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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of coronary microvascular resistance is not distributed uniformly, but varies across different segments of the vasculature. Differences in regulatory mechanisms, including metabolic, myogenic, alpha-adrenergic and endothelial cell mediated, help define a series of coronary vascular microdomains. Generally, small arterioles, those less than 100 microns in diameter, respond differently than large arterioles or small arteries. This segmental distribution suggests an integrative hypothesis of regulation whereby a variety of mechanisms play a role in the overall response. One pathology that disturbs these control mechanisms in the microcirculation of the heart is reperfusion injury. Reperfusion injury of the microcirculation has as its primary target the vascular endothelium. The mechanisms responsible for reduced endothelium-dependent relaxation, likely include a reduction in the levels of tetrahydrobiopterin, a co-factor of nitric oxide synthase. Manipulation of levels of tetrahydrobiopterin in endothelial cells may be beneficial in the prevention of the pathophysiological sequelae of reperfusion injury in the coronary microcirculation.
J Mol Cell Cardiol 1998 Dec
PMID:Control of microvascular resistance in physiological conditions and reperfusion. 999 May 26

Heparin, which is widely used clinically, has recently been shown to have specific properties affecting the vascular endothelium. We hypothesized that heparin stimulates endothelial nitric oxide synthase (eNOS) activity by a mechanism independent of its anticoagulant properties and dependent on an inhibitory guanine nucleotide regulatory protein (Gi). We determined the effect of both heparin and N-acetyl heparin (Non-Hep), a heparin derivative without anticoagulant properties, on eNOS activity in cultured bovine aortic endothelial cells and on endothelium-dependent relaxation in isolated vascular rings. The eNOS activity was determined by measuring both citrulline and nitric oxide (NO) metabolite formation. Heparin and Non-Hep dose-dependently increased basal eNOS activity (ED50 1.0 microgram/ml or 0.15 U/ml), an effect that was significantly inhibited by pertussis toxin (100 ng/ml), a Gi-protein inhibitor. Agonist-stimulated (acetylcholine, 10 microM) eNOS activity was potentiated following pre-treatment with both heparin and Non-Hep and reversed by pertussis toxin. Heparin and Non-Hep induced a dose-dependent relaxation in preconstricted thoracic aortic rings, an effect that was significantly inhibited by pertussis toxin, endothelial inactivation (following treatment with sodium deoxycholate) and NG-nitro-L-arginine-methyl ester (L-NAME). We conclude that heparin and non-anticoagulant heparin induce endothelium-dependent relaxation following activation of eNOS by a mechanism involving a Gi-protein. Administration of heparin derivatives without anticoagulant properties may have therapeutic implications for the preservation of eNOS in conditions characterized by endothelial dysfunction.
J Mol Cell Cardiol 1998 Dec
PMID:Non-anticoagulant heparin increases endothelial nitric oxide synthase activity: role of inhibitory guanine nucleotide proteins. 999 May 38

The purpose of this study was to localize intercellular adhesion molecule (ICAM)-1 and ICAM-2 in human endometrium and myometrium throughout the menstrual cycle, and to determine whether the expression of these molecules is regulated by interferon (IFN)-gamma. ICAM-1 and ICAM-2 distribution was examined in endometrial biopsies by immunocytochemistry, and Northern blotting was used to quantify ICAM-1 and ICAM-2 mRNA expression in isolated endometrial glands. Stromal fibroblast cultures were exposed to IFN-gamma and the effect on expression of ICAM-1 and ICAM-2 was determined by immunocytochemistry and Northern blotting. ICAM-1 was localized in vivo to the apical surface of the glandular epithelium, the vascular endothelium and endometrial stromal cells throughout the menstrual cycle. Stromal expression of ICAM-1 was up-regulated in menstrual specimens. Northern blotting confirmed the presence of ICAM-1 mRNA in isolated endometrial glands. The expression of ICAM-1 antigen and message was increased in stromal cell culture after incubation with IFN-gamma in a time-dependent manner, suggesting that this cytokine stimulates the expression of ICAM-1 in the endometrial stroma. ICAM-2 antigen expression was restricted to the vascular endothelium. ICAM-2 mRNA was absent in endometrial glands. The widespread distribution of ICAM-1 in human endometrium suggests that this molecule is involved in the process of menstruation, the functioning of glands, blood vessels and stroma, and in regulating leukocyte trafficking into the tissue. ICAM-2 is restricted to the vascular endothelium where it might modulate leukocyte invasion of the stroma and myometrial connective tissue.
Mol Hum Reprod 1999 Jan
PMID:Expression of intercellular adhesion molecules ICAM-1 and ICAM-2 in human endometrium: regulation by interferon-gamma. 1005 Jun 64

The vascular endothelium plays a key role in the local regulation of vascular tone by the release of vasodilator substances (i.e. endothelium-derived relaxing factor (EDRF = nitric oxide, NO) and prostacyclin) and vasoconstrictor substances (i.e. thromboxane A2, free radicals, or endothelin). Using either agents like acetylcholine or changes in flow to stimulate the release of EDRF (NO), clinical studies have revealed the importance of EDRF in both basal and stimulated control of vascular tone in large epicardial coronary arteries and in the coronary microcirculation. The regulatory function of the endothelium is altered by cardiovascular risk factors or disorders such as hypercholesterolemia, chronic smoking, hypertension or chronic heart failure. Endothelial dysfunction appears to have detrimental functional consequences as well as adverse longterm effects, including vascular remodelling. Endothelial dysfunction is associated with impaired tissue perfusion particularly during stress and paradoxical vasoconstriction of large conduit vessels including the coronary arteries. These effects may cause or contribute to myocardial ischemia. Several mechanisms may be involved in the development of endothelial dysfunction, such as reduced synthesis and release of EDRF or enhanced inactivation of EDRF after its release from endothelial cells by radicals or oxidized low-density lipoprotein (LDL). Increased plasma levels of oxidized LDL have been noted in chronic smokers and are related to the extent endothelial dysfunction, raising the possibility that chronic smoking potentiates endothelial dysfunction by increasing circulating and tissue levels of oxidized LDL. In heart failure, cytokines and/or reduced flow (reflecting reduced shear stress) may be involved in the development of endothelial dysfunction and can be reversed by physical training. Other mechanisms include an activated renin-angiotensin system (i.e. postmyocardial infarction) with increased breakdown of bradykinin by enhanced angiotensin converting enzyme (ACE) activity. There is evidence that endogenous bradykinin is involved in coronary vasomotor control both in coronary conduit and resistance vessels. ACE inhibitors enhance endothelial function by a bradykinin-dependent mechanism and probably also by blunting the generation of superoxide anion. Endothelial dysfunction appears to be reversible by administering L-arginine, the precursor of nitric oxide, lowering cholesterol levels, physical training, antioxidants such as vitamin C, or ACE inhibition.
J Mol Cell Cardiol 1999 Jan
PMID:Endothelial dysfunction in human disease. 1007 15

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction as well as myocardial injury. These effects are due in large part to endothelial dysfunction leading to an upregulation of cell adhesion molecules and subsequent neutrophil induced cardiac injury. The proteasome inhibitor, PS-519, has been shown to attenuate leukocyte-endothelial cell interactions. We tested the effects of PS-519 on neutrophil mediated cardiac dysfunction in ischemia/reperfusion. This study examines the effects of PS-519 in a neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of PS-519 (0.01, 0.1, 0.3, 1.0 mg/kg) to I/R hearts perfused with PMNs improved coronary flow, and preserved left ventricular developed pressure (LVDP) and + dP/dt max as indices of cardiac contractile function. At 1.0 mg/kg, PS-519 treated hearts exhibited a final LVDP of 98 +/- 3% of initial compared to 52 +/- 8% in I/R hearts receiving only vehicle (P < 0.001). In addition, PS-519 significantly reduced PMN accumulation in the ischemic myocardium from 25.1 +/- 2.1 PMNs/mm2 in untreated hearts to 7.3 PMNs/mm2, and attenuated P-selectin surface expression on coronary vascular endothelium from 7.1 +/- 0.3% to 1.4 +/- 0.2% (P < 0.01). These results provide evidence that PS-519 is a potent and effective cardioprotective agent that inhibits P-selectin leukocyte-endothelial cell interactions and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion.
J Mol Cell Cardiol 1999 Feb
PMID:Cardioprotective effects of a novel proteasome inhibitor following ischemia and reperfusion in the isolated perfused rat heart. 1009 58

Fetal placental vessels develop and adapt in order to supply the fetus with nutrients. Immunostaining by antibodies against blood clotting factors, cell-cell and cell-matrix adhesion molecules, intermediate and contractile filaments, matrix components and enzymes give an overall view useful in assessing cell differentiation in placental villi. Endothelial cells stained positively for thrombomodulin, von Willebrand factor, CD34, CD31, cadherin-5, phalloidin and alpha 3-integrin. Trophoblastic cells were positive for cytokeratin, alpha 5 and alpha V integrins, L-prolyl hydroxylase and phalloidin. Myocytes from the media of stem villi exhibited positive vimentin, desmin, alpha-sm-actin and sm-myosin reactions but were CD26 negative. Myofibroblasts were vimentin, desmin, CD26, alpha-sm-actin and sm-myosin positive. Perivascular cells of intermediate and terminal villi were alpha-sm-actin, sm-myosin and anti-high molecular weight melanoma associated antigen (HMWMAA) positive. Trophoblastic and endothelial basement membranes were collagen IV positive. The most specific endothelial markers were cadherin-5, observed only at paracellular clefts, and von Willebrand factor. For perivascular cells, alpha-sm-actin, sm-myosin and HMWMAA provided a specific labeling. Differences in labeling intensity were noted along the cross section of the villous tree (vimentin, desmin, actin, myosin inward gradient). A continuity in the contractile function along the vessel length was indicated by alpha-sm-actin and sm-myosin positive cells, contrasting with the decreased von Willebrand reaction intensity. These data are discussed in relation to cell function and compared to cell culture results.
Cell Mol Biol (Noisy-le-grand) 1999 Feb
PMID:Immunostaining of vascular, perivascular cells and stromal components in human placental villi. 1009 44

The monolayer of endothelial cells that coats the luminal surface of the vessel wall has numerous physiological functions, including the prevention of coagulation, control of vascular permeability, maintenance of vascular tone and regulation of leukocyte extravasation. Recently, we detected functional Fas ligand (FasL) expression on the endothelial lining of blood vessels. FasL induces apoptotic cell death in the multitude of cell types that express its receptor, Fas. Here, we review the function of vascular endothelium in controlling leukocyte extravasation, and illustrate how the regulation of endothelial FasL expression might contribute to this process. We also describe the role of leukocyte extravasation in angiogenesis and atherosclerosis, and we suggest that FasL gene transfer might provide a means of treating diseases of the proliferative vessel wall, particularly those that result from the detrimental infiltration of inflammatory cells.
Mol Med Today 1999 Feb
PMID:Is extravasation a Fas-regulated process? 1020 Sep 46

The facultative intracellular bacterium Listeria monocytogenes is an invasive pathogen that crosses the vascular endothelium and disseminates to the placenta and the central nervous system. Its interaction with endothelial cells is crucial for the pathogenesis of listeriosis. By infecting in vitro human umbilical vein endothelial cells (HUVEC) with L. monocytogenes, we found that wild-type bacteria induced the expression of the adhesion molecules (ICAM-1 and E-selectin), chemokine secretion (IL-8 and monocyte chemotactic protein-1) and NF-kappa B nuclear translocation. The activation of HUVEC required viable bacteria and was abolished in prfA-deficient mutants of L. monocytogenes, suggesting that virulence genes are associated with endothelial cell activation. Using a genetic approach with mutants of virulence genes, we found that listeriolysin O (LLO)-deficient mutants inactivated in the hly gene did not induce HUVEC activation, as opposed to mutants inactivated in the other virulence genes. Adhesion molecule expression, chemokine secretion and NF-kappa B activation were fully restored by a strain of Listeria innocua transformed with the hly gene encoding LLO. The relevance in vivo of endothelial cell activation for listerial pathogenesis was investigated in transgenic mice carrying an NF-kappa B-responsive lacZ reporter gene. NF-kappa B activation was visualized by a strong lacZ expression in endothelial cells of capillaries of mice infected with a virulent haemolytic strain, but was not seen in those infected with a non-haemolytic isogenic mutant. Direct evidence that LLO is involved in NF-kappa B activation in transgenic mice was provided by injecting intravenously purified LLO, thus inducing stimulation of NF-kappa B in endothelial cells of blood capillaries. Our results demonstrate that functional listeriolysin O secreted by bacteria contributes as a potent inflammatory stimulus to inducing endothelial cell activation during the infectious process.
Mol Microbiol 1999 Mar
PMID:Listeriolysin O-dependent activation of endothelial cells during infection with Listeria monocytogenes: activation of NF-kappa B and upregulation of adhesion molecules and chemokines. 1020 44

Adherens junctions of the endothelium play a key role in the maintenance of endothelial permeability and are composed of the vascular endothelial (VE)-cadherin/catenin adhesion complex. We report that following tumour cell (MDA MB231 cells) adherence to the HUVECs, there was a rapid (within 5 min) redistribution of VE-cadherin, resulting in its transient loss from regions of endothelial cell-cell contact. The molecule gradually reorganised within the endothelial cell contacts after this time. It was further shown that the overall expression of VE-cadherin did not change, however, the amount of alpha- and beta-catenins coprecipitated with VE-cadherin markedly decreased after 5 min of tumour cell adhesion to the HUVECs. Immunoprobing of these samples with anti-phosphotyrosine antibodies demonstrated that the tyrosine phosphorylation of VE-cadherin was significantly increased following 5 min of tumour cell adhesion. Together, these results suggest that the adhesion of tumour cells to HUVEC promotes the redistribution of VE-cadherin from interendothelial adherens junctions, an effect that may be attributed to the increase in tyrosine phosphorylation of members of the VE-cadherin/catenin adhesion complex. This, in turn, may increase vascular endothelial permeability and facilitate the transendothelial migration of tumour cells during extravasation.
Int J Mol Med 1999 Aug
PMID:Phosphorylation and disorganization of vascular-endothelial cadherin in interaction between breast cancer and vascular endothelial cells. 1040 88

The frictional forces associated with blood flow expose vascular endothelium in arteries to a complex and highly dynamic shear stress distribution. The ability of endothelial cells to respond to shear stress is essential for arterial vasoregulation in response to acute hemodynamic changes and for vascular wall remodeling following chronic changes in blood flow. Furthermore, endothelial responsiveness to shear stress may play a role in the localization of early atherosclerotic lesions. Shear stress elicits a wide range of humoral, metabolic, and structural responses in endothelial cells. These include activation of ion channels and of G proteins, induction of oscillations in intracellular calcium concentration, alterations in the expression of various important genes, and extensive cytoskeletal reorganization. Mechanisms of shear stress sensing and transmission in endothelium are discussed in light of the complex shear stress distribution to which endothelial cells are exposed in vivo and with particular emphasis on the potentially central role of flow-sensitive ion channels and the cellular cytoskeleton. Finally, the ability of endothelial cells to distinguish among and to respond differentially to different types of shear stress is highlighted.
Int J Mol Med 1999 Oct
PMID:Responsiveness of vascular endothelium to shear stress: potential role of ion channels and cellular cytoskeleton (review). 1049 72


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