfunction during exercise. We investigated the association between ventricular-vascular uncoupling during exercise and impaired LV longitudinal functional reserve in hypertensive subjects. Supine bicycle exercise echocardiography (25-watt, 3-minute increments) was performed in 216 hypertensive patients (106 male; mean age, 58 ± 9 years). Arterial elastance (Ea), end-systolic ventricular elastance (Ees), and ventricular-vascular interaction (VVI) index (Ea/Ees) were calculated at rest and at each stage of exercise. The patients were divided into three groups according to the tertile value of VVI ratio. The VVI ratio was defined as the ratio of VVI index at 50 W exercise over VVI index at rest; normal VVI response (n = 72); borderline VVI response (n = 72); and abnormal VVI response (n = 72). There were no significant differences in conventional echo parameters, mitral inflow velocities, mitral annular early diastolic (E') velocity, and mitral annular systolic velocity (S') at rest among the three groups. However, E' velocities and S' velocities at 25 W and 50 W were significantly lower in patients with abnormal VVI response compared with those in the other groups (P = .010 at 25 W, P = .008 at 50 W in E' velocity; P = .022 at 25 W, P = .043 at 50 W in S' velocity). Longitudinal diastolic functional reserve index from rest to 50 W was significantly lower in patients with abnormal VVI response compared with the other groups. Ventricular-vascular uncoupling during exercise was related to impaired LV longitudinal functional reserve in hypertensive patients.

  12. The effects of a lupin-enriched diet on oxidative stress and factors influencing vascular function in overweight subjects.

    PubMed

    Yang, Xingbin; Croft, Kevin D; Lee, Ya P; Mori, Trevor A; Puddey, Ian B; Sipsas, Sofia; Barden, Anne; Swinny, Ewald; Hodgson, Jonathan M

    2010-11-15

    A diet enriched in lupin kernel flour can lower blood pressure, but mechanisms responsible are unclear. Lupin is a source of polyphenols, protein, and L-arginine, factors that may influence blood pressure via effects on oxidative stress and vascular function. Therefore, we aimed to determine the effects of a lupin-enriched diet on oxidative stress and factors influencing vascular function as potential mechanisms for demonstrated benefits on blood pressure. Overweight men and women (n = 88) were recruited to a 16-week parallel-design study. Participants were randomly assigned to replace 15%-20% of their usual daily energy intake with white bread (control) or lupin kernel flour-enriched bread (lupin). All measurements were taken at baseline and 16 weeks. At baseline, plasma F₂-isoprostanes and 20-hydroxyeicosatetraenoic acid (20-HETE) were positively associated with blood pressure, and plasma nitrite was negatively associated with blood pressure (p < 0.05). For lupin relative to control, the estimated differences in plasma F₂-isoprostanes (45 pmol/L; 95%CI: -68, 158), urinary F₂-isoprostanes (17 pmol/mmol creatinine; 95%CI: -43, 76), plasma 20-HETE (75 pmol/L; 95%CI: -91, 241), and plasma nitrite (-0.3 μmol/L; 95%CI: -1.1, 0.4) were not significant. Although regular consumption of lupin-enriched bread can lower blood pressure, these results do not support for the hypothesis that this is via effects on oxidative stress or vascular function.

  13. Frozen Soil Characteristics That Affect Land Mine Functioning.

    DTIC Science & Technology

    1983-04-01

    ii Introduction .............................................. 1 Backgroun ...Table 3 also presents the results of the mine functioning perform- ance . The M12 mine requires between 1739 and 3287 N to function, as indicated by the

  14. Functional vascular renin-angiotensin system in hypertensive transgenic rats for the mouse renin gene Ren-2.

    PubMed

    Arribas, S; Sánchez-Ferrer, C F; Peiró, C; Ponte, A; Salaices, M; Marín, J

    1994-10-01

    1. Isolated aortic segments from transgenic rats for the mouse renin gene Ren-2 were more sensitive than those from control Sprague-Dawley ones to the vasoconstrictions induced by angiotensin II and to the potentiation of norepinephrine contractions by this peptide. 2. In transgenic, but not in control aorta, pretreatment with angiotensinogen potentiated norepinephrine-induced vasoconstrictions, this effect being abolished by captopril. 3. These results suggest that in the aorta of transgenic rats there is a higher functional tissue renin-angiotensin system that potentiates the vascular reactivity to norepinephrine.

  15. Does the type and size of Amplatzer vascular plug affect the occlusion time of pulmonary arteriovenous malformations?

    PubMed Central

    Abdel-Aal, Ahmed Kamel; Massoud, Moustafa Omar; Elantably, Dina Mahmoud

    2017-01-01

    PURPOSE Occlusion time (OT) is an important factor in the treatment of pulmonary arteriovenous malformations (PAVMs) since it can lead to serious complications. The purpose of our study is to calculate the OT of Amplatzer vascular plug (AVP, St Jude Medical), and correlate it to the type of the device used (AVP or AVP 2) and the percent of device oversizing. Technical success rates and complications were also recorded. METHODS We retrospectively studied a total of 19 patients with 47 PAVMs who received percutaneous transcatheter embolization therapy using either AVP or AVP 2. We recorded the location, type, feeding artery diameter, AVP device used, and OT of each PAVM. We correlated the percent of device oversizing and the type of AVP with the OT. We also studied the rate of persistence of PAVM for both devices. RESULTS Forty-six (98%) of the PAVMs were simple. Device diameters ranged from 4.0–16.0 mm with device oversizing ranging between 14% and 120%. There was a statistically significant difference in the OT of AVP and AVP 2 (3 min 54 s vs. 5 min 30 s, P = 0.030). There was a weak positive correlation between OT and device oversizing for AVP (r=0.246, P = 0.324) and AVP 2 (r=0.261, P = 0.240). No major complications were identified. Immediate technical success rate was 100%. CONCLUSION The use of AVP 2, and increase in device oversizing were not associated with reduction in the OT of PAVMs. There was no reported difference in safety between the two devices, and no major complications were noted. PMID:27856403

  16. Bromovirus movement protein conditions for the host specificity of virus movement through the vascular system and affects pathogenicity in cowpea.

    PubMed

    Fujita, Y; Fujita, M; Mise, K; Kobori, T; Osaki, T; Furusawa, I

    2000-11-01

    Previously, we reported that CCMV(B3a), a hybrid of bromovirus Cowpea chlorotic mottle virus (CCMV) with the 3a cell-to-cell movement protein (MP) gene replaced by that of cowpea-nonadapted bromovirus Brome mosaic virus (BMV), can form small infection foci in inoculated cowpea leaves, but that expansion of the foci stops between 1 and 2 days postinoculation. To determine whether the lack of systemic movement of CCMV(B3a) is due to restriction of local spread at specific leaf tissue interfaces, we conducted more detailed analyses of infection in inoculated leaves. Tissue-printing and leaf press-blotting analyses revealed that CCMV(B3a) was confined to the inoculated cowpea leaves and exhibited constrained movement into leaf veins. Immunocytochemical analyses to examine the infected cell types in inoculated leaves indicated that CCMV(B3a) was able to reach the bundle sheath cells through the mesophyll cells and successfully infected the phloem cells of 50% of the examined veins. Thus, these data demonstrate that the lack of long-distance movement of CCMV(B3a) is not due to an inability to reach the vasculature, but results from failure of the virus to move through the vascular system of cowpea plants. Further, a previously identified 3a coding change (A776C), which is required for CCMV(B3a) systemic infection of cowpea plants, suppressed formation of reddish spots, mediated faster spread of infection, and enabled the virus to move into the veins of inoculated cowpea leaves. From these data, and the fact that CCMV(B3a) directs systemic infection in Nicotiana benthamiana, a permissive systemic host for both BMV and CCMV, we conclude that the bromovirus 3a MP engages in multiple activities that contribute substantially to host-specific long-distance movement through the phloem.

  17. Changes in vascular and transpiration flows affect the seasonal and daily growth of kiwifruit (Actinidia deliciosa) berry

    PubMed Central

    Morandi, Brunella; Manfrini, Luigi; Losciale, Pasquale; Zibordi, Marco; Corelli Grappadelli, Luca

    2010-01-01

    Background and Aims The kiwifruit berry is characterized by an early stage of rapid growth, followed by a relatively long stage of slow increase in size. Vascular and transpiration flows are the main processes through which water and carbon enter/exit the fruit, determining the daily and seasonal changes in fruit size. This work investigates the biophysical mechanisms underpinning the change in fruit growth rate during the season. Methods The daily patterns of phloem, xylem and transpiration in/outflows have been determined at several stages of kiwifruit development, during two seasons. The different flows were quantified by comparing the diurnal patterns of diameter change of fruit, which were then girdled and subsequently detached while measurements continued. The diurnal courses of leaf and stem water potential and of fruit pressure potential were also monitored at different times during the season. Key Results Xylem and transpiration flows were high during the first period of rapid volume growth and sharply decreased with fruit development. Specific phloem import was lower and gradually decreased during the season, whereas it remained constant at whole-fruit level, in accordance with fruit dry matter gain. On a daily basis, transpiration always responded to vapour pressure deficit and contributed to the daily reduction of fruit hydrostatic pressure. Xylem flow was positively related to stem-to-fruit pressure potential gradient during the first but not the last part of the season, when xylem conductivity appeared to be reduced. Conclusions The fruit growth model adopted by this species changes during the season due to anatomical modifications in the fruit features. PMID:20382641

  18. Hyperthermia Severely Affects the Vascular Effects of MDMA and Metabolites in the Human Internal Mammary Artery In Vitro.

    PubMed

    Fonseca, D A; Guerra, A F; Carvalho, F; Fernandes, E; Ferreira, L M; Branco, P S; Antunes, P E; Antunes, M J; Cotrim, M D

    2017-01-13

    3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a recreational drug used worldwide for its distinctive psychotropic effects. Although important cardiovascular effects, such as increased blood pressure and heart rate, have also been described, the vascular effects of MDMA and metabolites and their correlation with hyperthermia (major side effect of MDMA) are not yet fully understood and have not been previously reported. This study aimed at evaluating the effects of MDMA and its main catechol metabolites, alpha-methyldopamine (α-MeDA), N-methyl-alpha-methyldopamine (N-Me-α-MeDA), 5-(glutathion-S-yl)-alpha-methyldopamine [5-(GSH)-α-MeDA] and 5-(glutathion-S-yl)-N-methyl-alpha-methyldopamine [5-(GSH)-N-Me-α-MeDA], on the 5-HT-dependent vasoactivity in normothermia (37 °C) and hyperthermia (40 °C) of the human internal mammary artery (IMA) in vitro. The results showed the ability of MDMA, α-MeDA and N-Me-α-MeDA to exert vasoconstriction of the IMA which was considerably higher in hyperthermic conditions (about fourfold for MDMA and α-MeDA and twofold for N-Me-α-MeDA). The results also showed that all the compounds may influence the 5-HT-mediated concentration-dependent response of IMA, as MDMA, α-MeDA and N-Me-α-MeDA behaved as partial agonists and 5-(GSH)-α-MeDA and 5-(GSH)-N-Me-α-MeDA as antagonists. In conclusion, MDMA abuse may imply a higher cardiovascular risk associated both to MDMA and its metabolites that might be relevant in patients with underlying cardiovascular diseases, particularly in hyperthermia.

  19. Effect of computerized cognitive training with virtual spatial navigation task during bed rest immobilization and recovery on vascular function: A pilot study

    PubMed Central

    Goswami, Nandu; Kavcic, Voyko; Marusic, Uros; Simunic, Bostjan; Rössler, Andreas; Hinghofer-Szalkay, Helmut; Pisot, Rado

    2015-01-01

    We investigated the effects of bed rest (BR) immobilization, with and without computerized cognitive training with virtual spatial navigation task (CCT), on vascular endothelium on older subjects. The effects of 14-day BR immobilization in healthy older males (n=16) of ages 53–65 years on endothelial function were studied using EndoPAT®, a noninvasive and user-independent method. From the group of 16 older men, 8 randomly received CCT during the BR, using virtual navigation tasks in a virtual environment with joystick device. In all the cases, EndoPAT assessments were done at pre- and post-BR immobilization as well as following 28 days of ambulatory recovery. The EndoPAT index increased from 1.53±0.09 (mean ± standard error of the mean) at baseline to 1.61±0.16 following immobilization (P=0.62) in the group with CCT. The EndoPAT index decreased from 2.06±0.13 (mean ± standard error of the mean) at baseline to 1.70±0.09 at the last day of BR study, day 14 (BR14) (P=0.09) in the control group. Additionally, there were no statistically significant differences between BR14 and at 28 days of follow-up (rehabilitation program) (R28). Our results show a trend of immobilization in older persons affecting the vasoconstrictory endothelial response. As the control subjects had a greater increase in EndoPAT index after R28 (+0.018) compared to subjects who had cognitive training (+0.11) (calculated from the first day of BR study), it is possible that cognitive training during BR does not improve endothelial function but rather contributes to slowing down the impairment of endothelial function. Finally, our results also show that EndoPAT may be a useful noninvasive tool to assess the vascular reactivity. PMID:25709419

  20. Effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in people with arterial vascular disease with and without COPD

    PubMed Central

    Key, Angela; Parry, Matthew; West, Malcolm A; Asher, Rebecca; Jack, Sandy; Duffy, Nick; Torella, Francesco

    2017-01-01

    Introduction β Blockers are important treatment for ischaemic heart disease and heart failure; however, there has long been concern about their use in people with chronic obstructive pulmonary disease (COPD) due to fear of symptomatic worsening of breathlessness. Despite growing evidence of safety and efficacy, they remain underused. We examined the effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in a group of vascular surgical patients, a high proportion of who were expected to have COPD. Methods People undergoing routine abdominal aortic aneurysm (AAA) surveillance were sequentially recruited from vascular surgery clinic. They completed plethysmographically measured lung function and incremental cardiopulmonary exercise testing with dynamic measurement of inspiratory capacity while taking and not taking β blocker. Results 48 participants completed tests while taking and not taking β blockers with 38 completing all assessments successfully. 15 participants (39%) were found to have, predominantly mild and undiagnosed, COPD. People with COPD had airflow obstruction, increased airway resistance (Raw) and specific conductance (sGaw), static hyperinflation and dynamically hyperinflated during exercise. In the whole group, β-blockade led to a small fall in FEV1 (0.1 L/2.8% predicted) but did not affect Raw, sGaw, static or dynamic hyperinflation. No difference in response to β-blockade was seen in those with and without COPD. Conclusions In people with AAA, β-blockade has little effect on lung function and dynamic hyperinflation in those with and without COPD. In this population, the prevalence of COPD is high and consideration should be given to case finding with spirometry. Trial registration number NCT02106286.

  1. Penile vascular evaluation and sexual function before and after radical retropubic prostatectomy: 5-year follow-up.

    PubMed

    Dubbelman, Yvette D; Wildhagen, Mark F; Dohle, Gert R

    2008-09-01

    Sexual dysfunction is common after surgery for prostate cancer. The aetiology of changes in sexual potency after radical prostatectomy is probably multifactorial, including neurogenic, vascular and psychosexual factors. A prospective study was designed to investigate haemodynamic and psychosexual changes before and after radical retropubic prostatectomy (RRP) for organ-confined prostate cancer. Penile haemodynamic evaluation and an assessment of sexual excitement were performed preoperatively and 3 months after RRP by colour Doppler ultrasonography (CDU) with visual erotic stimulation combined with a single intracavernous injection of a mixture of papaverine/phentolamine. Questionnaires on sexual function [International Index of Erectile Function (IIEF)], general health and quality of life were sent to the patients preoperative, 3 months and 5 years after operation. Forty-eight men participated in the study. Mean age was 62.6 years (range 55-69). CDU did not show any significant reduction in mean peak systolic flow velocity and mean resistance index. From the men who preoperatively had normal arterial inflow 18% developed arteriogenic insufficiency. Some form of veno-occlusive insufficiency and low resistance indices were already present in the majority of normal potent men preoperatively. Surgical technique did not influence penile arterial blood flow after the operation. Three months and 5 years postoperatively, there was a highly significant reduction in erectile function, intercourse satisfaction, overall satisfaction, orgasmic function and sexual desire. However, with respect to the outcome at 3 months there was a significant improvement of orgasmic function 5 years after operation, especially after a bilateral nerve sparing procedure. Erections sufficient for vaginal penetration (questions 3 and 4 of the IIEF, score >or=8) improved from 2% to 11% 3 months and 5 years after RRP respectively. Total IIEF score was significantly better after a bilateral nerve

  2. The dual PPARα/γ agonist aleglitazar increases the number and function of endothelial progenitor cells: implications for vascular function and atherogenesis

    PubMed Central

    Werner, C M; Schirmer, S H; Gensch, C; Pavlickova, V; Pöss, J; Wright, M B; Böhm, M; Laufs, U

    2014-01-01

    Background and Purpose Aleglitazar is a dual PPARα/γ agonist but little is known about its effects on vascular function and atherogenesis. Hence, we characterized its effects on circulating angiogenic cells (CAC), neoangiogenesis, endothelial function, arteriogenesis and atherosclerosis in mice. Experimental Approach C57Bl/6 wild-type (WT, normal chow), endothelial NOS (eNOS)−/− (normal chow) and ApoE−/− (Western-type diet) mice were treated with aleglitazar (10 mg·kg−1·day−1, i.p.) or vehicle. Key Results Aleglitazar enhanced expression of PPARα and PPARγ target genes, normalized glucose tolerance and potently reduced hepatic fat in ApoE−/− mice. In WT mice, but not in eNOS−/−, aleglitazar up-regulated Sca-1/VEGFR2-positive CAC in the blood and bone marrow and up-regulated diLDL/lectin-positive CAC. Aleglitazar augmented CAC migration and enhanced neoangiogenesis. In ApoE−/− mice, aleglitazar up-regulated CAC number and function, reduced markers of vascular inflammation and potently improved perfusion restoration after hindlimb ischaemia and aortic endothelium-dependent vasodilatation. This was associated with markedly reduced formation of atherosclerotic plaques. In human cultured CAC from healthy donors and patients with coronary artery disease with or without diabetes mellitus, aleglitazar increased migration and colony-forming units in a concentration-dependent manner. Furthermore, oxidative stress-induced CAC apoptosis and expression of p53 were reduced, while telomerase activity and expression of phospho-eNOS and phospho-Akt were elevated. Comparative agonist and inhibitor experiments revealed that aleglitazar's effects on CAC migration and colony-forming units were mediated by both PPARα and PPARγ signalling and required Akt. Conclusions and Implications Aleglitazar augments the number, function and survival of CAC, which correlates with improved vascular function, enhanced arteriogenesis and prevention of atherosclerosis

  3. Concomitant gastroparesis negatively affects children with functional gallbladder disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the present study was to determine whether concomitant gastroparesis and biliary dyskinesia (BD) occur in children, and if so, to determine whether concomitant gastroparesis affects clinical outcome in children with BD. We conducted a retrospective chart review of children with BD (ejecti...

  4. Spectral imaging of microvascular function in a renal cell carcinoma after treatment with a vascular disrupting agent

    NASA Astrophysics Data System (ADS)

    Wankhede, Mamta; deDeugd, Casey; Siemann, Dietmar W.; Sorg, Brian S.

    2009-02-01

    Tumors are highly metabolically active and thus require ample oxygen and nutrients to proliferate. Neovasculature generated by angiogenesis is required for tumors to grow beyond a size of about 1-2mm. Functional tumor vasculature also provides an access point for development of distant metastases. Due to the importance of the microvasculature for tumor growth, proliferation, and metastasis, the microvasculature has emerged as a therapeutic target for treatment of solid tumors. We employed spectral imaging in a rodent window chamber model to observe and measure the oxygen transport function of tumor microvasculature in a human renal cell carcinoma after treatment with a fast acting vascular disrupting agent. Human Caki-1 cells were grown in a dorsal skin-fold window chamber in athymic nude mice. Spectral imaging was used to measure hemoglobin saturation immediately before, immediately after and also at 2, 4, 6, 8, 24 and 48 hours after administration of the tubulin binding agent OXi4503. Up to 4 hours after treatment, tumor microvasculature was disrupted from the tumor core towards the periphery as seen in deoxygenation as well as structural changes of the vasculature. Reoxygenation and neovascularization commenced from the periphery towards the core from 6 - 48 hours after treatment. The timing of the effects of vascular disrupting agents can influence scheduling of repeat treatments and combinatorial treatments such as chemotherapy and radiation therapy. Spectral imaging can potentially provide this information in certain laboratory models from endogenous signals with microvessel resolution.

  5. Circulating vascular endothelial growth factor and its soluble receptors in patients with liver cirrhosis: possible association with hepatic function impairment.

    PubMed

    Jaroszewicz, Jerzy; Januszkiewicz, Marcin; Flisiak, Robert; Rogalska, Magdalena; Kalinowska, Alicja; Wierzbicka, Iwona

    2008-10-01

    Recent studies provided in vivo evidences of an increased angiogenesis in animal model of portal hypertension and cirrhosis which was linked to increased expression of vascular endothelial growth factor. The aim of study was to evaluate the plasma concentration of VEGF and its receptors in liver cirrhosis and the possible association with the degree of liver insufficiency. Methods. Vascular endothelial growth factor (VEGF) and its soluble receptors: sVEGF-R1, sVEGF-R2 were measured in plasma of 78 patients with liver cirrhosis by ELISA. Results. The significant increase of plasma VEGF and sVEGF-R1 was observed in liver cirrhosis compared to healthy individuals (153.1+/-51.9 vs. 46.8+/-4.1pg/mL, P<0.05; 279.8+/-34.3 vs. 105.1+/-5.9pg/mL, P<0.001, respectively). Plasma VEGF and foremost sVEGF R1 showed significant associations with biochemical indices of liver function. Among clinical parameters, only ascites revealed significant association with plasma VEGR and sVEGF-R1. VEGF and sVEGF-R1 were increased respectively to the degree of liver insufficiency. It was demonstrated through a significant positive correlation with Child-Pugh score and MELD classification. In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms.

  6. Association between smoking status and the parameters of vascular structure and function in adults: results from the EVIDENT study

    PubMed Central

    2013-01-01

    Background The present study analyses the relation between smoking status and the parameters used to assess vascular structure and function. Methods This cross-sectional, multi-centre study involved a random sample of 1553 participants from the EVIDENT study. Measurements: The smoking status, peripheral augmentation index and ankle-brachial index were measured in all participants. In a small subset of the main population (265 participants), the carotid intima-media thickness and pulse wave velocity were also measured. Results After controlling for the effect of age, sex and other risk factors, present smokers have higher values of carotid intima-media thickness (p = 0.011). Along the same lines, current smokers have higher values of pulse wave velocity and lower mean values of ankle-brachial index but without statistical significance in both cases. Conclusions Among the parameters of vascular structure and function analysed, only the IMT shows association with the smoking status, after adjusting for confounders. PMID:24289208

  7. Breast cancer drugs dampen vascular functions by interfering with nitric oxide signaling in endothelium

    SciTech Connect

    Gajalakshmi, Palanivel; Priya, Mani Krishna; Pradeep, Thangaraj; Behera, Jyotirmaya; Muthumani, Kandasamy; Madhuwanti, Srinivasan; Saran, Uttara; Chatterjee, Suvro

    2013-06-01

    Widely used chemotherapeutic breast cancer drugs such as Tamoxifen citrate (TC), Capecitabine (CP) and Epirubicin (EP) are known to cause various cardiovascular side-effects among long term cancer survivors. Vascular modulation warrants nitric oxide (NO) signal transduction, which targets the vascular endothelium. We hypothesize that TC, CP and EP interference with the nitric oxide downstream signaling specifically, could lead to cardiovascular dysfunctions. The results demonstrate that while all three drugs attenuate NO and cyclic guanosine mono-phosphate (cGMP) production in endothelial cells, they caused elevated levels of NO in the plasma and RBC. However, PBMC and platelets did not show any significant changes under treatment. This implies that the drug effects are specific to the endothelium. Altered eNOS and phosphorylated eNOS (Ser-1177) localization patterns in endothelial cells were observed following drug treatments. Similarly, the expression of phosphorylated eNOS (Ser-1177) protein was decreased under the treatment of drugs. Altered actin polymerization was also observed following drug treatment, while addition of SpNO and 8Br-cGMP reversed this effect. Incubation with the drugs decreased endothelial cell migration whereas addition of YC-1, SC and 8Br-cGMP recovered the effect. Additionally molecular docking studies showed that all three drugs exhibited a strong binding affinity with the catalytic domain of human sGC. In conclusion, results indicate that TC, CP and EP cause endothelial dysfunctions via the NO–sGC–cGMP pathway and these effects could be recovered using pharmaceutical agonists of NO signaling pathway. Further, the study proposes a combination therapy of chemotherapeutic drugs and cGMP analogs, which would confer protection against chemotherapy mediated vascular dysfunctions in cancer patients. - Highlights: • NO production is reduced in endothelial cells under breast cancer drug treatment. • Cellular cGMP level is decreased under

  8. Atherosclerosis in Psoriatic Arthritis: A Multiparametric Analysis Using Imaging Technique and Laboratory Markers of Inflammation and Vascular Function.

    PubMed

    Garg, Nidhi; Krishan, Pawan; Syngle, Ashit

    2016-12-01

    Cardiovascular disease is one of the leading causes of death in psoriatic arthritis (PsA). Pathogenesis of accelerated atherosclerosis in PsA remains to be elucidated. Endothelial dysfunction (ED) often precedes manifesting atherosclerosis. This study aims to assess carotid intima-media thickness (CIMT), a marker of atherosclerosis in PsA, in context of markers of inflammation and vascular function. A cross-sectional study was performed in 18 PsA patients who were compared with 18 controls matched for age and sex. Flow-mediated dilatation (FMD) assessed by AngioDefender (Everist Health, Ann Arbor, MI), endothelial progenitor cells (EPCs) quantified by flow cytometry and CIMT measured ultrasonographically. Inflammatory measures included disease activity score of 28 joints count and disease activity index in psoriatic arthritis. We also assayed markers of inflammation, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), proinflammatory cytokines (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-α), and endothelial dysfunction, including lipids, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and EPCs. CIMT is significantly higher in PsA patients compared with controls (0.062 ± 0.18 vs. 0.045 ± 0.10 cm, p < 0.01) whereas FMD%, EPCs%, and high-density lipoproteins (HDL) cholesterol are significantly reduced in PsA compared with controls (p < 0.05). Compared with controls, PsA patients had significantly increased concentrations of ESR, CRP, TNF-α, IL-6, ICAM-1, and VCAM-1. In PsA, CIMT positively correlated with IL-6 and ICAM-1 and inversely correlated with FMD, HDL, and EPCs (p < 0.05). In PsA, FMD and CIMT were impaired, indicating endothelial dysfunction and accelerated atherosclerosis, respectively. PsA-related inflammatory mechanisms (TNF-α, IL-6) and markers of vascular function (CRP, ICAM-1, and EPCs) may all be involved in the development of vascular disease in Ps

  9. Palmitic acid increases pro-oxidant adaptor protein p66Shc expression and affects vascularization factors in angiogenic mononuclear cells: Action of resveratrol.

    PubMed

    Favre, Julie; Yildirim, Cansu; Leyen, Thomas A; Chen, Weena J Y; van Genugten, Renate E; van Golen, Larissa W; Garcia-Vallejo, Juan-Jesus; Musters, Rene; Baggen, Josefien; Fontijn, Ruud; van der Pouw Kraan, Tineke; Serné, Erik; Koolwijk, Pieter; Diamant, Michaela; Horrevoets, Anton J G

    2015-12-01

    A defect in neo-vascularization process involving circulating angiogenic mononuclear cells (CACs) dysfunction is associated with diabetes. We showed that oxidative stress was elevated in CACs cultured from blood of individuals with metabolic syndrome (MetS) and diabetes. We then assessed the action of palmitic acid (PA), a deregulated and increased NEFA in metabolic disorders, focusing on its oxidant potential. We observed that the phyto-polyphenol resveratrol normalized oxidative stress both in CACs isolated from MetS patients or treated with PA. Resveratrol further decreased the deleterious action of PA on gene expression of vascularization factors (TNFα, VEGF-A, SDF1α, PECAM-1, VEGFR2, Tie2 and CXCR4) and improved CAC motility. Particularly, resveratrol abolished the PA-induced over-expression of the pro-oxidant protein p66Shc. Neither KLF2 nor SIRT1, previously shown in resveratrol and p66Shc action, was directly involved. Silencing p66Shc normalized PA action on VEGF-A and TNFα specifically, without abolishing the PA-induced oxidative stress, which suggests a deleterious role of p66Shc independently of any major modulation of the cellular oxidative status in a high NEFA levels context. Besides showing that resveratrol reverses PA-induced harmful effects on human CAC function, certainly through profound cellular modifications, we establish p66Shc as a major therapeutic target in metabolic disorders, independent from glycemic control.

  10. Porphyromonas gingivalis infection modifies oral microcirculation and aortic vascular function in the stroke-prone spontaneously hypertensive rat (SHRSP).

    PubMed

    Funaki, Seiko; Tokutomi, Fumiaki; Wada-Takahashi, Satoko; Yoshino, Fumihiko; Yoshida, Ayaka; Maehata, Yojiro; Miyamoto, Chihiro; Toyama, Toshizo; Sato, Takenori; Hamada, Nobushiro; Lee, Masaichi Chang-il; Takahashi, Shun-suke

    2016-03-01

    The functional modulation of vascular endothelial cells associated with stroke and periodontal disease has not yet been clarified. The objective of this study is to analyze the vascular endothelial function of periodontitis and stroke animal models. We examined endothelial function and gingival blood flow in oral microcirculation in vivo and measured the isometric tension in vitro of the aorta in animal models for lifestyle-related diseases, such as periodontitis and stroke. Gingival reactive hyperemia (GRH) was measured using laser Doppler flowmetry. Wistar Kyoto rats (WKY) were used as control animals; Porphyromonas gingivalis (P. gingivalis) infected WKY (WKY + Pg) as the periodontitis model; stroke-prone spontaneously hypertensive rat (SHRSP) as the stroke model; and a final group consisting of P. gingivalis infected SHRSP (SHRSP + Pg). Furthermore, for each group, the relaxation of descending aortic ring preparations was measured using a force transducer. The GRH was estimated by maximum response (peak), time taken for the maximum response to fall to one half (T1/2), and increased total amount of blood flow (mass). The relative change in T1/2 and mass increased in SHRSP + Pg compared to WKY. However, mass significantly increased in WKY (758.59 ± 88.21 ml/min/100 g s to 1755.55 ± 226.10 ml/min/100 g s) and SHRSP (1214.87 ± 141.61 ml/min/100 g s to 2674.32 ± 675.48 ml/min/100 g s) after treatment with acetylcholine. In addition, T1/2 and mass significantly increased in WKY + Pg (624.18 ± 96.36 ml/min/100 g s to 2629.90 ± 612.01 ml/min/100 g s) and SHRSP + Pg (1116.36 ± 206.24 ml/min/100 g s to 1952.76 ± 217.39 ml/min/100 g s) after treatment with nitroglycerin. Furthermore, the endothelium-dependent relaxation of ring preparations, evoked by acetylcholine, was attenuated in SHRSP compared with WKY, but not in SHRSP + Pg. This attenuation effect in SHRSP could be prevented by superoxide dismutase pretreatment. Our results suggest altered endothelial

  11. Gene expression profiling during intensive cardiovascular lifestyle modification: Relationships with vascular function and weight loss

    PubMed Central

    Blackburn, Heather L.; McErlean, Seóna; Jellema, Gera L.; van Laar, Ryan; Vernalis, Marina N.; Ellsworth, Darrell L.

    2015-01-01

    Heart disease and related sequelae are a leading cause of death and healthcare expenditure throughout the world. Although many patients opt for surgical interventions, lifestyle modification programs focusing on nutrition and exercise have shown substantial health benefits and are becoming increasing popular. We conducted a year-long lifestyle modification program to mediate cardiovascular risk through traditional risk factors and to investigate how molecular changes, if present, may contribute to long-term risk reduction. Here we describe the lifestyle intervention, including clinical and molecular data collected, and provide details of the experimental methods and quality control parameters for the gene expression data generated from participants and non-intervention controls. Our findings suggest successful and sustained modulation of gene expression through healthy lifestyle changes may have beneficial effects on vascular health that cannot be discerned from traditional risk factor profiles. The data are deposited in the Gene Expression Omnibus, series GSE46097 and GSE66175. PMID:26484175

  12. Cardiac autonomic function and vascular profile in subclinical hypothyroidism: Increased beat-to-beat QT variability

    PubMed Central

    Kalra, Pramila; Yeragani, Vikram K.; Prasanna Kumar, K. M.

    2016-01-01

    Background: Patients with subclinical hypothyroidism (SH) may have higher incidence of coronary heart disease and autonomic dysfunction. Design of the Study: Prospective case control study. Aim and Objectives: To evaluate beat-to-beat QT variability and vascular stiffness in patients with SH compared to normal controls. Materials and Methods: We compared linear and nonlinear measures of cardiac repolarization liability using beat-to-beat QT intervals derived from the surface electrocardiogram during supine posture and vascular indices including pulse wave velocity and ankle-brachial index (ABI) during supine posture between female patients with SH and age- and sex-matched normal controls. Spectral analysis was done at very low frequency (LF) (0.003–0.04 Hz), Low frequency (LF) (0.04–0.15 Hz), and high frequency (HF) (0.15–0.4 Hz). The HF represents vagal regulation (parasympathetic) and LF represents both parasympathetic and sympathetic regulation. Results: We recruited 58 women with a mean age of 31.83 ± 8.9 years and 49 controls with mean age of 32.4 ± 9.9 years (P = NS). QT variability index (QTvi) was higher in cases compared to controls (P = 0.01). The ratio of LF/HF of R-R interval which is an index of sympathovagal tone was significantly more in cases compared to controls (P = 0.02). The difference in the left minus the right ABI was significant between cases and controls (P = 0.03). Conclusions: The cases had lower parasympathetic activity as compared to controls, and there was a predominance of sympathetic activity in cases. QTvi may be an important noninvasive tool in this group of patients to study the risk of cardiovascular mortality. PMID:27730068

  13. Effects of aerobic exercise training on cognitive function and cortical vascularity in monkeys.

    PubMed

    Rhyu, I J; Bytheway, J A; Kohler, S J; Lange, H; Lee, K J; Boklewski, J; McCormick, K; Williams, N I; Stanton, G B; Greenough, W T; Cameron, J L

    2010-06-02

    This study examined whether regular exercise training, at a level that would be recommended for middle-aged people interested in improving fitness could lead to improved cognitive performance and increased blood flow to the brain in another primate species. Adult female cynomolgus monkeys were trained to run on treadmills for 1 h a day, 5 days a week, for a 5 month period (n=16; 1.9+/-0.4 miles/day). A sedentary control group sat daily on immobile treadmills (n=8). Half of the runners had an additional sedentary period for 3 months at the end of the exercise period (n=8). In all groups, half of the monkeys were middle-aged (10-12 years old) and half were more mature (15-17 years old). Starting the fifth week of exercise training, monkeys underwent cognitive testing using the Wisconsin General Testing Apparatus (WGTA). Regardless of age, the exercising group learned to use the WGTA significantly faster (4.6+/-3.4 days) compared to controls (8.3+/-4.8 days; P=0.05). At the end of 5 months of running monkeys showed increased fitness, and the vascular volume fraction in the motor cortex in mature adult running monkeys was increased significantly compared to controls (P=0.029). However, increased vascular volume did not remain apparent after a 3-month sedentary period. These findings indicate that the level of exercise associated with improved fitness in middle-aged humans is sufficient to increase both the rate of learning and blood flow to the cerebral cortex, at least during the period of regular exercise.

  14. Lower urinary tract symptoms/benign prostatic hypertrophy and vascular function: Role of the nitric oxide-phosphodiesterase type 5-cyclic guanosine 3',5'-monophosphate pathway.

    PubMed

    Higashi, Yukihito

    2017-03-22

    It is well known that there is an association of lower urinary tract symptoms/benign prostatic hypertrophy with cardiovascular disease, suggesting that lower urinary tract symptoms/benign prostatic hypertrophy is a risk factor for cardiovascular events. Vascular function, including endothelial function and vascular smooth muscle function, is involved in the pathogenesis, maintenance and development of atherosclerosis, leading to cardiovascular events. Vascular dysfunction per se should also contribute to lower urinary tract symptoms/benign prostatic hypertrophy. Both lower urinary tract symptoms/benign prostatic hypertrophy and vascular dysfunction have cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes mellitus, aging, obesity and smoking. Inactivation of the phosphodiesterase type 5-cyclic guanosine 3',5'-monophosphate-nitric oxide pathway causes lower urinary tract symptoms/benign prostatic hypertrophy through an enhancement of sympathetic nervous activity, endothelial dysfunction, increase in Rho-associated kinase activity and vasoconstriction, and decrease in blood flow of pelvic viscera. Both endogenous nitric oxide and exogenous nitric oxide act as vasodilators on vascular smooth muscle cells through an increase in the content of cyclic guanosine 3',5'-monophosphate, which is inactivated by phosphodiesterase type 5. In a clinical setting, phosphodiesterase type 5 inhibitors are widely used in patients with lower urinary tract symptoms/benign prostatic hypertrophy. Phosphodiesterase type 5 inhibitors might have beneficial effects on vascular function through not only inhibition of cyclic guanosine 3',5'-monophosphate degradation, but also increases in testosterone levels and nitric oxide bioavailability, increase in the number and improvement of the function of endothelial progenitor cells, and decrease in insulin resistance. In the present review, the relationships between lower urinary tract symptoms/benign prostatic hypertrophy, the

  15. Increasing functional modularity with residence time in the co-distribution of native and introduced vascular plants.

    PubMed

    Hui, Cang; Richardson, David M; Pyšek, Petr; Le Roux, Johannes J; Kučera, Tomáš; Jarošík, Vojtěch

    2013-01-01

    Species gain membership of regional assemblages by passing through multiple ecological and environmental filters. To capture the potential trajectory of structural changes in regional meta-communities driven by biological invasions, one can categorize species pools into assemblages of different residence times. Older assemblages, having passed through more environmental filters, should become more functionally ordered and structured. Here we calculate the level of compartmentalization (modularity) for three different-aged assemblages (neophytes, introduced after 1500 AD; archaeophytes, introduced before 1500 AD, and natives), including 2,054 species of vascular plants in 302 reserves in central Europe. Older assemblages are more compartmentalized than younger ones, with species composition, phylogenetic structure and habitat characteristics of the modules becoming increasingly distinctive. This sheds light on two mechanisms of how alien species are functionally incorporated into regional species pools: the settling-down hypothesis of diminishing stochasticity with residence time, and the niche-mosaic hypothesis of inlaid neutral modules in regional meta-communities.

  16. In vivo vascularization of MSC-loaded porous hydroxyapatite constructs coated with VEGF-functionalized collagen/heparin multilayers

    NASA Astrophysics Data System (ADS)

    Jin, Kai; Li, Bo; Lou, Lixia; Xu, Yufeng; Ye, Xin; Yao, Ke; Ye, Juan; Gao, Changyou

    2016-01-01

    Rapid and adequate vascularization is vital to the long-term success of porous orbital enucleation implants. In this study, porous hydroxyapatite (HA) scaffolds coated with vascular endothelial growth factor (VEGF)-functionalized collagen (COL)/heparin (HEP) multilayers (porosity 75%, pore size 316.8 ± 77.1 μm, VEGF dose 3.39 ng/mm3) were fabricated to enhance vascularization by inducing the differentiation of mesenchymal stem cells (MSCs) to endothelial cells. The in vitro immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting results demonstrated that the expression of the endothelial differentiation markers CD31, Flk-1, and von Willebrand factor (vWF) was significantly increased in the HA/(COL/HEP)5/VEGF/MSCs group compared with the HA/VEGF/MSCs group. Moreover, the HA/(COL/HEP)5 scaffolds showed a better entrapment of the MSCs and accelerated cell proliferation. The in vivo assays showed that the number of newly formed vessels within the constructs after 28 d was significantly higher in the HA/(COL/HEP)5/VEGF/MSCs group (51.9 ± 6.3/mm2) than in the HA (26.7 ± 2.3/mm2) and HA/VEGF/MSCs (38.2 ± 2.4/mm2) groups. The qRT-PCR and western blotting results demonstrated that the HA/(COL/HEP)5/VEGF/MSCs group also had the highest expression of CD31, Flk-1, and vWF at both the mRNA and protein levels.

  17. In vivo vascularization of MSC-loaded porous hydroxyapatite constructs coated with VEGF-functionalized collagen/heparin multilayers

    PubMed Central

    Jin, Kai; Li, Bo; Lou, Lixia; Xu, Yufeng; Ye, Xin; Yao, Ke; Ye, Juan; Gao, Changyou

    2016-01-01

    Rapid and adequate vascularization is vital to the long-term success of porous orbital enucleation implants. In this study, porous hydroxyapatite (HA) scaffolds coated with vascular endothelial growth factor (VEGF)-functionalized collagen (COL)/heparin (HEP) multilayers (porosity 75%, pore size 316.8 ± 77.1 μm, VEGF dose 3.39 ng/mm3) were fabricated to enhance vascularization by inducing the differentiation of mesenchymal stem cells (MSCs) to endothelial cells. The in vitro immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting results demonstrated that the expression of the endothelial differentiation markers CD31, Flk-1, and von Willebrand factor (vWF) was significantly increased in the HA/(COL/HEP)5/VEGF/MSCs group compared with the HA/VEGF/MSCs group. Moreover, the HA/(COL/HEP)5 scaffolds showed a better entrapment of the MSCs and accelerated cell proliferation. The in vivo assays showed that the number of newly formed vessels within the constructs after 28 d was significantly higher in the HA/(COL/HEP)5/VEGF/MSCs group (51.9 ± 6.3/mm2) than in the HA (26.7 ± 2.3/mm2) and HA/VEGF/MSCs (38.2 ± 2.4/mm2) groups. The qRT-PCR and western blotting results demonstrated that the HA/(COL/HEP)5/VEGF/MSCs group also had the highest expression of CD31, Flk-1, and vWF at both the mRNA and protein levels. PMID:26794266

  18. Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.

    PubMed

    Dan Cao; Yingjie Li; Ling Wei; Yingying Tang

    2016-08-01

    Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.

  19. Factors affecting the development of lung function in Tunisian children.

    PubMed

    Trabelsi, Y; Pariès, J; Harrabi, I; Zbidi, A; Tabka, Z; Richalet, J P; Buvry, A

    2008-01-01

    We undertook to evaluate the impacts of morphology at birth, physical activity, anthropometric, socioeconomic and environmental factors on lung function in healthy Tunisian children. Pulmonary function parameters were measured with a Minato portable spirometer in a randomized population of 756 healthy children (388 males and 368 females) aged between 6 and 16. The morphology at birth, the gestational age, the physical activity, the socioeconomic status, the type of habitation, and the environmental factors were all assessed by a standard questionnaire. Using univariate analysis, we found that: (1) morphometric parameters (height, weight, maximal inspiratory, and expiratory perimeter), as well as sex were highly associated with pulmonary function parameters; (2) Height at birth showed strong significant relations with FVC, FEV(1), and FEV(1)/FVC; (3) lung function parameters were influenced by physical training of our children, socioeconomic status, indoor pollution, and passive smoking; and (4) we did not observe any association between the gestational age and the weight at their birth and lung function parameters. Using a general linear model analysis, morphometric parameters, age, sex, type of heating, and maximal inspiratory and expiratory perimeters had significant relation with respiratory parameters. In our population of healthy Tunisian children, the main predictive factors of the pulmonary development were the morphological factors such as height, weight, maximal inspiratory, and expiratory thoracic perimeter, sex and age, and the environmental conditions such as type of heating but not morphology at birth, physical activity, or socioeconomic status.

  20. TGF-beta and TNF-a affect cell surface proteoglycan and sialic acid expression on vascular endothelial cells.

    PubMed

    Doiron, Amber L; Kirkpatrick, Allison P; Rinker, Kristina D

    2004-01-01

    Atherosclerosis is the formation of plaques in the arterial wall brought about by numerous events including the accumulation of oxidized low density lipoprotein (LDL), stimulation of inflammatory responses, the release of cytokines, and the attachment of monocytes to the arterial wall. Proteoglycans are implicated in many aspects of atherosclerosis including the metabolism of lipoproteins, regulation of cytokine activity, cell adhesion, and modification of the extracellular matrix. Due to their complex role in molecular recognition and cellular adhesion, the glycosaminoglycan (GAG) chains attached to the proteoglycan core and sialic acids on the terminal ends of the glycan chains are of interest. This study investigated the effects of exposure to transforming growth factor-beta 1 (TGF-beta 1) and tumor necrosis factor-a (TNF-a) on the expression of cell surface GAGs and sialic acids on human umbilical vein endothelial cells (HUVECs). Initial results show that TGF-beta 1 affected GAG expression compared to a control condition. Results also show that the combination of TGF-beta 1 and TNF-a affected GAG expression differently than does TGF-beta 1 alone. Additionally, TNF-a decreased the number of sialic acid residues per cell and TGF-beta 1 slightly upregulated sialic acid expression as compared to the control. The combination of the two cytokines showed a larger upward trend in this value. These data indicate that TNF-a and TGF-beta 1 play a role in the expression of GAG chains and sialic acids on the cell surface. Further study may clarify the implications of these findings for atherosclerosis.

  1. Drying process strongly affects probiotics viability and functionalities.

    PubMed

    Iaconelli, Cyril; Lemetais, Guillaume; Kechaou, Noura; Chain, Florian; Bermúdez-Humarán, Luis G; Langella, Philippe; Gervais, Patrick; Beney, Laurent

    2015-11-20

    Probiotic formulations are widely used and are proposed to have a variety of beneficial effects, depending on the probiotic strains present in the product. The impact of drying processes on the viability of probiotics is well documented. However, the impact of these processes on probiotics functionality remains unclear. In this work, we investigated variations in seven different bacterial markers after various desiccation processes. Markers were composed of four different viability evaluation (combining two growth abilities and two cytometric measurements) and in three in vitro functionalities: stimulation of IL-10 and IL-12 production by PBMCs (immunomodulation) and bacterial adhesion to hexadecane. We measured the impact of three drying processes (air-drying, freeze-drying and spray-drying), without the use of protective agents, on three types of probiotic bacteria: Bifidobacterium bifidum, Lactobacillus plantarum and Lactobacillus zeae. Our results show that the bacteria respond differently to the three different drying processes, in terms of viability and functionality. Drying methods produce important variations in bacterial immunomodulation and hydrophobicity, which are correlated. We also show that adherence can be stimulated (air-drying) or inhibited (spray-drying) by drying processes. Results of a multivariate analysis show no direct correlation between bacterial survival and functionality, but do show a correlation between probiotic responses to desiccation-rewetting and the process used to dry the bacteria.

  2. Can Particulate Pollution Affect Lung Function in Healthy Adults?

    EPA Science Inventory

    Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

  3. Chemical Modifications that Affect Nutritional and Functional Properties of Proteins.

    ERIC Educational Resources Information Center

    Richardson, T.; Kester, J. J.

    1984-01-01

    Discusses chemical alterations of selected amino acids resulting from environmental effects (photooxidations, pH extremes, thermally induced effects). Also dicusses use of intentional chemical derivatizations of various functional groups in amino acid residue side chains and how recombinant DNA techniques might be useful in structure/function…

  4. Metabolic and vascular origins of the BOLD effect: Implications for imaging pathology and resting-state brain function.

    PubMed

    Mark, Clarisse I; Mazerolle, Erin L; Chen, J Jean

    2015-08-01

    The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes in blood oxygenation resulting from the relative balance between cerebral oxygen metabolism (through neural activity) and oxygen supply (through cerebral blood flow and volume). As such, there are cases in which BOLD signals might be dissociated from neural activity, leading to misleading results. The emphasis of this review is to develop a critical perspective for interpreting BOLD results, through a comprehensive consideration of BOLD's metabolic and vascular underpinnings. We demonstrate that such an understanding is especially important under disease or resting conditions. We also describe state-of-the-art acquisition and analytical techniques to reveal physiological information on the mechanisms underlying measured BOLD signals. With these goals in mind, this review is structured to provide a fundamental understanding of: 1) the physiological and physical sources of the BOLD contrast; 2) the extraction of information regarding oxidative metabolism and cerebrovascular reactivity from the BOLD signal, critical to investigating neuropathology; and 3) the fundamental importance of metabolic and vascular mechanisms for interpreting resting-state BOLD measurements.

  5. Alteration of Contractile Function and Calcium Ion Movements in Vascular Smooth Muscle by Gentamicin and Other Aminoglycoside Antibiotics

    PubMed Central

    Adams, H. Richard; Goodman, Frank R.; Weiss, George B.

    1974-01-01

    Experiments were conducted to examine the effects of certain aminoglycoside antibiotics on contractile responses and related calcium ion (Ca2+) movements in isolated vascular smooth muscle. Gentamicin, kanamycin, and streptomycin decreased contractile responses produced by norepinephrine, histamine, and high K+ in rabbit aortic strips. The inhibitory action of these antibiotics on mechanical function was more pronounced when the Ca2+ concentration of the bathing solution was decreased from 1.5 mM (normal Ca2+ solution) to 0.05 mM (low Ca2+ solution). The uptake of radiocalcium (45Ca) into the isolated media-intimal layer of rabbit aortae was decreased in a maintained manner by each antibiotic. With gentamicin, the inhibitory effect on 45Ca uptake was shown to be dependent upon the concentration of gentamicin employed and to be more evident in a 0.1 mM Ca2+ solution than in a normal Ca2+ solution. In addition, the rate of 45Ca efflux from the rabbit aortic media-intimal layer was increased in a sustained manner by gentamicin, streptomycin, and kanamycin. Furthermore, contractile responses induced by high K+ and norepinephrine in canine carotid arterial strips were inhibited by gentamicin. Present findings indicate that aminoglycoside antibiotics interfere with Ca2+-linked events leading to activation of the contractile mechanism of vascular smooth muscle. These in vitro findings may partially explain the occurrence of in vivo cardiovascular depression that has occasionally been observed after the administration of chemically related antimicrobial agents. PMID:15825418

  6. Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria

    PubMed Central

    Mantel, Pierre-Yves; Hjelmqvist, Daisy; Walch, Michael; Kharoubi-Hess, Solange; Nilsson, Sandra; Ravel, Deepali; Ribeiro, Marina; Grüring, Christof; Ma, Siyuan; Padmanabhan, Prasad; Trachtenberg, Alexander; Ankarklev, Johan; Brancucci, Nicolas M.; Huttenhower, Curtis; Duraisingh, Manoj T.; Ghiran, Ionita; Kuo, Winston P.; Filgueira, Luis; Martinelli, Roberta; Marti, Matthias

    2016-01-01

    Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection. PMID:27721445

  7. Vascular function measured by fingertip thermal reactivity is impaired in patients with metabolic syndrome and diabetes mellitus.

    PubMed

    Ahmadi, Naser; Hajsadeghi, Fereshteh; Gul, Khawar; Leibfried, Michael; DeMoss, Daniel; Lee, Robert; Flores, Ferdinand; Nasir, Khurram; Hecht, Harvey; Naghavi, Morteza; Budoff, Matthew J

    2009-11-01

    Digital thermal monitoring (DTM) of vascular function has already been shown to correlate well with coronary artery calcium (CAC) score and coronary artery disease. To determine its utility in the metabolic syndrome (MS) and diabetes mellitus (DM), 233 asymptomatic patients with DM/MS but without coronary artery disease underwent DTM during and after 5 minutes of supra-systolic arm cuff inflation, as well as CAC. Post-cuff deflation adjusted temperature rebound (aTR) was lower in MS and DM compared with the normal group. The odds ratio of lowest vs upper 2 tertiles of aTR was 2.3 for MS and 3.5 for DM compared with the normal group, independent of age, sex, and risk factors. The area under the receiver operating characteristic curve to predict CAC > or =100 was 0.69 for metabolic status (DM/MS), 0.79 for aTR, and 0.87 for both. This study demonstrates that vascular dysfunction measured by DTM is associated with DM/MS and could potentially be used to detect asymptomatic individuals with increased subclinical atherosclerosis.

  8. Vascularized Thoracodorsal to Suprascapular Nerve Transfer, a Novel Technique to Restore Shoulder Function in Partial Brachial Plexopathy

    PubMed Central

    Potter, Shirley M.; Ferris, Scott I.

    2016-01-01

    We describe the clinical outcome of a novel nerve transfer to restore active shoulder motion in upper brachial plexus injury. The thoracodorsal nerve (TDN) was successfully used as a vascularized donor nerve to neurotize to the suprascapular nerve (SSN) in a patient with limited donor nerve availability. At 4 years follow-up, he had regained useful external rotation of the injured limb, with no significant donor site morbidity. Shoulder abduction return was less impressive, however, and reasons for this are discussed. We provide a comprehensive review of the literature on this topic and a subsequent discussion on the details of this novel technique. This is the first reported case of TDN to SSN transfer, and also the first reported case of a vascularized TDN transfer in the English language literature. We advocate direct thoracodorsal to SSN transfer as a valid surgical option for the restoration of shoulder function in patients with partial brachial plexus avulsion, when conventional nerve donors are unavailable. PMID:27014699

  9. Development of affective theory of mind across adolescence: disentangling the role of executive functions.

    PubMed

    Vetter, Nora C; Altgassen, Mareike; Phillips, Louise; Mahy, Caitlin E V; Kliegel, Matthias

    2013-01-01

    Theory of mind, the ability to understand mental states, involves inferences about others' cognitive (cognitive theory of mind) and emotional (affective theory of mind) mental states. The current study explored the role of executive functions in developing affective theory of mind across adolescence. Affective theory of mind and three subcomponents of executive functions (inhibition, updating, and shifting) were measured. Affective theory of mind was positively related to age, and all three executive functions. Specifically, inhibition explained the largest amount of variance in age-related differences in affective theory of mind.

  10. Alginate Overproduction Affects Pseudomonas aeruginosa Biofilm Structure and Function

    PubMed Central

    Hentzer, Morten; Teitzel, Gail M.; Balzer, Grant J.; Heydorn, Arne; Molin, Søren; Givskov, Michael; Parsek, Matthew R.

    2001-01-01

    During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them is at the present unclear. In this study, we report that the overproduction of alginate affects biofilm development on an abiotic surface. Biofilms formed by an alginate-overproducing strain exhibit a highly structured architecture and are significantly more resistant to the antibiotic tobramycin than a biofilm formed by an isogenic nonmucoid strain. These results suggest that an important consequence of the conversion to mucoidy is an altered biofilm architecture that shows increasing resistance to antimicrobial treatments. PMID:11514525

  11. Nuclear cyclophilins affect spliceosome assembly and function in vitro.

    PubMed

    Adams, B M; Coates, Miranda N; Jackson, S RaElle; Jurica, Melissa S; Davis, Tara L

    2015-07-15

    Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing.

  12. Prenatal Drug Exposure Affects Neonatal Brain Functional Connectivity

    PubMed Central

    Salzwedel, Andrew P.; Vachet, Clement; Gerig, Guido; Lin, Weili

    2015-01-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala–frontal, insula–frontal, and insula–sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala–frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention. PMID:25855194

  13. How optimization of potential functions affects protein folding.

    PubMed Central

    Hao, M H; Scheraga, H A

    1996-01-01

    The relationship between the optimization of the potential function and the foldability of theoretical protein models is studied based on investigations of a 27-mer cubic-lattice protein model and a more realistic lattice model for the protein crambin. In both the simple and the more complicated systems, optimization of the energy parameters achieves significant improvements in the statistical-mechanical characteristics of the systems and leads to foldable protein models in simulation experiments. The foldability of the protein models is characterized by their statistical-mechanical properties--e.g., by the density of states and by Monte Carlo folding simulations of the models. With optimized energy parameters, a high level of consistency exists among different interactions in the native structures of the protein models, as revealed by a correlation function between the optimized energy parameters and the native structure of the model proteins. The results of this work are relevant to the design of a general potential function for folding proteins by theoretical simulations. PMID:8643516

  14. Does caregiving stress affect cognitive function in older women?

    PubMed

    Lee, Sunmin; Kawachi, Ichiro; Grodstein, Francine

    2004-01-01

    Increasing numbers of women provide care to their ill spouses; however, no studies have examined possible effects of caregiving stress on cognitive function. We administered 6 tests of cognitive function to 13740 Nurses' Health Study participants aged 70-79 years. We collected information on caregiving and numerous potential confounding variables via biennial mailed questionnaires. After adjustment for potential confounders (age, education, mental health index, vitality index, use of antidepressants, and history of high blood pressure, diabetes, and heart disease), we found modest but significantly increased risks of low cognitive function on three of the cognitive tests among women who provided care to a disabled or ill spouse compared with women who did not provide any care. For example, on the TICS, a test of general cognition, the risk of a low score was 31% higher in women who provided care compared with women who did not (RR = 1.31, 95% CI 1.10, 1.56). We found a moderately increased risk of poor performance on several cognitive tests among women who provided care to their disabled or ill husbands.

  15. Microplastics Affect the Ecological Functioning of an Important Biogenic Habitat.

    PubMed

    Green, Dannielle Senga; Boots, Bas; O'Connor, Nessa E; Thompson, Richard

    2017-01-03

    Biological effects of microplastics on the health of bivalves have been demonstrated elsewhere, but ecological impacts on the biodiversity and ecosystem functioning of bivalve-dominated habitats are unknown. Thus, we exposed intact sediment cores containing European flat oysters (Ostrea edulis) or blue mussels (Mytilus edulis) in seawater to two different densities (2.5 or 25 μg L(-1)) of biodegradable or conventional microplastics in outdoor mesocosms. We hypothesized that filtration rates of the bivalves, inorganic nitrogen cycling, primary productivity of sediment dwelling microphytobenthos, and the structure of invertebrate benthic assemblages would be influenced by microplastics. After 50 days, filtration by M. edulis was significantly less when exposed to 25 μg L(-1) of either type of microplastics, but there were no effects on ecosystem functioning or the associated invertebrate assemblages. Contrastingly, filtration by O. edulis significantly increased when exposed to 2.5 or 25 μg L(-1) of microplastics, and porewater ammonium and biomass of benthic cyanobacteria decreased. Additionally the associated infaunal invertebrate assemblages differed, with significantly less polychaetes and more oligochaetes in treatments exposed to microplastics. These findings highlight the potential of microplastics to impact the functioning and structure of sedimentary habitats and show that such effects may depend on the dominant bivalve present.

  16. Nuclear cyclophilins affect spliceosome assembly and function in vitro

    PubMed Central

    Adams, B.M.; Coates, Miranda N.; Jackson, S. RaElle; Jurica, Melissa S.; Davis, Tara L.

    2015-01-01

    Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing. PMID:25967372

  17. Role of 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of vascular function in a model of hypertension and endothelial dysfunction.

    PubMed

    Yousif, Mariam H M; Benter, Ibrahim F

    2010-01-01

    The objective of this study was to determine if acute inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis or reduced inactivation of epoxyeicosatrienoic acids (EETs) can correct L-N(G)-nitro-arginine-methyl-ester (L-NAME)-induced abnormal vascular reactivity in the perfused mesenteric bed and the carotid artery of spontaneously hypertensive rats (SHR). Administration of L-NAME in drinking water (80 mg/l) to SHR for 3 weeks resulted in abnormal vascular reactivity to norepinephrine and carbachol in the perfused mesenteric vascular bed and carotid artery, and significantly elevated mean arterial blood pressure (244 +/- 9 mm Hg) as compared to SHR controls drinking regular water (176 +/- 3 mm Hg). In the perfused mesenteric vascular bed, the impaired vascular responsiveness to norepinephrine was corrected by acute treatment with N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine (HET0016), an inhibitor of 20-HETE formation, but not by 1-cyclohexyl-3-dodecyl urea (CDU), an inhibitor of soluble epoxide hydrolase. Treatment with either HET0016 or CDU did not improve impaired carbachol-induced vasodilation in the perfused mesenteric vascular bed. In the isolated carotid artery, treatment with HET0016 corrected the L-NAME-induced increase in norepinephrine-induced vasoconstriction, whereas only CDU treatment could improve impaired carbachol-induced vasodilation. Results of this study indicate that vascular function in a state of compromised nitric oxide formation is differentially modulated by 20-HETE and EETs, and that treatment with HET0016 or CDU may improve vascular function in a state of high blood pressure and endothelial dysfunction.

  18. [The role of vascular endothelial growth factor in the regulation of development and functioning of the brain: new target molecules for pharmacotherapy].

    PubMed

    Roslavtceva, V V; Salmina, A B; Prokopenko, S V; Pozhilenkova, E A; Kobanenko, I V; Rezvitskaya, G G

    2016-01-01

    Vascular endothelial growth factors (VEGFs) have been shown to participate in atherosclerosis, arteriogenesis, cerebral edema, neuroprotection, neurogenesis, angiogenesis, postischemic brain and vessel repair. Most of these actions involve VEGF-A and the VEGFR-2 receptor. VEGF signaling pathways represent an important potential for treatment of neurological diseases affecting the brain.

  19. Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex

    PubMed Central

    Fisher, Oriana S.; Deng, Hanqiang; Liu, Dou; Zhang, Ya; Wei, Rong; Deng, Yong; Zhang, Fan; Louvi, Angeliki; Turk, Benjamin E.; Boggon, Titus J.; Su, Bing

    2015-01-01

    Cerebral cavernous malformations 2 (CCM2) loss is associated with the familial form of CCM disease. The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. Here we report that Mekk3 plays an intrinsic role in embryonic vascular development. Inducible endothelial Mekk3 knockout in neonatal mice is lethal due to multiple intracranial haemorrhages and brain blood vessels leakage. We discover direct interaction between CCM2 harmonin homology domain (HHD) and the N terminus of MEKK3, and determine a 2.35 Å cocrystal structure. We find Mekk3 deficiency impairs neurovascular integrity, which is partially dependent on Rho–ROCK signalling, and that disruption of MEKK3:CCM2 interaction leads to similar neurovascular leakage. We conclude that CCM2:MEKK3-mediated regulation of Rho signalling is required for maintenance of neurovascular integrity, unravelling a mechanism by which CCM2 loss leads to disease. PMID:26235885

  20. Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex

    SciTech Connect

    Fisher, Oriana S.; Deng, Hanqiang; Liu, Dou; Zhang, Ya; Wei, Rong; Deng, Yong; Zhang, Fan; Louvi, Angeliki; Turk, Benjamin E.; Boggon, Titus J.; Su, Bing

    2015-08-03

    Cerebral cavernous malformations 2 (CCM2) loss is associated with the familial form of CCM disease. The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. Here we report that Mekk3 plays an intrinsic role in embryonic vascular development. Inducible endothelial Mekk3 knockout in neonatal mice is lethal due to multiple intracranial haemorrhages and brain blood vessels leakage. We discover direct interaction between CCM2 harmonin homology domain (HHD) and the N terminus of MEKK3, and determine a 2.35 Å cocrystal structure. We find Mekk3 deficiency impairs neurovascular integrity, which is partially dependent on Rho–ROCK signalling, and that disruption of MEKK3:CCM2 interaction leads to similar neurovascular leakage. We conclude that CCM2:MEKK3-mediated regulation of Rho signalling is required for maintenance of neurovascular integrity, unravelling a mechanism by which CCM2 loss leads to disease.

  1. Endothelial Microparticle-Derived Reactive Oxygen Species: Role in Endothelial Signaling and Vascular Function

    PubMed Central

    Burger, Dylan; Turner, Maddison; Munkonda, Mercedes N.; Touyz, Rhian M.

    2016-01-01

    Endothelial microparticles are effectors of endothelial damage; however mechanisms involved are unclear. We examined the effects of eMPs on cultured endothelial cells (ECs) and isolated vessels and investigated the role of eMP-derived reactive oxygen species (ROS) and redox signaling in these processes. eMPs were isolated from EC media and their ability to directly produce ROS was assessed by lucigenin and liquid chromatography. Nicotinamide adenine dinucleotide phosphate oxidase (Nox) subunits were probed by Western blot. ECs were treated with eMPs and effects on kinase signaling, superoxide anion (O2∙−) generation, and nitric oxide (NO) production were examined. Acetylcholine-mediated vasorelaxation was assessed by myography in eMP-treated mesenteric arteries. eMPs contained Nox1, Nox2, Nox4, p47phox, p67phox, and p22phox and they produced ROS which was inhibited by the Nox inhibitor, apocynin. eMPs increased phosphorylation of ERK1/2 and Src, increased O2∙− production, and decreased A23187-induced NO production in ECs. Pretreatment of eMPs with apocynin diminished eMP-mediated effects on ROS and NO production but had no effect on eMP-mediated kinase activation or impairment in vasorelaxation. Our findings identify a novel mechanism whereby eMP-derived ROS contributes to MP bioactivity. These interactions may be important in conditions associated with vascular injury and increased eMP formation. PMID:27313830

  2. Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans

    PubMed Central

    Perkins, Jennifer M.; Joy, Nino G.; Tate, Donna B.

    2015-01-01

    We investigated the separate and combined effects of hyperglycemia and hyperinsulinemia on markers of endothelial function, proinflammatory and proatherothrombotic responses in overweight/obese nondiabetic humans. Twenty-two individuals (13 F/9 M, BMI 30.1 ± 4.1 kg/m2) were studied during four randomized, single-blind protocols. The pancreatic clamp technique was combined with 4-h glucose clamps consisting of either 1) euinsulinemia-euglycemia, 2) euinsulinemia-hyperglycemia, 3) hyperinsulinemia-hyperglycemia, or 4) hyperinsulinemia-euglycemia. Insulin levels were higher (998 ± 66 vs. 194 ± 22 pmol/l) during hyperinsulinemia compared with euinsulinemia. Glucose levels were 11.1 mmol/l during hyperinsulinemia compared with 5.1 ± 0.1 mmol/l during euglycemia. VCAM, ICAM, P-selectin, E-selectin, IL-6, adiponectin, and PAI-1 responses were all increased (P < 0.01-0.0001), and endothelial function was decreased (P < 0.0005) during euinsulinemia-hyperglycemia compared with other protocols. Hyperinsulinemia in the presence of hyperglycemia prevented the increase in proinflammatory and proatherothrombotic markers while also normalizing vascular endothelial function. We conclude that 4 h of moderate hyperglycemia can result in increases of proinflammatory markers (ICAM, VCAM, IL-6, E-selectin), platelet activation (P-selectin), reduced fibrinolytic balance (increased PAI-1), and disordered endothelial function in a group of obese and overweight individuals. Hyperinsulinemia prevents the actions of moderate hyperglycemia to reduce endothelial function and increase proinflammatory and proatherothrombotic markers. PMID:26015434

  3. Visual function affects prosocial behaviors in older adults.

    PubMed

    Teoli, Dac A; Smith, Merideth D; Leys, Monique J; Jain, Priyanka; Odom, J Vernon

    2016-02-01

    Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration commonly lead to decreased peripheral/central field, decreased visual acuity, and increased functional disability. We sought to answer if relationships exist between measures of visual function and reported prosocial behaviors in an older adult population with eye-related diagnoses. The sample consisted of adults, aged ≥ 60 years old, at an academic hospital's eye institute. Vision ranged from normal to severe impairment. Medical charts determined the visual acuities, ocular disease, duration of disease (DD), and visual fields (VF). Measures of giving help were via validated questionnaires on giving formal support (GFS) and giving informal support; measures of help received were perceived support (PS) and informal support received (ISR). ISR had subscales: tangible support (ISR-T), emotional support (ISR-E), and composite (ISR-C). Visual acuities of the better and worse seeing eyes were converted to LogMAR values. VF information converted to a 4-point rating scale of binocular field loss severity. DD was in years. Among 96 participants (mean age 73.28; range 60-94), stepwise regression indicated a relationship of visual variables to GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p < 0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05; Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related conditions can impact levels and perceptions of support exchanges. Our data reinforces the importance of visual function as an influence on prosocial behavior in older adults.

  4. Affected functional networks associated with sentence production in classic galactosemia.

    PubMed

    Timmers, Inge; van den Hurk, Job; Hofman, Paul Am; Zimmermann, Luc Ji; Uludağ, Kâmil; Jansma, Bernadette M; Rubio-Gozalbo, M Estela

    2015-08-07

    Patients with the inherited metabolic disorder classic galactosemia have language production impairments in several planning stages. Here, we assessed potential deviations in recruitment and connectivity across brain areas responsible for language production that may explain these deficits. We used functional magnetic resonance imaging (fMRI) to study neural activity and connectivity while participants carried out a language production task. This study included 13 adolescent patients and 13 age- and gender-matched healthy controls. Participants passively watched or actively described an animated visual scene using two conditions, varying in syntactic complexity (single words versus a sentence). Results showed that patients recruited additional and more extensive brain regions during sentence production. Both groups showed modulations with syntactic complexity in left inferior frontal gyrus (IFG), a region associated with syntactic planning, and in right insula. In addition, patients showed a modulation with syntax in left superior temporal gyrus (STG), whereas the controls did not. Further, patients showed increased activity in right STG and right supplementary motor area (SMA). The functional connectivity data showed similar patterns, with more extensive connectivity with frontal and motor regions, and restricted and weaker connectivity with superior temporal regions. Patients also showed higher baseline cerebral blood flow (CBF) in right IFG and trends towards higher CBF in bilateral STG, SMA and the insula. Taken together, the data demonstrate that language abnormalities in classic galactosemia are associated with specific changes within the language network. These changes point towards impairments related to both syntactic planning and speech motor planning in these patients.

  5. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    NASA Astrophysics Data System (ADS)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-02-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  6. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    NASA Astrophysics Data System (ADS)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-01-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  7. Restricted Blood Flow Exercise in Sedentary, Overweight African-American Females May Increase Muscle Strength and Decrease Endothelial Function and Vascular Autoregulation

    PubMed Central

    Bond, Vernon; Curry, Bryan Heath; Kumar, Krishna; Pemminati, Sudhakar; Gorantla, Vasavi Rakesh; Kadur, Kishan; Millis, Richard Mark

    2017-01-01

    Objectives: Exercise with partially restricted blood flow is a low-load, low-intensity resistance training regimen which may have the potential to increase muscle strength in the obese, elderly and frail who are unable to do high-load training. Restricted blood flow exercise has also been shown to affect blood vessel function variably and can, therefore, contribute to blood vessel dysfunction. This pilot study tests the hypothesis that unilateral resistance training of the leg extensors with partially restricted blood flow increases muscle strength and decreases vascular autoregulation. Methods: The subjects were nine normotensive, overweight, young adult African-Americans with low cardiorespiratory fitness who underwent unilateral training of the quadriceps’ femoris muscles with partially restricted blood flow at 30% of the 1-repetition maximum (1-RM) load for 3 weeks. The 1-RM load and post-occlusion blood flow to the lower leg (calf) were measured during reactive hyperemia. Results: The 1-RM load increased in the trained legs from 77 ± 3 to 84 ± 4 kg (P < 0.05) in the absence of a significant effect on the 1-RM load in the contralateral untrained legs (P > 0.1). Post-occlusion blood flow decreased significantly in the trained legs from 19 ± 2 to 13 ± 2 mL· min-1· dL-1 (P < 0.05) and marginally in the contralateral untrained legs from 18 ± 2 to 16 ± 1 mL· min-1· dL-1 (P = 0.09). Changes in post-occlusion blood flow to the skin overlying the trained and the contralateral untrained muscles were not significant. Conclusion: These results demonstrate that restricted blood flow exercise, which results in significant gains in muscle strength, may produce decrements in endothelial dysfunction and vascular autoregulation. Future studies should determine whether pharmacopuncture plays a role in treatments for such blood vessel dysfunction. PMID:28392959

  8. Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury.

    PubMed

    Shindo, Akihiro; Liang, Anna C; Maki, Takakuni; Miyamoto, Nobukazu; Tomimoto, Hidekazu; Lo, Eng H; Arai, Ken

    2016-01-01

    Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury.

  9. Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

    PubMed Central

    Shindo, Akihiro; Liang, Anna C; Maki, Takakuni; Miyamoto, Nobukazu; Tomimoto, Hidekazu; Lo, Eng H

    2016-01-01

    Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury. PMID:25920960

  10. [Bone metabolism and cardiovascular function update. Inter-communication between bone marrow hematopoiesis and skeletal/vascular network].

    PubMed

    Katayama, Yoshio

    2014-07-01

    The hematopoiesis takes place in the bone marrow. Because bone marrow is the "marrow" of the bone, bone marrow does not exist without bone. The specialized microenvironment for hematopoietic stem cells (HSCs) to be appropriately functional is called "niche" . In the recent ten years since the bone-forming osteoblast was identified as a HSC niche, the entire mesenchymal lineage cells from mesenchymal stem cells to end-terminal osteocytes have been recognized as niche cells or niche-modulators. Among these, mesenchymal stem/progenitor cells are located at perivascular area. The very recent study showed the difference between arteriolar and sinusoidal niches. It is likely that the vascular network and the bone tissue are connected by the mesenchymal lineage cells as a complex of bone forming system, and HSCs utilize this complex as a series of niche.

  11. Low level methylmercury exposure affects neuropsychological function in adults

    PubMed Central

    Yokoo, Edna M; Valente, Joaquim G; Grattan, Lynn; Schmidt, Sérgio Luís; Platt, Illeane; Silbergeld, Ellen K

    2003-01-01

    -dependent effect. Conclusions This study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures. PMID:12844364

  12. Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

    PubMed

    Cartocci, Veronica; Servadio, Michela; Trezza, Viviana; Pallottini, Valentina

    2017-02-01

    Cholesterol is an important component for cell physiology. It regulates the fluidity of cell membranes and determines the physical and biochemical properties of proteins. In the central nervous system, cholesterol controls synapse formation and function and supports the saltatory conduction of action potential. In recent years, the role of cholesterol in the brain has caught the attention of several research groups since a breakdown of cholesterol metabolism has been associated with different neurodevelopmental and neurodegenerative diseases, and interestingly also with psychiatric conditions. The aim of this review is to summarize the current knowledge about the connection between cholesterol dysregulation and various neurologic and psychiatric disorders based on clinical and preclinical studies. J. Cell. Physiol. 232: 281-286, 2017. © 2016 Wiley Periodicals, Inc.

  13. Does vitamin C deficiency affect cognitive development and function?

    PubMed

    Hansen, Stine Normann; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-09-19

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies.

  14. Enhanced serotonin transporter function during depression in seasonal affective disorder.

    PubMed

    Willeit, Matthäus; Sitte, Harald H; Thierry, Nikolaus; Michalek, Klaus; Praschak-Rieder, Nicole; Zill, Peter; Winkler, Dietmar; Brannath, Werner; Fischer, Michael B; Bondy, Brigitta; Kasper, Siegfried; Singer, Ernst A

    2008-06-01

    Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramine-induced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case-control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p=0.014) and outward (p=0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (rho=0.421, p=0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.

  15. The chronic effects of whey proteins on blood pressure, vascular function, and inflammatory markers in overweight individuals.

    PubMed

    Pal, Sebely; Ellis, Vanessa

    2010-07-01

    Limited evidence suggests that dairy whey protein may be the major dairy component that is responsible for health benefits currently associated with increased dairy consumption. Whey proteins may reduce blood pressure and improve cardiovascular health. This study evaluated the effects of whey protein supplementation on blood pressure, vascular function and inflammatory markers compared to casein and glucose (control) supplementation in overweight/obese individuals. The subjects were randomized to either whey protein, casein or glucose supplementation for 12 weeks according to a parallel design. In all, 70 men and women with a mean (+/-s.e.m.) BMI (kg/m(2)) of 31.3 +/- 0.8 completed the study. Systolic blood pressure (SBP) decreased significantly at week 6 compared to baseline in the whey and casein groups, (P = 0.028 and P = 0.020, respectively) and at week 12 (P = 0.020, and P = 0.017, respectively). Diastolic blood pressure (DBP) decreased significantly compared to baseline in the whey and casein groups (P = 0.038 and P = 0.042, respectively) at week 12. DBP decreased significantly in the whey and casein groups (P = 0.025, P = 0.038, respectively) at week 12 compared to the control group. Augmentation index (AI) was significantly lower from baseline at 12 weeks (P = 0.021) in the whey group. AI decreased significantly in the whey group at 12 weeks compared to control (P = 0.006) and casein (P = 0.006). There were no significant changes in inflammatory markers within or between groups. This study demonstrated that supplementation with whey protein improves blood pressure and vascular function in overweight and obese individuals.

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

    PubMed Central

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

    2014-01-01

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

  17. Cardiac and Vascular Function in Bedrested Volunteers: Effects of Artificial Gravity Training

    NASA Technical Reports Server (NTRS)

    Meng, M.; Platts, S.; Stenger, M.; Diedrich, A.; Schlegel, T.; Natapoff, A.; Knapp, C.; Evans, J.

    2007-01-01

    Cardiovascular effects of an artificial gravity (AG) countermeasure on deconditioned male volunteers were studied. In two groups of men we measured cardiovascular parameters at rest and in response to 30 minutes of 80 deg. head up tilt (HUT) before, at the end of, and four days following 21 days of 6 deg. head down bed rest (HDBR). One group (N=7) underwent no countermeasure while the other (N=8) received a daily, one hour, dose (2.5 gz at the foot, decreasing to 1.0 gz at the heart) of AG training on the Johnson Space Center short radius centrifuge. Cardiovascular parameters measured included heart rate, blood pressure, stroke volume, cardiac output, peripheral vascular resistance, plasma volume shifts, and vasoactive hormones. Untrained subjects exhibited shorter tilt survival (on average 8 minutes shorter) compared to trained subjects. By the end of bed rest, mean heart rate (MHR) was elevated in both groups (both supine and during tilt). In addition, treated subjects demonstrated lower, tilt-induced, increases in MHR four days following HDBR, indicating a more rapid return to pre bed rest conditions. Results from an index of autonomic balance (percentage of MHR spectral power in the respiratory frequency range) in control of heart rate are consistent with the interpretation that parasympathetic nervous system withdrawal was responsible for both tilt- and bed rest-induced increases in MHR. Our data support our pre-study hypothesis that AG treatment would lessen cardiovascular effects of deconditioning in bed rested men and suggest that AG should be further pursued as a space flight countermeasure.

  18. Dark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trial.

    PubMed

    Hammer, Alexandra; Koppensteiner, Renate; Steiner, Sabine; Niessner, Alexander; Goliasch, Georg; Gschwandtner, Michael; Hoke, Matthias

    2015-01-01

    Flavonoid-rich dark chocolate has positive effects on vascular function in healthy subjects and in patients at risk of atherosclerosis. The impact of dark chocolate on endothelial and microvascular function in patients with symptomatic peripheral artery disease (PAD) has not been investigated so far. In an investigator blinded, randomized, controlled, cross-over trial we assessed the effect of flavonoid-rich dark chocolate and cocoa-free control chocolate on flow-mediated dilatation (FMD) of the brachial artery and on microvascular function (assessed by Laser Doppler fluxmetry) in 21 patients with symptomatic (Fontaine stage II) PAD. Measurements were done in each patient on 2 single days, with an interval of 7 days, at baseline and at 2 hours after ingestion of 50 g dark chocolate or 50 g white chocolate, respectively. FMD remained unchanged after intake of dark chocolate (baseline and 2 hours after ingestion, %: 5.1 [IQR 4.4 to 7.3] and 5.5 [IQR 3.9 to 10.4]; p = 0.57, and after intake of white chocolate (baseline and 2 hours after ingestion, %: 6.4 [IQR 4.5 to 11.4] and 4.4 [IQR 2.6 to 8.7]; p = 0.14. Similarly, microcirculatory parameters were not significantly altered after intake of any chocolate compared with the respective baseline values. In conclusion, a single consumption of 50 g dark chocolate has no effect on endothelial and microvascular function in patients with symptomatic PAD.

  19. Urinary CD133+ Extracellular Vesicles Are Decreased in Kidney Transplanted Patients with Slow Graft Function and Vascular Damage

    PubMed Central

    Dimuccio, Veronica; Ranghino, Andrea; Praticò Barbato, Loredana; Fop, Fabrizio; Biancone, Luigi; Camussi, Giovanni; Bussolati, Benedetta

    2014-01-01

    Extracellular vesicles (EVs) present in the urine are mainly released from cells of the nephron and can therefore provide information on kidney function. We here evaluated the presence of vesicles expressing the progenitor marker CD133 in the urine of normal subjects and of patients undergoing renal transplant. We found that EV expressing CD133 were present in the urine of normal subjects, but not of patients with end stage renal disease. The first day after transplant, urinary CD133+ EVs were present at low levels, to increase thereafter (at day 7). Urinary CD133+ EVs significantly increased in patients with slow graft function in respect to those with early graft function. In patients with a severe pre-transplant vascular damage of the graft, CD133+ EVs did not increase at day 7. At variance, the levels of EVs expressing the renal exosomal marker CD24 did not vary in the urine of patients with end stage renal disease or in transplanted patients in respect to controls. Sorted CD133+ EVs were found to express glomerular and proximal tubular markers. These data indicate that urinary CD133+ EVs are continuously released during the homeostatic turnover of the nephron and may provide information on its function or regenerative potential. PMID:25100147

  20. Neurology of Affective Prosody and Its Functional-Anatomic Organization in Right Hemisphere

    ERIC Educational Resources Information Center

    Ross, Elliott D.; Monnot, Marilee

    2008-01-01

    Unlike the aphasic syndromes, the organization of affective prosody in brain has remained controversial because affective-prosodic deficits may occur after left or right brain damage. However, different patterns of deficits are observed following left and right brain damage that suggest affective prosody is a dominant and lateralized function of…

  1. Non-invasive imaging of flow and vascular function in disease of the aorta

    PubMed Central

    Whitlock, Matthew C.; Hundley, W. Gregory

    2015-01-01

    With advancements in technology and a better understanding of human cardiovascular physiology, research as well as clinical care can go beyond dimensional anatomy offered by traditional imaging and investigate aortic functional properties and the impact disease has on this function. Linking the knowledge of the histopathological changes with the alterations in aortic function observed on noninvasive imaging results in a better understanding of disease pathophysiology. Translating this to clinical medicine, these noninvasive imaging assessments of aortic function are proving to be able to diagnosis disease, better predict risk, and assess response to therapies. This review is designed to summarize the various hemodynamic measures that can characterize the aorta, the various non-invasive techniques, and applications for various disease states. PMID:26381770

  2. Familial Clustering of Executive Functioning in Affected Sibling Pair Families with ADHD

    ERIC Educational Resources Information Center

    Slaats-Willemse, Dorine; Swaab-Barneveld, Hanna; De Sonneville, Leo; Buitelaar, Jan

    2005-01-01

    Objective: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. Method: Fifty-two affected sibling pairs aged 6 to 18 years and diagnosed with ADHD according to DSM-IV performed the…

  3. Vascular ring

    MedlinePlus

    ... with aberrant subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... accounts for less than 1% of all congenital heart problems. The condition occurs as often in males ...

  4. Pulmonary transit of agitated contrast is associated with enhanced pulmonary vascular reserve and right ventricular function during exercise.

    PubMed

    La Gerche, André; MacIsaac, Andrew I; Burns, Andrew T; Mooney, Don J; Inder, Warrick J; Voigt, Jens-Uwe; Heidbüchel, Hein; Prior, David L

    2010-11-01

    Pulmonary transit of agitated contrast (PTAC) occurs to variable extents during exercise. We tested the hypothesis that the onset of PTAC signifies flow through larger-caliber vessels, resulting in improved pulmonary vascular reserve during exercise. Forty athletes and fifteen nonathletes performed maximal exercise with continuous echocardiographic Doppler measures [cardiac output (CO), pulmonary artery systolic pressure (PASP), and myocardial velocities] and invasive blood pressure (BP). Arterial gases and B-type natriuretic peptide (BNP) were measured at baseline and peak exercise. Pulmonary vascular resistance (PVR) was determined as the regression of PASP/CO and was compared according to athletic and PTAC status. At peak exercise, athletes had greater CO (16.0 ± 2.9 vs. 12.4 ± 3.2 l/min, P < 0.001) and higher PASP (60.8 ± 12.6 vs. 47.0 ± 6.5 mmHg, P < 0.001), but PVR was similar to nonathletes (P = 0.71). High PTAC (defined by contrast filling of the left ventricle) occurred in a similar proportion of athletes and nonathletes (18/40 vs. 10/15, P = 0.35) and was associated with higher peak-exercise CO (16.1 ± 3.4 vs. 13.9 ± 2.9 l/min, P = 0.010), lower PASP (52.3 ± 9.8 vs. 62.6 ± 13.7 mmHg, P = 0.003), and 37% lower PVR (P < 0.0001) relative to low PTAC. Right ventricular (RV) myocardial velocities increased more and BNP increased less in high vs. low PTAC subjects. On multivariate analysis, maximal oxygen consumption (VO(2max)) (P = 0.009) and maximal exercise output (P = 0.049) were greater in high PTAC subjects. An exercise-induced decrease in arterial oxygen saturation (98.0 ± 0.4 vs. 96.7 ± 1.4%, P < 0.0001) was not influenced by PTAC status (P = 0.96). Increased PTAC during exercise is a marker of pulmonary vascular reserve reflected by greater flow, reduced PVR, and enhanced RV function.

  5. Optical detection of brain function: simultaneous imaging of cerebral vascular response, tissue metabolism, and cellular activity in vivo.

    PubMed

    Du, Congwu; Pan, Yingtian

    2011-01-01

    It is known that a remaining challenge for functional brain imaging is to distinguish the coupling and decoupling effects among neuronal activity, cerebral metabolism, and vascular hemodynamics, which highlights the need for new tools to enable simultaneous measures of these three properties in vivo. Here, we review current neuroimaging techniques and their prospects and potential limitations for tackling this challenge. We then report a novel dual-wavelength laser speckle imaging (DW-LSI) tool developed in our labs that enables simultaneous imaging of cerebral blood flow (CBF), cerebral blood volume, and tissue hemoglobin oxygenation, which allows us to monitor neurovascular and tissue metabolic activities at high spatiotemporal resolutions over a relatively large field of view. Moreover, we report digital frequency ramping Doppler optical coherence tomography (DFR-OCT) that allows for quantitative 3D imaging of the CBF network in vivo. In parallel, we review calcium imaging techniques to track neuronal activity, including intracellular calcium approach using Rhod2 fluorescence technique that we develop to detect neuronal activity in vivo. We report a new multimodality imaging platform that combines DW-LSI, DFR-OCT, and calcium fluorescence imaging for simultaneous detection of cortical hemodynamics, cerebral metabolism, and neuronal activities of the animal brain in vivo, as well as its integration with microprobes for imaging neuronal function in deep brain regions in vivo. Promising results of in vivo animal brain functional studies suggest the potential of this multimodality approach for future awake animal and behavioral studies.

  6. The functional outcome of lower-extremity fractures with vascular injury.

    PubMed

    Lin, C H; Wei, F C; Levin, L S; Su, J I; Yeh, W L

    1997-09-01

    Salvage of lower-extremity Gustilo type IIIC fractures is difficult, time-consuming for the patients and physicians, and not universally successful because of poor functional outcomes. Even if successful with limb salvage, the functional result may be unsatisfactory because of mutilating injuries to muscle and nerve, bone loss, and the presence of chronic infection. From July 1991 until July 1994, revascularizations of open IIIC fractures were attempted for wounds with Mangled Extremity Severity Score (MESS) < or = 10. The functional results were evaluated at 2 years after injury. Thirty-six lower-extremity revascularizations were performed on 34 patients, including 1 patient with bilateral distal tibial IIIC fractures and a child with IIIC femoral fracture accompanied by ipsilateral distal tibial amputation. Excluded were patients with below-ankle IIIC fractures as well as patients who underwent immediate amputation at admission. After the revascularization, seven patients with IIIC fractures (7 of 36, 19.4%) underwent secondary amputation within 1 week. At the 2-year follow-up, the overall secondary amputation rate was 25% (9 of 36) and the salvage rate was 75% (27 of 36). Those were no deaths. Of the 29 salvaged limbs among these 27 patients, 23 limbs (23 of 29, 79.3%) required secondary coverage procedures that included 12 free flap transfers (12 of 29, 41.4%). Every patient needed subsequent reconstructive surgery to achieve an acceptable functional result. In this series, MESS was able to predict the secondary amputation rate and the functional result. Sixteen of the 17 limb-salvaged patients with MESS < or = 7 were able to achieve minimal functional requirements, whereas 3 of the 10 patients with MESS = 8 to 10 failed to achieve minimal functional requirements at the 2-year follow-up. Using statistical analysis, we found that the salvaged limbs with MESS < or = 9 exhibited a significant difference in achieving adequate function compared with limbs with MESS

  7. Angiotensin II impairs endothelial progenitor cell number and function in vitro and in vivo: implications for vascular regeneration.

    PubMed

    Endtmann, Cathleen; Ebrahimian, Talin; Czech, Thomas; Arfa, Omar; Laufs, Ulrich; Fritz, Mathias; Wassmann, Kerstin; Werner, Nikos; Petoumenos, Vasileios; Nickenig, Georg; Wassmann, Sven

    2011-09-01

    Endothelial progenitor cells (EPCs) contribute to endothelial regeneration. Angiotensin II (Ang II) through Ang II type 1 receptor (AT(1)-R) activation plays an important role in vascular damage. The effect of Ang II on EPCs and the involved molecular mechanisms are incompletely understood. Stimulation with Ang II decreased the number of cultured human early outgrowth EPCs, which express both AT(1)-R and Ang II type 2 receptor, mediated through AT(1)-R activation and induction of oxidative stress. Ang II redox-dependently induced EPC apoptosis through increased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase phosphorylation; decreased Bcl-2 and increased Bax expression; and activation of caspase 3 but had no effect on the low cell proliferation. In addition, Ang II impaired colony-forming and migratory capacities of early outgrowth EPCs. Ang II infusion diminished numbers and functional capacities of EPCs in wild-type (WT) but not AT(1)a-R knockout mice (AT(1)a(-/-)). Reendothelialization after focal carotid endothelial injury was decreased during Ang II infusion. Salvage of reendothelialization by intravenous application of spleen-derived progenitor cells into Ang II-treated WT mice was pronounced with AT(1)a(-/-) cells compared with WT cells, and transfusion of Ang II-pretreated WT cells into WT mice without Ang II infusion was associated with less reendothelialization. Transplantation of AT(1)a(-/-) bone marrow reduced atherosclerosis development in cholesterol-fed apolipoprotein E-deficient mice compared with transplantation of apolipoprotein E-deficient or WT bone marrow. Randomized treatment of patients with stable coronary artery disease with the AT(1)-R blocker telmisartan significantly increased the number of circulating CD34/KDR-positive EPCs. Ang II through AT(1)-R activation, oxidative stress, and redox-sensitive apoptosis signal-regulating kinase 1-dependent proapoptotic pathways impairs EPCs in

  8. Inhibitor-κB kinase attenuates Hsp90-dependent endothelial nitric oxide synthase function in vascular endothelial cells

    PubMed Central

    Konopinski, Ryszard; Krishnan, Manickam; Roman, Linda; Bera, Alakesh; Hongying, Zheng; Habib, Samy L.; Mohan, Sumathy

    2015-01-01

    Endothelial nitric oxide (NO) synthase (eNOS) is the predominant isoform that generates NO in the blood vessels. Many different regulators, including heat shock protein 90 (Hsp90), govern eNOS function. Hsp90-dependent phosphorylation of eNOS is a critical event that determines eNOS activity. In our earlier study we demonstrated an inhibitor-κB kinase-β (IKKβ)-Hsp90 interaction in a high-glucose environment. In the present study we further define the putative binding domain of IKKβ on Hsp90. Interestingly, IKKβ binds to the middle domain of Hsp90, which has been shown to interact with eNOS to stimulate its activity. This new finding suggests a tighter regulation of eNOS activity than was previously assumed. Furthermore, addition of purified recombinant IKKβ to the eNOS-Hsp90 complex reduces the eNOS-Hsp90 interaction and eNOS activity, indicating a competition for Hsp90 between eNOS and IKKβ. The pathophysiological relevance of the IKKβ-Hsp90 interaction has also been demonstrated using in vitro vascular endothelial growth factor-mediated signaling and an Ins2Akita in vivo model. Our study further defines the preferential involvement of α- vs. β-isoforms of Hsp90 in the IKKβ-eNOS-Hsp90 interaction, even though both Hsp90α and Hsp90β stimulate NO production. These studies not only reinforce the significance of maintaining a homeostatic balance of eNOS and IKKβ within the cell system that regulates NO production, but they also confirm that the IKKβ-Hsp90 interaction is favored in a high-glucose environment, leading to impairment of the eNOS-Hsp90 interaction, which contributes to endothelial dysfunction and vascular complications in diabetes. PMID:25652452

  9. Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model

    PubMed Central

    Buchanan, Cara F; Verbridge, Scott S; Vlachos, Pavlos P; Rylander, Marissa Nichole

    2014-01-01

    Endothelial cells lining blood vessels are exposed to various hemodynamic forces associated with blood flow. These include fluid shear, the tangential force derived from the friction of blood flowing across the luminal cell surface, tensile stress due to deformation of the vessel wall by transvascular flow, and normal stress caused by the hydrodynamic pressure differential across the vessel wall. While it is well known that these fluid forces induce changes in endothelial morphology, cytoskeletal remodeling, and altered gene expression, the effect of flow on endothelial organization within the context of the tumor microenvironment is largely unknown. Using a previously established microfluidic tumor vascular model, the objective of this study was to investigate the effect of normal (4 dyn/cm2), low (1 dyn/cm2), and high (10 dyn/cm2) microvascular wall shear stress (WSS) on tumor-endothelial paracrine signaling associated with angiogenesis. It is hypothesized that high WSS will alter the endothelial phenotype such that vascular permeability and tumor-expressed angiogenic factors are reduced. Results demonstrate that endothelial permeability decreases as a function of increasing WSS, while co-culture with tumor cells increases permeability relative to mono-cultures. This response is likely due to shear stress-mediated endothelial cell alignment and tumor-VEGF-induced permeability. In addition, gene expression analysis revealed that high WSS (10 dyn/cm2) significantly down-regulates tumor-expressed MMP9, HIF1, VEGFA, ANG1, and ANG2, all of which are important factors implicated in tumor angiogenesis. This result was not observed in tumor mono-cultures or static conditioned media experiments, suggesting a flow-mediated paracrine signaling mechanism exists with surrounding tumor cells that elicits a change in expression of angiogenic factors. Findings from this work have significant implications regarding low blood velocities commonly seen in the tumor vasculature

  10. Effect of treadmill exercise and Ferula gummosa on myocardial HSP72, vascular function, and antioxidant defenses in spontaneously hypertensive rats.

    PubMed

    Gholitabar, Samira; Roshan, Valiollah Dabidi

    2013-01-01

    This study evaluates the effect of treadmill exercise and Ferula gummosa (FG) on heat shock protein (HSP72), biomarkers related to vascular function, and oxidant/antioxidant system in the heart tissue of spontaneously hypertensive rats treated with N(ω)-nitro-L-arginine-methyl ester (L-NAME). Fifty adult male Wistar rats are randomly classified into five groups: treadmill exercise, FG, combination of treadmill exercise + FG, L-NAME, and saline. Treadmill exercise was performed between 25 and 64 minutes at the speed of 15-22 m per minute for 8 weeks and five sessions a week. The FG will be fed through gavage with 90 mg/kg dosage. Hypertension was induced by l-NAME (10 mg/kg) for 8 weeks and six sessions a week. Administration of L-NAME for 8 weeks caused significant increase in HSP72, angiotensin-converting enzyme (ACE), and protein carbonyl (PC), and significant decrease in glutathione peroxidase (GPx) and nitric oxide (NO) level, when compared with the saline group. In contrast, both treadmill exercise and/or FG protocols, in particular, the combined protocol, led to the improvement in HSP72 and balance in oxidant/antioxidant process and inhibited vascular dysfunction, when compared with the L-NAME group. Moreover, no significant differences were detected in the HSP72 level between rats in the treadmill exercise and FG groups. These results provide a rationale for an inhibitory role and a cardioprotective effect of lifestyle related to the health in the attenuation of hypertension-induced cardiotoxicity.

  11. High fructose-mediated attenuation of insulin receptor signaling does not affect PDGF-induced proliferative signaling in vascular smooth muscle cells.

    PubMed

    Osman, Islam; Poulose, Ninu; Ganapathy, Vadivel; Segar, Lakshman

    2016-11-15

    Insulin resistance is associated with accelerated atherosclerosis. Although high fructose is known to induce insulin resistance, it remains unclear as to how fructose regulates insulin receptor signaling and proliferative phenotype in vascular smooth muscle cells (VSMCs), which play a major role in atherosclerosis. Using human aortic VSMCs, we investigated the effects of high fructose treatment on insulin receptor substrate-1 (IRS-1) serine phosphorylation, insulin versus platelet-derived growth factor (PDGF)-induced phosphorylation of Akt, S6 ribosomal protein, and extracellular signal-regulated kinase (ERK), and cell cycle proteins. In comparison with PDGF (a potent mitogen), neither fructose nor insulin enhanced VSMC proliferation and cyclin D1 expression. d-[(14)C(U)]fructose uptake studies revealed a progressive increase in fructose uptake in a time-dependent manner. Concentration-dependent studies with high fructose (5-25mM) showed marked increases in IRS-1 serine phosphorylation, a key adapter protein in insulin receptor signaling. Accordingly, high fructose treatment led to significant diminutions in insulin-induced phosphorylation of downstream signaling components including Akt and S6. In addition, high fructose significantly diminished insulin-induced ERK phosphorylation. Nevertheless, high fructose did not affect PDGF-induced key proliferative signaling events including phosphorylation of Akt, S6, and ERK and expression of cyclin D1 protein. Together, high fructose dysregulates IRS-1 phosphorylation state and proximal insulin receptor signaling in VSMCs, but does not affect PDGF-induced proliferative signaling. These findings suggest that systemic insulin resistance rather than VSMC-specific dysregulation of insulin receptor signaling by high fructose may play a major role in enhancing atherosclerosis and neointimal hyperplasia.

  12. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

    PubMed Central

    Withers, Sarah B.; Forman, Ruth; Meza-Perez, Selene; Sorobetea, Daniel; Sitnik, Kasia; Hopwood, Thomas; Lawrence, Catherine B.; Agace, William W.; Else, Kathryn J.; Heagerty, Anthony M.; Svensson-Frej, Marcus; Cruickshank, Sheena M.

    2017-01-01

    Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source of these mediators. We conclude that adipose tissue eosinophils play a key role in the regulation of normal PVAT anti-contractile function. PMID:28303919

  13. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease

    PubMed Central

    Lin, Ai-Ling; Zheng, Wei; Halloran, Jonathan J; Burbank, Raquel R; Hussong, Stacy A; Hart, Matthew J; Javors, Martin; Shih, Yen-Yu Ian; Muir, Eric; Solano Fonseca, Rene; Strong, Randy; Richardson, Arlan G; Lechleiter, James D; Fox, Peter T; Galvan, Veronica

    2013-01-01

    Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias. PMID:23801246

  14. Regulation and function of an activation-dependent epitope of the beta 1 integrins in vascular cells after balloon injury in baboon arteries and in vitro.

    PubMed Central

    Koyama, N.; Seki, J.; Vergel, S.; Mattsson, E. J.; Yednock, T.; Kovach, N. L.; Harlan, J. M.; Clowes, A. W.

    1996-01-01

    Migration and proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs) contribute to the response to injury in damaged and atherosclerotic vessels. These events might be regulated by cellular interactions with extracellular matrix through the expression and activation of integrins. To study the functions of beta 1 integrins in the vessel wall, we used monoclonal antibody (MAb) 15/7, which recognizes an activation epitope of beta 1 integrin subunits, and MAb 8A2, which induces a high affinity form of beta 1 integrins recognized by MAb 15/7. Immunohistochemical analyses were done on samples of normal baboon saphenous arteries and from arteries subjected to balloon injury. EC and SMC expressed the activation epitope of beta 1 integrin in uninjured arteries. By contrast, in balloon-injured arteries 6 weeks after injury, regenerating EC did not express the activation epitope, and there was no decrease in the expression of total beta 1 integrin, whereas SMC migrating into the intima exhibited decreased expression of the total and activated beta 1 integrin. Flow cytometer analysis of cultured cells indicated that baboon EC and SMC weakly express the activation epitope of beta 1 integrin. Next, we determined by utilizing MAb 8A2 the effects of increased expression of activation epitope of beta 1 integrin on the functions of SMC and EC. The activation of beta 1 integrins on SMC induced by MAb 8A2 enhanced SMC adhesion and suppressed SMC migration in a Boyden chamber assay. SMC proliferation was inhibited by MAb 8A2 dose-dependently. Similarly, MAb 8A2-induced activation of beta 1 integrins on EC suppressed EC migration into a wound. However, MAb 8A2 did not affect the basic fibroblast growth factor-induced proliferation of EC, although it blocked the decrease in EC number caused by the removal of basic fibroblast growth factor. These results suggest that activation of beta 1 integrins in vascular cells is regulated in a cell-type dependent manner and plays an

  15. Correlation of CT cerebral vascular territories with function. 3. Middle cerebral artery

    SciTech Connect

    Berman, S.A.; Hayman, L.A.; Hinck, V.C.

    1984-05-01

    Schematic displays are presented of the cerebral territories supplied by branches of the middle cerebral artery as they would appear on axial and coronal computed tomographic (CT) scan sections. Companion diagrams of regional cortical function and a discussion of the fiber tracts are provided to simplify correlation of clinical deficits with coronal and axial CT abnormalities.

  16. Role of leptin signaling in hemato-vascular development and niche function: Leptin receptor-mediated signaling regulates LT-HSC homeostasis in vivo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Homeostatic functioning of the cardiovascular and hematopoietic systems is known to be interdependent and strongly influenced by the microenvironment in which hemato-vascular cells develop and reside. The role of nutrition and metabolism as regulable and dynamic extracellular cues however, remains a...

  17. EFFECT OF OIL COMBUSTION PARTICLE BIOAVAILABLE CONSTITUENTS ON EX VIVO VASCULAR FUNCTION OF AORTAS RECOVERED FROM NORMAL AND TYPE 2 DIABETIC RATS

    EPA Science Inventory

    Effect of Oil Combustion Particle Bioavailable Constituents on Ex Vivo Vascular Function of Aortae Recovered from Healthy and Early Type 2 Diabetic Rats
    KL Dreher1, SE Kelly2, SD Proctor2, and JC Russell2. 1National Health and Environmental Effects Laboratory, US EPA, RTP, NC;...

  18. Improved functional status by comprehensive physical and psychosocial approach through right insula activation in poststroke vascular dementia.

    PubMed

    Tanaka, Naofumi; Meguro, Kenichi; Ishikawa, Hiroyasu; Yamaguchi, Satoshi

    2013-10-01

    The aim is to investigate the effect of a comprehensive physical and psychosocial approach on functional outcome and cerebral glucose metabolism in poststroke vascular dementia (PSVaD). Ten PSVaD patients participated in the study. They were diagnosed according to the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN) criteria and needed physical assistance in sit-to-stand transfer activities. Six were enrolled in a comprehensive program consisted of an individualized task-specific exercise regimen of transfer training and a psychosocial intervention program. The other 4 patients participated in the control group. The programs were undertaken over a period of 2 months. Outcomes were the scores on the Mini-Mental State Examination and the Functional Independence Measure (FIM), and on cerebral glucose metabolism determined by (18)F-fluorodeoxyglucose positron emission tomography performed before and at the end of the program. The score on the transfer mobility subscale of the FIM increased at the end of the program in all patients who received the comprehensive program. Regional glucose metabolism was increased in the right insular cortex at the end of the combined program. Control patients showed no change in FIM score or regional cerebral metabolism. A combined approach may be associated with an increase in glucose metabolism of the right insula cortex in PSVaD patients.

  19. Increasing functional modularity with residence time in the co-distribution of native and introduced vascular plants

    PubMed Central

    Hui, Cang; Richardson, David M.; Pyšek, Petr; Le Roux, Johannes J.; Kučera, Tomáš; Jarošík, Vojtěch

    2013-01-01

    Species gain membership of regional assemblages by passing through multiple ecological and environmental filters. To capture the potential trajectory of structural changes in regional meta-communities driven by biological invasions, one can categorize species pools into assemblages of different residence times. Older assemblages, having passed through more environmental filters, should become more functionally ordered and structured. Here we calculate the level of compartmentalization (modularity) for three different-aged assemblages (neophytes, introduced after 1500 AD; archaeophytes, introduced before 1500 AD, and natives), including 2,054 species of vascular plants in 302 reserves in central Europe. Older assemblages are more compartmentalized than younger ones, with species composition, phylogenetic structure and habitat characteristics of the modules becoming increasingly distinctive. This sheds light on two mechanisms of how alien species are functionally incorporated into regional species pools: the settling-down hypothesis of diminishing stochasticity with residence time, and the niche-mosaic hypothesis of inlaid neutral modules in regional meta-communities. PMID:24045305

  20. Phylogeny, topology, structure and functions of membrane-bound class III peroxidases in vascular plants.

    PubMed

    Lüthje, Sabine; Meisrimler, Claudia-Nicole; Hopff, David; Möller, Benjamin

    2011-07-01

    Peroxidases are key player in the detoxification of reactive oxygen species during cellular metabolism and oxidative stress. Membrane-bound isoenzymes have been described for peroxidase superfamilies in plants and animals. Recent studies demonstrated a location of peroxidases of the secretory pathway (class III peroxidases) at the tonoplast and the plasma membrane. Proteomic approaches using highly enriched plasma membrane preparations suggest organisation of these peroxidases in microdomains, a developmentally regulation and an induction of isoenzymes by oxidative stress. Phylogenetic relations, topology, putative structures, and physiological function of membrane-bound class III peroxidases will be discussed.

  1. Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease.

    PubMed

    Zizioli, Daniela; Tiso, Natascia; Guglielmi, Adele; Saraceno, Claudia; Busolin, Giorgia; Giuliani, Roberta; Khatri, Deepak; Monti, Eugenio; Borsani, Giuseppe; Argenton, Francesco; Finazzi, Dario

    2016-01-01

    Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this

  2. Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease

    PubMed Central

    Zizioli, Daniela; Tiso, Natascia; Guglielmi, Adele; Saraceno, Claudia; Busolin, Giorgia; Giuliani, Roberta; Khatri, Deepak; Monti, Eugenio; Borsani, Giuseppe; Argenton, Francesco; Finazzi, Dario

    2016-01-01

    Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this

  3. Choline inadequacy impairs trophoblast function and vascularization in cultured human placental trophoblasts.

    PubMed

    Jiang, Xinyin; Jones, Sara; Andrew, Benjamin Y; Ganti, Anita; Malysheva, Olga V; Giallourou, Natasa; Brannon, Patsy M; Roberson, Mark S; Caudill, Marie A

    2014-08-01

    Maternal choline intake during gestation may influence placental function and fetal health outcomes. Specifically, we previously showed that supplemental choline reduced placental and maternal circulating concentrations of the anti-angiogenic factor, fms-like tyrosine kinase-1 (sFLT1), in pregnant women as well as sFLT1 production in cultured human trophoblasts. The current study aimed to quantify the effect of choline on a wider array of biomarkers related to trophoblast function and to elucidate possible mechanisms. Immortalized HTR-8/SVneo trophoblasts were cultured in different choline concentrations (8, 13, and 28 µM [control]) for 96-h and markers of angiogenesis, inflammation, apoptosis, and blood vessel formation were examined. Choline insufficiency altered the angiogenic profile, impaired in vitro angiogenesis, increased inflammation, induced apoptosis, increased oxidative stress, and yielded greater levels of protein kinase C (PKC) isoforms δ and ϵ possibly through increases in the PKC activators 1-stearoyl-2-arachidonoyl-sn-glycerol and 1-stearoyl-2-docosahexaenoyl-sn-glycerol. Notably, the addition of a PKC inhibitor normalized angiogenesis and apoptosis, and partially rescued the aberrant gene expression profile. Together these results suggest that choline inadequacy may contribute to placental dysfunction and the development of disorders related to placental insufficiency by activating PKC.

  4. Functional proteomics reveal the effect of Salvia miltiorrhiza aqueous extract against vascular atherosclerotic lesions.

    PubMed

    Hung, Yu-Chiang; Wang, Pei-Wen; Pan, Tai-Long

    2010-06-01

    Salvia miltiorrhiza is a Chinese herb widely used for cardiovascular disorder regimens, yet little is known about the cellular mechanisms that contribute to attenuated growth of smooth muscle cells (SMCs) under oxidative stress such as homocysteine (Hcy) treatment. As anticipated, a low dose (0.015 mg/mL) of S.miltiorrhiza aqueous extract (SMAE) significantly inhibited (>60%) the growth of a rat smooth muscle cell line (A10) under Hcy stimulation and the intracellular reactive oxygen species (ROS) concentration obviously decreased after SMAE treatment in terms of reducing p47(phox) translocation and increasing catalase activity. Signaling profile suggests that SMAE inhibited Hcy-induced A10 cell growth via the PKC/MAPK-dependent pathway. Two-dimensional electrophoresis (2-DE) coupled with mass spectrometry revealed statistically significant changes in the intensity of 14 proteins in response to Hcy and Hcy/SMAE. Meanwhile, SMAE attenuated carbonyl-modification of specific cytoskeleton and chaperone proteins leading to cell type transformation. Moreover, a network analysis using MetaCore shed more light on the molecular basis associated with SMAE efficacy. SMAE exerts its protective effect through the scavenging of ROS and subsequent modulation of protein carbonylation to inhibit cell proliferation. These signature networks and functional proteomics highlighted herein may facilitate the evaluation of potential therapeutic targets and elucidate novel mechanisms through which protein functions can be regulated by the redox status.

  5. Nitric oxide-mediated vascular function in sepsis using passive leg movement as a novel assessment: a cross-sectional study.

    PubMed

    Nelson, Ashley D; Rossman, Matthew J; Witman, Melissa A; Barrett-O'Keefe, Zachary; Groot, H Jonathan; Garten, Ryan S; Richardson, Russell S

    2016-05-01

    Post-cuff occlusion flow-mediated dilation (FMD) is a proposed indicator of nitric oxide (NO) bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates poor reproducibility. In contrast, passive leg movement (PLM), a novel methodology to assess vascular function, yields a hyperemic response that is predominately NO-dependent, reproducible, and easily measured. This study evaluated PLM as an approach to assess NO-mediated vascular function in patients with sepsis. We hypothesized that PLM-induced hyperemia, quantified by the increase in leg blood flow (LBF), would be attenuated in sepsis. In a cross-sectional study, 17 subjects in severe sepsis or septic shock were compared with 16 matched healthy controls. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response to PLM in the femoral artery. FMD was attenuated in septic compared with control subjects (1.1 ± 1.7% vs. 6.8 ± 1.3%; values are means ± SD). In terms of PLM, baseline LBF (196 ± 33 ml/min vs. 328 ± 20 ml/min), peak change in LBF from baseline (133 ± 28 ml/min vs. 483 ± 86 ml/min), and the LBF area under the curve (16 ± 8.3 vs. 143 ± 33) were all significantly attenuated in septic subjects. Vascular function, as assessed by both FMD and PLM, is attenuated in septic subjects compared with controls. These data support the concept that NO bioavailability is attenuated in septic subjects, and PLM appears to be a novel and feasible approach to assess NO-mediated vascular function in sepsis.

  6. Age related vascular endothelial function following lifelong sedentariness: positive impact of cardiovascular conditioning without further improvement following low frequency high intensity interval training

    PubMed Central

    Grace, Fergal M.; Herbert, Peter; Ratcliffe, John W.; New, Karl J.; Baker, Julien S.; Sculthorpe, Nicholas F.

    2015-01-01

    Abstract Aging is associated with diffuse impairments in vascular endothelial function and traditional aerobic exercise is known to ameliorate these changes. High intensity interval training (HIIT) is effective at improving vascular function in aging men with existing disease, but its effectiveness remains to be demonstrated in otherwise healthy sedentary aging. However, the frequency of commonly used HIIT protocols may be poorly tolerated in older cohorts. Therefore, the present study investigated the effectiveness of lower frequency HIIT (LfHIIT) on vascular function in a cohort of lifelong sedentary (SED; n =22, age 62.7 ± 5.2 years) men compared with a positive control group of lifelong exercisers (LEX; n = 17, age 61.1 ± 5.4 years). The study consisted of three assessment phases; enrolment to the study (Phase A), following 6 weeks of conditioning exercise in SED (Phase B) and following 6 weeks of low frequency HIIT in both SED and LEX (LfHIIT; Phase C). Conditioning exercise improved FMD in SED (3.4 ± 1.5% to 4.9 ± 1.1%; P <0.01) such that the difference between groups on enrolment (3.4 ± 1.5% vs. 5.3 ± 1.4%; P <0.01) was abrogated. This was maintained but not further improved following LfHIIT in SED whilst FMD remained unaffected by LfHIIT in LEX. In conclusion, LfHIIT is effective at maintaining improvements in vascular function achieved during conditioning exercise in SED. LfHIIT is a well‐tolerated and effective exercise mode for reducing cardiovascular risk and maintaining but does not improve vascular function beyond that achieved by conditioning exercise in aging men, irrespective of fitness level. PMID:25626864

  7. Predicting the accuracy of facial affect recognition: the interaction of child maltreatment and intellectual functioning.

    PubMed

    Shenk, Chad E; Putnam, Frank W; Noll, Jennie G

    2013-02-01

    Previous research demonstrates that both child maltreatment and intellectual performance contribute uniquely to the accurate identification of facial affect by children and adolescents. The purpose of this study was to extend this research by examining whether child maltreatment affects the accuracy of facial recognition differently at varying levels of intellectual functioning. A sample of maltreated (n=50) and nonmaltreated (n=56) adolescent females, 14 to 19 years of age, was recruited to participate in this study. Participants completed demographic and study-related questionnaires and interviews to control for potential psychological and psychiatric confounds such as symptoms of posttraumatic stress disorder, negative affect, and difficulties in emotion regulation. Participants also completed an experimental paradigm that recorded responses to facial affect displays starting in a neutral expression and changing into a full expression of one of six emotions: happiness, sadness, anger, disgust, fear, or surprise. Hierarchical multiple regression assessed the incremental advantage of evaluating the interaction between child maltreatment and intellectual functioning. Results indicated that the interaction term accounted for a significant amount of additional variance in the accurate identification of facial affect after controlling for relevant covariates and main effects. Specifically, maltreated females with lower levels of intellectual functioning were least accurate in identifying facial affect displays, whereas those with higher levels of intellectual functioning performed as well as nonmaltreated females. These results suggest that maltreatment and intellectual functioning interact to predict the recognition of facial affect, with potential long-term consequences for the interpersonal functioning of maltreated females.

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

    PubMed Central

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

    2015-01-01

    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

  9. The impact of milk proteins and peptides on blood pressure and vascular function: a review of evidence from human intervention studies.

    PubMed

    Fekete, Ágnes A; Givens, D Ian; Lovegrove, Julie A

    2013-12-01

    CVD are the leading cause of death worldwide. Hypertension, a major controllable risk factor of CVD, is intimately associated with vascular dysfunction, a defect which is also now recognised to be a major, modifiable risk factor for the development of CVD. The purpose of the present review was to critically evaluate the evidence for the effects of milk proteins and their associated peptides on blood pressure (BP) and vascular dysfunction. After a detailed literature search, the number of human trials evaluating the antihypertensive effects of casein-derived peptides (excluding isoleucine-proline-proline and valine-proline-proline) was found to be limited; the studies were preliminary with substantial methodological limitations. Likewise, the data from human trials that examined the effects of whey protein and peptides were also scarce and inconsistent. To date, only one study has conducted a comparative investigation on the relative effects of the two main intact milk proteins on BP and vascular function. While both milk proteins were shown to reduce BP, only whey protein improved measures of arterial stiffness. In contrast, a growing number of human trials have produced evidence to support beneficial effects of both milk proteins and peptides on vascular health. However, comparison of the relative outcomes from these trials is difficult owing to variation in the forms of assessment and measures of vascular function. In conclusion, there is an accumulating