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Endothelium
Kinds of Endothelium Selected AbstractsContribution of endothelium-derived hyperpolarizing factors to the regulation of vascular tone in humansFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2008Jeremy Bellien Abstract Endothelium plays a crucial role in the regulation of cardiovascular homeostasis through the release of vasoactive factors. Besides nitric oxide (NO) and prostacyclin, increasing evidences show that endothelium-derived hyperpolarizing factors (EDHF) participate in the control of vasomotor tone through the activation of calcium-activated potassium channels. In humans, the role of EDHF has been demonstrated in various vascular beds including coronary, peripheral, skin and venous vessels. The mechanisms of EDHF-type relaxations identified in humans involved the release by the endothelium of hydrogen peroxide, epoxyeicosatrienoic acids (EETs), potassium ions and electronical communication through the gap junctions. The role of EETs could be particularly important because, in addition contributing to the maintenance of the basal tone and endothelium-dependent dilation of conduit arteries, these factors share many vascular protective properties of NO. The alteration of which might be involved in the physiopathology of cardiovascular diseases. The evolution of EDHF availability in human pathology is currently under investigation with some results demonstrating an increase in EDHF release to compensate the loss of NO synthesis and to maintain the endothelial vasomotor function whereas others reported a parallel decrease in NO and EDHF-mediated relaxations. Thus, the modulation of EDHF activity emerges as a new pharmacological target and some existing therapies in particular those affecting the renin,angiotensin system have already been shown to improve endothelial function through hyperpolarizing mechanisms. In this context, the development of new specific pharmacological agents especially those increasing EETs availability may help to prevent endothelial dysfunction and therefore enhance cardiovascular protection in patients. [source] Interactions of Platelets with Subendothelium and EndotheliumMICROCIRCULATION, Issue 3 2005JUNMEI CHEN PhD ABSTRACT In this review, the authors summarize how platelets interact with subendothelium when the vessel wall is damaged or with intact endothelium in the inflammatory state. When subendothelium is exposed to rapidly flowing blood upon vessel damage, platelets adhere rapidly to the exposed surface, decelerate, and aggregate to arrest bleeding. Under high shear stress, such as is found in the microcirculation, the interaction between subendothelial von Willebrand factor (VWF) and its platelet receptor, glycoprotein (GP) Ib-IX-V, is required to slow down platelets and allow the platelet collagen receptors ,2,1 and GP VI to bind to collagen. GP VI and ,2,1 play important roles to activate platelets in the early stage and work with GP Ib-IX-V to fully activate platelets to form thrombi. GP Ib-IX-V and GP VI employ similar signaling pathways for platelet activation and the signals from both receptors are down-modulated by PECAM-1 (platelet,endothelial,cell adhesion molecule 1) to prevent unnecessary platelet activation under high shear. During inflammatory states, intact endothelial cells release VWF and P-selectin from their Weibel-Palade bodies. Both molecules are ligands for GP Ib-IX-V. The newly released VWF is larger and stickier than the form normally found in plasma and binds platelets spontaneously. Normally, VWF is processed by proteolysis by the plasma metalloprotease ADAMTS-13. Failure of this processing results in the microvascular thrombotic disorder thrombotic thrombocytopenic purpura. In this review, the authors also use available crystal structures of platelet receptors and ligands to explain the details of their interactions. [source] Effects of Arg-Gly-Asp Sequence Peptide and Hyperosmolarity on the Permeability of Interstitial Matrix and Fenestrated Endothelium in JointsMICROCIRCULATION, Issue 6 2004A. POLI ABSTRACT Objectives: The aims were to assess the contribution of arg-gly-asp (RGD) mediated cell integrin,matrix bonds to interstitial hydraulic resistance and to fenestrated endothelial permeability in joints. Joint fluid is generated by filtration from fenestrated capillaries and drains through a fibronectin-rich synovial intercellular matrix. The role of parenchymal cell,matrix bonding in determining tissue hydraulic resistance is unknown. Methods: The knee cavity of anesthetized rabbits was infused with saline or the competitive hexapeptide blocker GRGDTP, with or without added osmotic stress (600 mosm saline). Intra-articular pressure Pj, net trans-synovial drainage rate s, and the permeation of Evans blue-labeled albumin (EVA) from plasma into the joint cavity were measured. Results: GRGDTP increased the hydraulic conductance of the synovial drainage pathway, ds/dPj, by 71% (p = .02, paired t test, n = 6 animals). Synovial plasma EVA clearance (control 7.1 ± 0.8 ,L h,1, mean ± SEM, n = 15) was unaffected by GRGDTP (7.0 ± 2.3 ,L h,1, n = 6) or hyperosmolarity (4.9 ± 1.5 ,L h,1, n = 8) but was increased by GRGDTP and hyperosmolarity together (15.9 ± 4.8 ,L h,1, n = 5) (p = .01, ANOVA). Changes in dPj/dt evoked by GRGDTP plus hyperosmolarity, but neither alone, demonstrated increased microvascular filtration into the joint cavity (p < .001, ANOVA), as did changes in fluid absorption from the infusion system at fixed Pj. Conclusions: RGD-mediated bonds between the parenchymal cells and interstitial polymers reduce the interstitial hydraulic conductance by 42%. This helps to retain the lubricating fluid inside a joint cavity. RGD-mediated bonds also support the macromolecular barrier function of fenestrated endothelium, but in vivo this is evident only in stressed endothelium (cf. in vitro). [source] LIPID-LOWERING IMPROVES ENDOTHELIAL FUNCTION IN NEPHROTIC RANGE PROTEINURIANEPHROLOGY, Issue 3 2000G. Dogra OBJECTIVE: To determine whether lipid-modifying therapy with atorvastatin improves impaired endothelial function in patients with nephrotic range proteinuria (NRP). METHODS: A sequential, open-label study of the effects of atorvastatin on dyslipidaemia and endothelial dysfunction in 9 patients with NRP. Endothelial function was assessed at baseline, after 12 weeks of atorvastatin treatment and after an 8 week wash-out period. Brachial artery endothelial function was studied by measuring post-ischaemic flow-mediated dilatation (FMD) using ultrasonography. Endothelium- independent, glyceryl trinitrate (GTN) mediated vasodilatation was also measured. RESULTS: At baseline, median serum albumin was 31g/L (range 20-40) and 24 hour protein excretion was 4.7g (1.0-16.23). There was no significant change in serum creatinine and 24 hour protein excretion during the study. Total cholesterol (TC) and triglycerides (TG) were significantly lower following treatment with atorvastatin 20mg (20-40): TC 8.1mmol/L (5.9-14.9) vs. 5.2 (4.0-8.6), TG 2.9mmol/L (1.3-15.0) vs. 1.6 (1.0-3.5), both p < 0.05. Brachial artery FMD improved significantly following atorvastatin treatment: 2.1% (-1.2- 5.2%) to 4.7% (0.8-16.3%), p < 0.05. At the end of the 8 week wash-out, FMD had significantly deteriorated to 3.2% (-2.8-8.2), p < 0.05 vs. week 12 FMD, and was similar to pre-treatment values. GTN mediated dilatation was unchanged through the study. CONCLUSION: Atorvastatin significantly reduced the hyperlipidaemia of NRP. This was associated with improved conduit artery endothelial function after 12 weeks of treatment. This is consistent with the hypothesis that dyslipoproteinaemia is the primary cause of endothelial dysfunction in NRP. [source] Effect of Antibodies on EndotheliumAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009X. Zhang Patients developing posttransplant antibodies against HLA and non-HLA antigens expressed by the endothelium of the graft undergo more frequent episodes of rejection and have decreased long-term graft survival. Antibodies against the endothelium can alter/damage the cells of the graft through several mechanisms. Historically, antibodies were thought to elicit endothelial cell injury via complement-dependent mechanisms. New research has shown that antibodies can also contribute to the process of transplant rejection by stimulating proinflammatory and proproliferation signals. Antibody ligation leads to several functional alterations in EC including Weibel Palade body exocytosis, leukocyte recruitment, growth factor expression and cell proliferation. In contrast, under certain circumstances, antibodies may induce prosurvival signals and graft accommodation. The signaling events regulating accommodation vs. rejection appear to be influenced by the specificity and concentration of the anti-HLA antibody and the degree of molecular aggregation. Knowledge of the HLA and non-HLA antibody-mediated signaling pathways has the potential to identify new therapeutic targets to promote accommodation and prevent acute and chronic antibody-mediated rejection. [source] Corneal Graft Rejection Is Accompanied by Apoptosis of the Endothelium and Is Prevented by Gene Therapy With Bcl-xLAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2007R. N Barcia Corneal transplants normally enjoy a high percentage of survival, mainly because the eye is an immune-privileged site. When allograft failure occurs, it is most commonly due to rejection, an immune-mediated reaction that targets the corneal endothelium. While the exact mechanism by which the endothelium is targeted is still unknown, we postulate that corneal endothelial cell loss during allograft failure is mediated by apoptosis. Furthermore, because corneal endothelial cells do not normally regenerate, we hypothesize that suppressing apoptosis in the graft endothelium will promote transplant survival. In a murine model of transplantation, TUNEL staining and confocal microscopy showed apoptosis of the graft endothelium occurring in rejecting corneas as early as 2 weeks posttransplantation. We found that bcl-xL protected cultured corneal endothelial cells from apoptosis and that lentiviral delivery of bcl-xL to the corneal endothelium of donor corneas significantly improved the survival of allografts. These studies suggest a novel approach to improve corneal allograft survival by preventing apoptosis of the endothelium. [source] Antiangiogenic and Immunomodulatory Effects of Rapamycin on Islet Endothelium: Relevance for Islet TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2006V. Cantaluppi Donor intra-islet endothelial cells contribute to neovascularization after transplantation. Several factors may interfere with this process and ultimately influence islet engraftment. Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. The aim of this study was to evaluate the effects of rapamycin on islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from freshly purified human islets and the formation of capillary-like structures in vitro and in vivo after subcutaneous injection within Matrigel plugs into SCID mice. Rapamycin decreased migration, proliferation and angiogenic properties of human and mouse islet-derived endothelial cell lines with appearance of apoptosis. The expression of angionesis-related factors VEGF, ,V,3 integrin and thrombospondin-1 on islet endothelium was altered in the presence of rapamycin. On the other hand, rapamycin decreased the surface expression of molecules involved in immune processes such as ICAM-1 and CD40 and reduced the adhesion of T cells to islet endothelium. Our results suggest that rapamycin exerts dual effects on islet endothelium inducing a simultaneous inhibition of angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion and activation. [source] Ozonated Autohemotherapy in Patients on Maintenance Hemodialysis: Influence on Lipid Profile and EndotheliumARTIFICIAL ORGANS, Issue 2 2004Leszek Tylicki Abstract:, Ozonated autohemotherapy (O3-AHT) is used in the treatment of atherosclerotic ischemia of lower limbs (AILL). The impact of ozone on serum lipids and endothelium injury is of particular interest since these factors are important in the development of atherosclerotic lesions. To evaluate this issue, a prospective, placebo-controlled study was designed. Twelve hemodialyzed subjects with AILL received autohemotherapy with oxygen as a control followed by O3-AHT with ozone concentration of 50 µg/ml. Serum lipids and plasma activity of von Willebrand factor (vWF) were measured. After O3-AHT, total cholesterol significantly decreased compared to the baseline (,8.34%) [P < 0.01]. LDL cholesterol was also significantly lower than the initial value (,17.71%) [P < 0.001]. No significant changes in the activity of vWF were found after the first session of O3-AHT and after all nine sessions of O3-AHT. The study demonstrated that O3-AHT did not affect deleteriously the endothelium in patients with chronic renal failure on maintenance hemodialysis. It ,may stimulate beneficial changes in serum lipid profile manifesting as,,a, decrease ,in the total- and LDL-cholesterol ,levels. [source] Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats,HEPATOLOGY, Issue 4 2007Mercedes Fernandez Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) pathways are crucial to angiogenesis, a process that contributes significantly to the pathogenesis of portal hypertension. This study determined the effects of inhibition of VEGF and/or PDGF signaling on hyperdynamic splanchnic circulation and portosystemic collateralization in rats with completely established portal hypertension, thus mimicking the situation in patients. Portal vein,ligated rats were treated with rapamycin (VEGF signaling inhibitor), Gleevec (PDGF signaling inhibitor), or both simultaneously when portal hypertension was already fully developed. Hemodynamic studies were performed by transit-time flowmetry. The extent of portosystemic collaterals was measured by radioactive microspheres. The expression of angiogenesis mediators was determined by Western blotting and immunohistochemistry. Combined inhibition of VEGF and PDGF signaling significantly reduced splanchnic neovascularization (i.e., CD31 and VEGFR-2 expression) and pericyte coverage of neovessels (that is, ,-smooth muscle actin and PDGFR-, expression) and translated into hemodynamic effects as marked as a 40% decrease in portal pressure, a 30% decrease in superior mesenteric artery blood flow, and a 63% increase in superior mesenteric artery resistance, yielding a significant reversal of the hemodynamic changes provoked by portal hypertension in rats. Portosystemic collateralization was reduced as well. Conclusions: Our results provide new insights into how angiogenesis regulates portal hypertension by demonstrating that the maintenance of increased portal pressure, hyperkinetic circulation, splanchnic neovascularization, and portosystemic collateralization is regulated by VEGF and PDGF in portal hypertensive rats. Importantly, these findings also suggest that an extended antiangiogenic strategy (that is, targeting VEGF/endothelium and PDGF/pericytes) may be a novel approach to the treatment of portal hypertension. (HEPATOLOGY 2007.) [source] Vascular endothelial growth factor in edematous mouse embryos induced by retinoic acid in uteroCONGENITAL ANOMALIES, Issue 2 2001Yoshiko Yasuda ABSTRACT, Vascular endothelial growth factor (VEGF) is induced by hypoxic environment and contributes to vascular formation in both developing embryos and adults. Exogenous retinoic acid (RA) induces avascular yolk sacs with anemic stunted embryos of day 9 and 10 of gestation when RA is given to pregnant mice on day 6, 6.5 or 7 of pregnancy (Yasuda et al., 1996). We undertook the present studies to find out whether VEGF is activated and plays any role in those RA-exposed embryos. Embryos were obtained from dams given 60 mg/kg of RA on day 6 or 7 of pregnancy and sacrificed three days later. Most RA-exposed embryos showed edematous swelling without prominent vascular nets, but had beating heart tubes on day 9 and day 10 of gestation. Microscopic examination of developing tissue components showed various degrees of degeneration, and distension of the dorsal aorta when the body cavity was dosed. Northern blot analysis revealed expression of VEGF mRNA in the RA-exposed and control embryos. The highest expression of VEGF mRNA was seen in the embryos of day 10 exposed to RA on day 7, and these embryos had a significantly lower ATP content than did the controls (p < 0.01). Immunoreactive VEGF was detectable in both experimental and control embryos; in the former it was especially visible in the distended neuroepithelium, endothelium and membranes. These VEGF-immunoreactive regions also expressed another permeability factor, bradykinin. These findings suggest that VEGF upregulated by hypoxic conditions in edematous embryos induced by RA exposure in utero acts as hyperpermeability. [source] The effects of acute and chronic exercise on the vasculatureACTA PHYSIOLOGICA, Issue 4 2010J. J. Whyte Abstract Regular physical activity (endurance training, ET) has a strong positive link with cardiovascular health. The aim of this review is to draw together the current knowledge on gene expression in different cell types comprising the vessels of the circulatory system, with special emphasis on the endothelium, and how these gene products interact to influence vascular health. The effect beneficial effects of ET on the endothelium are believed to result from increased vascular shear stress during ET bouts. A number of mechanosensory mechanisms have been elucidated that may contribute to the effects of ET on vascular function, but there are questions regarding interactions among molecular pathways. For instance, increases in flow brought on by ET can reduce circulating levels of viscosity and haemostatic and inflammatory variables that may interact with increased shear stress, releasing vasoactive substances such as nitric oxide and prostacyclin, decreasing permeability to plasma lipoproteins as well as the adhesion of leucocytes. At this time the optimal rate-of-flow and rate-of-change in flow for determining whether anti-atherogenic or pro-atherogenic processes proceed remain unknown. In addition, the impact of haemodynamic variables differs with vessel size and tissue type in which arteries are located. While the hurdles to understanding the mechanism responsible for ET-induced alterations in vascular cell gene expression are significant, they in no way undermine the established benefits of regular physical activity to the cardiovascular system and to general overall health. This review summarizes current understanding of control of vascular cell gene expression by exercise and how these processes lead to improved cardiovascular health. [source] Potential Role of Type 5 Phosphodiesterase Inhibition in the Treatment of Congestive Heart FailureCONGESTIVE HEART FAILURE, Issue 1 2003Stuart D. Katz MD Endothelial dysfunction is associated with impairment of aerobic capacity in patients with heart failure and may play a role in the progression of disease. Impaired endothelium-dependent vasodilation in patients with heart failure can be attributed to decreased bioavailability of nitric oxide and attenuated responses to nitric oxide in vascular smooth muscle. Impaired vasodilation in response to nitric oxide derived from vascular endothelium or organic nitrates in vascular smooth muscle may be related in part to increased degradation of the second messenger cyclic guanosine monophosphate by type 5 phosphodiesterase. Sildenafil, a specific type 5 phosphodiesterase inhibitor currently approved for the treatment of erectile dysfunction, has been shown to acutely enhance endothelium-dependent vasodilation in patients with heart failure. Further studies are warranted to characterize the safety and efficacy of type 5 phosphodiesterase inhibition in the treatment of chronic heart failure. [source] Role of shear stress on nitrite and NOS protein content in different size conduit arteries of swineACTA PHYSIOLOGICA, Issue 2 2009X. Guo Abstract Aim:, Inherent fundamental difference exists among arteries of different sizes. The purpose of this study was to evaluate the relation between regional difference of wall shear stress (WSS) in various sizes arteries and contents of nitrite and NO synthase (NOS) isoforms. Methods:, Five different conduit arteries in a wide range of diameter (1,8 mm) were examined in the hind limbs of 13 pigs. Blood flow rate and outer diameter were measured in vivo to determine WSS. Arterial tissues were harvested for the measurement of nitrite and NOS protein contents. The concentration of nitrite, a product of NO synthesis, was determined by high-performance liquid chromatography method. Western blot analysis was used to assess the protein contents of endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS). Results:, Our data show that WSS increases with a decrease in artery diameter. Nitrite level increases with increasing WSS and hence decreases with artery diameter. The eNOS protein contents decrease with an increase in diameter. No significant difference for iNOS and nNOS protein contents was found with different artery diameter. A significant positive correlation between tissue nitrite and eNOS protein contents was also observed. Finally, the WSS-normalized eNOS is not significantly different in various size vessels. Conclusion:, Regional difference in blood flow has no effect on iNOS and nNOS protein contents in these conduit arteries. Regional difference in eNOS expression and nitrite contents may be related to the WSS-induced NO by the endothelium under normal physiological conditions. [source] Similarity of permeabilities for Ficoll, pullulan, charge-modified albumin and native albumin across the rat peritoneal membraneACTA PHYSIOLOGICA, Issue 4 2009D. Asgeirsson Abstract Aim:, Compared to neutral globular proteins, neutral polysaccharides, such as dextran, pullulan and Ficoll, appear hyperpermeable across the glomerular filtration barrier. This has been attributed to an increased flexibility and/or asymmetry of polysaccharides. The present study investigates whether polysaccharides are hyperpermeable also across the continuous capillaries in the rat peritoneum. Methods:, In anaesthetized Wistar rats, FITC,Ficoll or FITC,pullulan together with 125I-human serum albumin (RISA) or neutralized 125I-bovine serum albumin (nBSA) were given intravenously, after which peritoneal dialysis (PD) using conventional PD fluid (Gambrosol 1.5%) was performed for 120 min. Concentrations of FITC-polysaccharides and radioactive albumin species in plasma and dialysis fluid were analysed with high-performance size exclusion chromatography and a gamma counter respectively. Transperitoneal clearance values were calculated for polysaccharides in the molecular radius range 36,150 Å, and for RISA and nBSA. Results:, Ficoll and pullulan showed more or less identical permeabilities, compared to RISA and nBSA, across the peritoneal membrane. Although RISA-clearance, 5.50 ± 0.28 (,L min,1; ±SEM), tended to be lower than the clearances of Ficoll36Å (6.55 ± 0.25), pullulan36Å (6.08 ± 0.22) and nBSA (6.56 ± 0.23), the difference was not statistically significant. This is in contrast to the hyperpermeability exhibited by polysaccharides across the glomerular filtration barrier and also contrasts with the charge selectivity of the latter. Conclusion:, The phenomenon of molecular flexibility is more important for a macromolecule's permeability through the glomerular filter than across the continuous peritoneal capillary endothelium. Furthermore, it seems that charge plays a subordinate role in the steady-state transport across the combined peritoneal capillary,interstitial barrier. [source] Effects of normobaric hyperoxia on water content in different organs in ratsACTA PHYSIOLOGICA, Issue 1 2002L. E. B. Stuhr ABSTRACT Pulmonary oxygen toxicity is a dose-dependent effect on alveolar epithelial and endothelial cells resulting in pulmonary oedema. Any concomitant effects on systemic capillary endothelium would be expected to result in capillary leakage and an increase in the tissues' water content. Total tissue water (TTW) in different organs was therefore studied in freely moving rats exposed to 100% O2 at normobaric pressure for 24 or 48 h, and compared to air-breathing control rats. The TTW for the following tissues was measured: Trachea, left bronchus, left lung, left and right ventricle, left kidney, skin (left paw-hindlimb), skin (back of the rat), left brain, left eye and thigh muscle left side. There was a significant increase in TTW of the lung accompanied by pleural effusion after 48 h of oxygen exposure as expected in all exposed animals. There was a small increase in TTW of the paw only, and a small decrease or no change in other tissues after 24 and 48 h of exposure. We conclude that there is no evidence of systemic capillary dysfunction as measured by tissue water content after exposure to hyperoxia in a dosage causing pulmonary oedema. [source] Immediate Pathologic Effects on the Vein Wall of Foam SclerotherapyDERMATOLOGIC SURGERY, Issue 10 2007CAMILLO ORSINI MD BACKGROUND During the past 10 years, sclerotherapy has radically changed, the foam sclerotherapy method being better than that of liquid sclerotherapy. OBJECTIVES We have analyzed the immediate pathologic effects on the saphenous vein wall in vivo after sclerotherapy with sodium tetradecyl sulfate (STD) foam. METHODS A group of six patients affected by chronic venous insufficiency, operated on by stripping of the saphenous vein, underwent an intraoperative procedure of sclerotherapy to an isolated but not yet removed tract of saphenous vein with 3% STD foam. RESULTS The pathologic damage of the foam was extremely rapid with complete damage of the endothelium within the first 2 minutes. In the successive 15 and 30 minutes there was edema of the intimal with its progressive separation from the tunica media and the initial formation and adhesion of the thrombus to the tunica media. CONCLUSIONS In this in vivo report we analyze the capacity of 3% STD foam sclerotherapy to damage the saphenous vein wall. The damage is extremely fast and shows the detachment of the intimal and the development of the microthrombus. [source] Comparison of Endovenous Radiofrequency Versus 810 nm Diode Laser Occlusion of Large Veins in an Animal ModelDERMATOLOGIC SURGERY, Issue 1 2002Robert A. Weiss MDArticle first published online: 27 FEB 200 background. Endovenous occlusion using radiofrequency (RF) energy has been shown to be effective for the elimination of sapheno-femoral reflux and subsequent elimination of varicose veins. Recently, endovenous laser occlusion has been introduced with initial clinical reports indicating effective treatment for varicose veins. However, in our practice we note increased peri-operative hematoma and tenderness with the laser. Little is known regarding the mechanism of action of this new laser vein therapy. objective. To better understand the mechanism of action of endovenous laser vs. the endovenous RF procedure in the jugular vein of the goat model. methods. A bilateral comparison was performed using 810 nm diode laser transmitted by a bare-tipped optical fiber vs. the RF delivery by engineered electrodes with a temperature feedback loop using a thermocouple (Closure procedure) in three goat jugular veins. Immediate and one-week results were studied radiographically and histologically. Temperature measurements during laser treatment were performed by using an array of up to five thermocouples, spaced 2 mm apart, placed adjacent to a laser fiber tip during goat jugular vein treatment. results. Immediate findings showed that 100% of the laser-treated veins showed perforations by histologic examination and immediate contrast fluoroscopy. The RF-treated side showed immediate constriction with maintenance of contrast material within the vein lumen and no perforations. The difference in acute vein shrinkage was also dramatic as laser treatments resulted in vein shrinkage of 26%, while RF-treated veins showed a 77% acute reduction in diameter. At one week, extravasated blood that leaked into the surrounding tissue of laser treated veins acutely, continued to occupy space and impinge on surrounding structures including nerves. For the laser treatment, the highest average temperature was 729°C (peak temperature 1334°C) observed flush with the laser fiber tip, while the temperature feedback mechanism of the RF method maintains temperatures at the electrodes of 85°C. conclusion. Vein perforations, extremely high intravascular temperatures, failure to cause significant collagen shrinkage, and intact endothelium in an animal model justify a closer look at the human clinical application of the 810 nm endovenous laser technique. Extravasated blood impinging on adjacent structures may theoretically lead to increased peri-operative hematoma and tenderness. Further study and clinical investigation is warranted. [source] Gene transfer by electroporation into hemogenic endothelium in the avian embryoDEVELOPMENTAL DYNAMICS, Issue 6 2010Catalina Ana Rosselló Abstract Hematopoiesis is the dynamic process whereby blood cells are continuously produced in an organism. Blood cell production is sustained by a population of self-renewing multipotent hematopoietic stem cells (HSCs) throughout the life of an organism. Cells with definitive HSC properties appear in the mid-gestation embryo as dense clusters of cells budding from the floor of the aorta, and that of the vitelline and umbilical arteries in the aorta-gonads-mesonephros region. Attempts to genetically modify the aortic floor from which these HSCs arise have been unsuccessful in the mouse, since the regulation of gene expression in the hemogenic endothelium is largely unknown. Here we report the implementation of gene transfer by electroporation into dorsal aortic endothelial cells in the chick embryo. This approach provides a quick and reproducible method of generating gain/loss-of-function models to investigate the function of genes involved in HSC birth. Developmental Dynamics 239:1748,1754, 2010. © 2010 Wiley-Liss, Inc. [source] Expression of the hyaluronan receptor LYVE-1 is not restricted to the lymphatic vasculature; LYVE-1 is also expressed on embryonic blood vesselsDEVELOPMENTAL DYNAMICS, Issue 7 2008Emma J. Gordon Abstract Expression of the hyaluronan receptor LYVE-1 is one of few available criteria used to discriminate lymphatic vessels from blood vessels. Until now, endothelial LYVE-1 expression was reported to be restricted to lymphatic vessels and to lymph node, liver, and spleen sinuses. Here, we provide the first evidence that LYVE-1 is expressed on blood vessels of the yolk sac during mouse embryogenesis. LYVE-1 is ubiquitously expressed in the yolk sac capillary plexus at E9.5, then becomes progressively down-regulated on arterial endothelium during vascular remodelling. LYVE-1 is also expressed on intra-embryonic arterial and venous endothelium at early embryonic stages and on endothelial cells of the lung and endocardium throughout embryogenesis. These findings have important implications for the use of LYVE-1 as a specific marker of the lymphatic vasculature during embryogenesis and neo-lymphangiogenesis. Our data are also the first demonstration, to our knowledge, that the mouse yolk sac is devoid of lymphatic vessels. Developmental Dynamics 237:1901,1909, 2008. © 2008 Wiley-Liss, Inc. [source] Dlk1 expression marks developing endothelium and sites of branching morphogenesis in the mouse embryo and placentaDEVELOPMENTAL DYNAMICS, Issue 4 2006Aleksey Yevtodiyenko Abstract The protein product of the Delta-like 1 (Dlk1) gene belongs to the Delta-Notch family of signaling molecules, proteins involved in cell fate determination in many tissues during development. The DLK1 protein is believed to function as a growth factor, maintaining the proliferative state of undifferentiated cells, and is usually down-regulated as immature cells differentiate. The expression pattern of the DLK1 protein has been described in certain human tissues; however, Dlk1 expression is not well understood in the mouse, the most tractable mammalian genetic model system. To better understand the role of Dlk1 in embryonic development, the tissue-specific expression pattern of Dlk1 mRNA during mouse embryogenesis was analyzed by in situ hybridization. In embryonic day 12.5 (e12.5) embryos, high levels of Dlk1 were found in the developing pituitary, pancreas, lung, adrenal, and many mesodermally derived tissues. Strikingly, Dlk1 expression also marks the growing branches of organs that develop through the process of branching morphogenesis. At e16.5, Dlk1 expression is down-regulated in most tissues but remains in the pituitary, the adrenal gland, and in skeletal muscle. In the placenta, expression of Dlk1 is detected in endothelial cells lining the fetal blood vessels of the labyrinth. This pattern is distinct from that seen in the human placenta and suggests a role for Dlk1 in regulating maternal,fetal interactions. Developmental Dynamics 235:1115,1123, 2006. © 2006 Wiley-Liss, Inc. [source] Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafishDEVELOPMENTAL DYNAMICS, Issue 1 2006You Mie Lee Abstract Vascular endothelial growth factor-receptors (VEGF-Rs) are pivotal regulators of vascular development, but a specific role for these receptors in the formation of heart valves has not been identified. We took advantage of small molecule inhibitors of VEGF-R signaling and showed that blocking VEGF-R signaling with receptor selective tyrosine kinase inhibitors, PTK 787 and AAC 787, from 17,21 hr post-fertilization (hpf) in zebrafish embryos resulted in a functional and structural defect in cardiac valve development. Regurgitation of blood between the two chambers of the heart, as well as a loss of cell-restricted expression of the valve differentiation markers notch 1b and bone morphogenetic protein-4 (bmp - 4), was readily apparent in treated embryos. In addition, microangiography revealed a loss of a definitive atrioventricular constriction in treated embryos. Taken together, these data demonstrate a novel function for VEGF-Rs in the endocardial endothelium of the developing cardiac valve. Developmental Dynamics 235:29,37, 2006. © 2005 Wiley-Liss, Inc. [source] Early expression of endomucin on endothelium of the mouse embryo and on putative hematopoietic clusters in the dorsal aortaDEVELOPMENTAL DYNAMICS, Issue 3 2001Gertrud Brachtendorf Abstract Endomucin is a recently identified sialomucin that is specifically expressed on endothelium of the adult mouse. Here, we have analysed the expression of endomucin during development of the vascular system by immunohistochemistry by using three monoclonal antibodies (mAb). We demonstrate that two of the mAb, V.5C7 and V.1A7, recognize epitopes on the nonglycosylated protein, because they recognize the antigen when it is synthesized as a bacterial fusion protein and when it is in vitro translated in a membrane-free reticulocyte lysate. During in vitro differentiation of embryonic stem cells to endothelial cells, endomucin is expressed at day 6 after onset of differentiation, 1 day later than PECAM-1. During differentiation of the mouse embryo, endomucin is first detected at E8.0 in all embryonic blood vessels detectable at this stage but is absent in blood islands of the yolk sac. Analysing the paraaortic-splanchnopleura (P-SP) region and the aorta-gonad-mesonephros (AGM) region as sites of intraembryonic hematopoiesis, we found that endothelium of the dorsal aorta is brightly positive for endomucin at E8.5,9.0 and at E11.5. At later stages and in the adult aorta, endothelial staining is strongly reduced and confined to focal areas. Cell clusters associated with the luminal surface of the endothelium of the dorsal aorta could be stained for endomucin and for CD34. At a later stage (E15.5) single leukocytes in the lumen of large venules were stained for endomucin. We conclude that endomucin is an early endothelial-specific antigen that is also expressed on putative hematopoietic progenitor cells. © 2001 Wiley-Liss, Inc. [source] Potential manipulation of endothelial progenitor cells in diabetes and its complicationsDIABETES OBESITY & METABOLISM, Issue 7 2010G. P. Fadini Diabetes mellitus increases cardiovascular risk through its negative impact on vascular endothelium. Although glucotoxicity and lipotoxicity account for endothelial cell damage, endothelial repair is also affected by diabetes. Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. For these reasons, EPCs are thought to have a protective impact within the cardiovascular system. In addition, EPCs appear to modulate the functioning of other organs, providing neurotropic signals and promoting repair of the glomerular endothelium. The exact mechanisms by which EPCs provide cardiovascular protection are unknown and the definition of EPCs is not standardized. Notwithstanding these limitations, the literature consistently indicates that EPCs are altered in type 1 and type 2 diabetes and in virtually all diabetic complications. Moreover, experimental models suggest that EPC-based therapies might help prevent or reverse the features of end-organ complications. This identifies EPCs as having a novel pathogenic role in diabetes and being a potential therapeutic target. Several ways of favourably modulating EPCs have been identified, including lifestyle intervention, commonly used medications and cell-based approaches. Herein, we provide a comprehensive overview of EPC pathophysiology and the potential for EPC modulation in diabetes. [source] A cardiologist view of vascular disease in diabetesDIABETES OBESITY & METABOLISM, Issue 4 2008Christopher J. Lockhart Diabetes mellitus is a potent risk factor for the development of a wide spectrum of cardiovascular (CV) complications. The complex metabolic milieu accompanying diabetes alters blood rheology, the structure of arteries and disrupts the homeostatic functions of the endothelium. These changes act as the substrate for end-organ damage and the occurrence of CV events. In those who develop acute coronary syndromes, patients with diabetes are more likely to die, both in the acute phase and during follow-up. Patients with diabetes are also more likely to suffer from chronic cardiac failure, independently of the presence of large vessel disease, and also more likely to develop stroke, renal failure and peripheral vascular disease. Preventing vascular events is the primary goal of therapy. Optimal cardiac care for the patient with diabetes should focus on aggressive management of traditional CV risk factors to optimize blood glucose, lipid and blood pressure control. Targeting medical therapy to improve plaque stability and diminish platelet hyper-responsiveness reduces the frequency of events associated with atherosclerotic plaque burden. In patients with critical lesions, revascularization strategies, either percutaneous or surgical, will often be necessary to improve symptoms and prevent vascular events. Improved understanding of the vascular biology will be crucial for the development of new therapeutic agents to prevent CV events and improve outcomes in patients with diabetes. [source] The metabolic syndrome: evolving evidence that thiazolidinediones provide rational therapyDIABETES OBESITY & METABOLISM, Issue 4 2006Kathleen L. Wyne The metabolic syndrome, also known as the dysmetabolic syndrome, syndrome X or the insulin resistance syndrome, refers to the clustering of cardiovascular disease risk factors that are present in many individuals who are at increased risk for both cardiovascular events and type 2 diabetes. Prediabetic subjects typically exhibit an atherogenic pattern of cardiovascular risks that is associated with hyperinsulinaemia. Thus, identification of components of the metabolic syndrome is important if patients are to be treated early enough to prevent cardiovascular events and other complications related to diabetes. Therapies targeted to specific components of the metabolic syndrome such as improving glycaemic control, managing dyslipidaemia and reducing the prothrombotic state should help to minimize cardiovascular risk, particularly if initiated early. Traditional pharmacologic agents used to manage the individual components of the metabolic syndrome do not typically impact the other components. The thiazolidinediones, a new class of agents that improve insulin resistance, have the ability, in addition to their glucose-lowering effects, to exert several powerful anti-atherogenic properties, including anti-inflammatory effects in the vascular endothelium, redistribution of visceral fat and reduction of insulin resistance, hyperinsulinaemia and hyperproinsulinaemia. This makes the thiazolidinediones ideal candidates for the early treatment of many components associated with the metabolic syndrome. [source] The effects of lipid-lowering drug therapy on cardiovascular responsiveness in type 2 diabetic patientsDIABETES OBESITY & METABOLISM, Issue 1 2006Laurence Guy HowesArticle first published online: 18 MAR 200 Type 2 diabetes is associated with a high prevalence of dyslipidaemia and a high incidence of cardiovascular disease. Lipid lowering therapy with HMG Co-A reductase inhibitors (statins) reduce the risk of cardiovascular events in type 2 diabetic and non-diabetic patients, effects which are believed to be partly due to improvements in vascular function. The aetiology of abnormal vascular function in type 2 diabetics is likely to be multifactorial and the pattern of vascular dysfunction in type 2 diabetes may differ from that which occurs in non-diabetic patients with dyslipidaemia. Abnormalities in endothelium derived hyperpolarising factor (EDHF) mediated vasodilation in resistance vessels may be more prominent in both type 1 and type 2 diabetes than in non-diabetic patients with endothelial dysfunction. The effects of lipid lowering therapy on vascular responsiveness may differ in type 2 diabetic patients from those found in non-diabetic patients. Statin therapy does not appear to improve responses to endothelial dependent vasodilators in type 2 diabetics, but may alter the ratio between nitric oxide (NO) and EDHF mediated responses. Fibrate therapy improves flow mediated dilation of brachial arteries in type 2 diabetic patients, but only appears to improve endothelium dependant vasodilator responses in resistance vessels when given in conjunction with co-enzyme Q. [source] Relationship between protective effects of rosiglitazone on endothelium and endogenous nitric oxide synthase inhibitor in streptozotocin-induced diabetic rats and cultured endothelial cellsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2007Shan Wang Abstract Background Previous investigations have indicated that the level of asymmetric dimethylarginine (ADMA) is increased in diabetic patients and animals, and rosiglitazone has a protective effect on the endothelium. In the present study, we tested the relationship between protective effects of rosiglitazone and ADMA in streptozotocin (STZ)-induced diabetic rats and cultured endothelial cells. Methods Blood samples were collected from carotid artery. Vasodilator responses to acetylcholine (ACh) in the isolated aortic rings were measured, and serum concentrations of glucose, lipid, nitrite/nitrate, ADMA and tumour necrosis factor-, (TNF-,) were determined. Cultured endothelial cells were treated with ADMA, and the concentrations of intercellular adhesion molecule (ICAM-1), TNF-,, and the activity of nuclear factor-,B (NF-,B) were determined. Results Vasodilator responses to ACh were decreased markedly and the serum concentrations of TNF-,, nitrite/nitrate and ADMA were increased significantly in diabetic rats. Rosiglitazone (3, 10 or 30 mg/kg) produced a significant reduction of the inhibition of vasodilator responses to ACh, but had no effect on the serum concentrations of glucose, lipid, nitrite/nitrate and ADMA in diabetic rats. ADMA (30 µM) significantly increased the activity of NF-,B and elevated the levels of ICAM-1 and TNF-,, and pre-treatment with rosiglitazone (10 or 30 µM) markedly inhibited the increased activity of NF-,B and reduced the elevated levels of TNF-, and ICAM-1 induced by ADMA in cultured endothelial cells. Conclusions Rosiglitazone improves endothelial function in diabetic rats, which is related to the reduction of the inflammatory response induced by ADMA. Copyright © 2006 John Wiley & Sons, Ltd. [source] Insulin treatment and cardiovascular disease; friend or foe?DIABETIC MEDICINE, Issue 2 2005A point of view Abstract Background Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature. Summary of comment Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk. Conclusion Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area. [source] CPU-86017 improves the compromised blood,brain barrier permeability mediated by impaired endothelial no system and oxidative stress caused by L -thyroxineDRUG DEVELOPMENT RESEARCH, Issue 3 2005Rong-Hui Du Abstract Impaired endothelial cell (EC) function leads to alterations in the permeability of the blood,brain barrier (BBB). There are two aspects of the transport through the BBB: from the blood to the brain (influx) and from the brain to the blood (efflux). An impaired EC model induced by L -thyroxine that compromises the influx and efflux properties of the BBB was used to assess responses to the intervention of CPU-86017 (an antioxidant and calcium channel blocker) and propranolol. CPU-86017 (t1/2=1.5 h) was also used as a target drug, leaving no traces in the brain and blood 24 h after administration. The permeability of the BBB was evaluated by using CPU-86017 after iv and icv injection and concentrations in the blood and brain being measured by high-performance liquid chromatography. The bidirectional permeability of CPU-86017 was impaired and associated with a reduced NO bioavailability assessed functionally by the vasoactivity in the model. Partial relief of NO bioavailability and oxidative stress induced by propranolol was consistent with a recovery of BBB efflux alone. Complete recovery in the efflux and influx of the BBB by CPU-86017 was a result of the complete restoration of NO bioavailability and reduction in oxidative stress. Normal BBB influx is dependent on an intact endothelial NO system, and efflux could be restored easily by partial improvement of NO bioavailability. CPU-86017 is thus more effective than propranolol in protecting the endothelium from damage produced by L -thyroxine through oxidative stress. Drug Dev. Res. 64:145,156, 2005. © 2005 Wiley-Liss, Inc. [source] Xanthine-analog, KMUP-2, enhances cyclic GMP and K+ channel activities in rabbit aorta and corpus cavernosum with associated penile erectionDRUG DEVELOPMENT RESEARCH, Issue 3 2002Rong-Jyh Lin Abstract The pharmacological properties of KMUP-2 were examined in isolated rabbit aorta and corpus cavernosum smooth muscle (CCSM). KMUP-2 caused relaxations that were attenuated by removed endothelium, high K+, and pretreatment with the soluble guanylate cyclase (sGC) inhibitors methylene blue (10 ,M) and ODQ (1 ,M), a NOS inhibitor, L-NAME (100 ,M), a K+ channel blocker TEA (10 mM), a KATP channel blocker glibenclamide (1 ,M), a voltage-dependent K+ channel blocker 4-AP (100 ,M), and the Ca2+ -dependent K+ channel blockers apamin (1 ,M) and charybdotoxin (ChTX, 0.1 ,M). The relaxant responses of KMUP-2 (0.01, 0.05, 0.1 ,M) together with a PDE inhibitor, IBMX (0.5 ,M), had additive effects on rabbit aorta and CCSM. Additionally, KMUP-2 (100 ,M) also affected cGMP metabolism, due to its inhibiting activity on PDE in human platelets. KMUP-2 (0.1,100 ,M) further induced an increase of intracellular cGMP levels in the primary cultured rabbit aortic and CCSM cells. These increases in cGMP content were abolished in the presence of methylene blue (100 ,M) and ODQ (10 ,M). Obviously, the relaxant effects of KMUP-2 on rabbit isolated tissues are more sensitive in CCSM than in aorta. Moreover, KMUP-2 also stimulated NO/sGC/cGMP pathway and subsequent elevation of cGMP by blockade of PDE and enhanced opening of K+ channels in rabbit aorta and CCSM. KMUP-2 (0.2, 0.4, 0.6 mg/kg), similar to KMUP-1 and sildenafil, caused increases of intracavernous pressure (ICP) and duration of tumescene (DT) in a dose-dependent manner. It is concluded that both the increases of cGMP and the opening activity of K+ channels play prominent roles in KMUP-2-induced aortic smooth muscle and CCSM relaxation and increases of ICP in rabbits. Drug Dev. Res. 55:162,172, 2002. © 2002 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||||||||