Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clearance of thrombin seems to occur at more than one site and by different mechanisms. This contributes to maintaining thrombin at the right concentrations to act optimally on its various substrates, and thus, to produce the proper amount of proteolytic conversions so that coagulation is precisely controlled. The vascular endothelium plays a major role in thrombin regulation and clearance. It contains heparin-like binding sites and thrombomodulin which serve as cofactors for the thrombin-antithrombin III reaction and the activation of protein C, respectively. In addition, thrombomodulin also serves as a receptor for endothelial cell mediated thrombin endocytosis. Thrombin clearance, which occurs following reaction with antithrombin III or thrombomodulin, probably takes place at different stages in hemostasis.
Mol Cell Biochem 1986 Aug
PMID:Clearance of thrombin in vivo: significance of alternative pathways. 302 20

Monoclonal antibodies MRC OX-45 and OX-46 detect identical or juxtaposed antigenic determinants on a novel rat membrane molecule that plays a possible role in macrophage suppression of antigen-induced T-cell responses. These antibodies react with most mature hematopoietic cells and their bone-marrow precursors, vascular endothelium and some connective tissue. The OX-45 antigens were purified from brain (mainly endothelium) and spleen by immunoaffinity chromatography, and were found to be glycoproteins with apparent Mr 43,000 and 45,000, respectively, as determined by SDS-PAGE analysis. The amino acid compositions of the two preparations were very similar but with no distinguishing features. The broad pattern of distribution was not the result of fortuitous cross-reaction of the MAbs as a single N-terminal sequence was obtained from mixed spleen populations of cells. Carbohydrate compositions of the brain and spleen molecules differed both in absolute amount (22 and 41% by weight, respectively) and in the ratios of various saccharides reflecting overall differences in the patterns of glycosylation between the two tissues. MRC OX-45 IgG showed an heterogeneity in the Mr of its H chain due to the attachment, in some molecules, of carbohydrate structures to the Fd fragment.
Mol Immunol 1986 Sep
PMID:MRC OX-45 antigen: a leucocyte/endothelium rat membrane glycoprotein of 45,000 molecular weight. 353 34

Four cases of Ewing's sarcoma, three in bone and one from an extraskeletal site, were studied immunohistologically using monospecific antibodies against intermediate filament proteins of keratin, vimentin, desmin and neurofilament types. All cases were also evaluated for the presence of Factor VIII-related antigen (FVIIIR:Ag) and for the binding of Ulex europaeus I lectin (UEA I), both of which are endothelial markers. In all cases the tumor cells contained vimentin but not keratin, desmin or neurofilaments. The tumor cells could not be decorated with either anti-FVIIIR:Ag or UEA I, whereas the vascular endothelium was positive for both markers. The vimentin-positivity indicates a mesenchymal derivation of Ewing's sarcoma, while the lack of endothelial markers argues against the proposed endothelial origin of this tumor.
Virchows Arch B Cell Pathol Incl Mol Pathol 1982
PMID:Histogenesis of Ewing's sarcoma. An evaluation of intermediate filaments and endothelial cell markers. 613 72

We have generated hybridomas which secrete monoclonal antibodies to the AT1 subtype of the angiotensin II receptor (AT1 receptor). These were obtained after immunization of Balb C/c mice with synthetic peptides representing sequences from either the extracellular domain (residues 8-17) or the intracellular domain (residues 229-237) of the AT1 receptor. Hybridoma populations were first screened for the production of antibodies which bound to rat liver cells. Further selection, and cloning by limiting dilution, was carried out for antibodies which bound specifically to rat adrenal glomerulosa cells. Confirmation that the antibody designated 6313/G2 interacted with the angiotensin II receptor was obtained using COS-7 cells transfected with AT1A receptor cDNA. In particular, the initial characterization of 6313/G2 showed specific immunofluorescence of vascular endothelium.
J Mol Endocrinol 1993 Oct
PMID:A monoclonal antibody to a conserved sequence in the extracellular domain recognizes the angiotensin II AT1 receptor in mammalian target tissues. 750 80

Destruction of pulmonary endothelial cells is characteristic of hyperoxic lung injury. During recovery from hyperoxia, pulmonary endothelial cells proliferate to regenerate the vascular endothelium. Vascular endothelial growth factor (VEGF) is a peptide growth factor that is mitogenic specifically for endothelial cells. We hypothesized that VEGF messenger RNA (mRNA) increases during recovery from acute hyperoxic lung injury. Adult rabbits were exposed to 100% oxygen for 64 h and allowed to recover in air for 0, 1, 3, and 5 days. In situ hybridization showed increased VEGF expression in alveolar epithelial cells beginning at 1 day recovery. By 3 days recovery the message was in alveolar epithelial cells throughout the lung. Compared with alveolar epithelial cells, little or no expression was noted in large vessel endothelial cells, airway cells, or smooth muscle cells. Combined in situ hybridization for VEGF and immunostaining for macrophages and other mesenchymal cells found no VEGF message in those cell types. Isolated alveolar macrophages had no detectable VEGF message. Cells expressing VEGF mRNA were enriched in alveolar type II cell preparations from recovering lung. Double in situ hybridization for VEGF and surfactant protein-C (SP-C) showed co-expression in a population of type II cells, but with an inverse relationship: cells with abundant VEGF mRNA did not have abundant SP-C mRNA. Type II cells in vitro expressed VEGF message, but only when the SP-C message abundance was relatively low. We conclude that alveolar type II cells express increased VEGF mRNA during recovery from acute hyperoxia. These findings are consistent with a role for VEGF in regulating microvascular endothelial repair after oxidant injury.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Vascular endothelial growth factor mRNA increases in alveolar epithelial cells during recovery from oxygen injury. 754 67

Endogenous adenosine is produced by the heart during ischemia-reperfusion as a natural cardioprotectant. The benefits of this local protective mechanism can be harnessed by ischemic preconditioning and amplified by drugs such as acadesine, that augment extracellular adenosine levels specifically during an ischemic event. Classically, adenosine production by cardiomyocytes, and measured in the interstitial fluid, is considered the relevant source of this mediator. In contrast, it is proposed that there are two independent sites of adenosine formation in the heart--the myocytes and the endothelial cells, that are differentially regulated. Recent evidence implicates the vascular endothelium as a potentially important site of both adenosine formation and action that subserves the cardioprotective effects of the nucleoside. The mechanisms by which endogenous adenosine protects the heart from ischemia-reperfusion injury require clarification, and may involve different adenosine receptors (A1, A2, and A3) acting through various second messenger systems that contribute to the overall response. Additional studies are required to define the source of adenosine, the mechanisms by which its levels are regulated, and the effector pathways responsible for the myocardial protection observed.
J Mol Cell Cardiol 1995 Apr
PMID:Harnessing an endogenous cardioprotective mechanism: cellular sources and sites of action of adenosine. 756 1

The endothelins (ETs) comprise a family of 21 amino acid peptides, ET-1, ET-2 and ET-3, first demonstrated as products of vascular endothelium. Subsequent work showed that they are also found in non-endothelial cells from a variety of tissues such as breast, parathyroid and adrenal gland. At first, the ETs were recognized for their pressor effects. However, ET administration in vivo initially caused hypotension at low concentrations by triggering the paracrine release of endothelial-derived vasodilators. The ETs exert powerful contractile actions on myometrium and other types of smooth muscle and are mitogenic, or co-mitogenic for fibroblasts, vascular smooth muscle and other cells. Demonstration of extravascular ET in endometrium has revealed a powerful vasoconstrictor which might act on the spiral arterioles to effect a powerful and sustained contraction of vascular smooth muscle. ETs might also contribute to the process of endometrial repair. In addition, the ETs appear to play a fundamental role in the control of uterine function in pregnancy. Effects on myometrial contractility have been implicated in the mechanisms governing the onset of normal and pre-term labour, and the peptides are likely to be key determinants of placental blood flow by binding to vascular smooth muscle receptors in the placenta.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Endothelin expression in the uterus. 762 56

A monocyte chemotactic protein (MCP-1) is thought to play a major role in recruiting monocytes to the vascular endothelium where the adherence of monocytes is one of the earliest events in atherogenesis. We cloned MCP-1 cDNA from a lambda gt 11 cDNA library constructed from human aortic endothelial mRNA to test whether MCP-1 expressed in arterial endothelium is identical to those from other sources. A approximately 670 bp MCP-1 cDNA clone was identified and showed the identical sequence with the ones from other cell lines. Northern blot analysis using this cloned MCP-1 cDNA as probe revealed two hybridizing bands of RNA at 0.68 and 0.77 kb in human aortic, human pulmonary arterial, and human umbilical vein endothelial cell cultures. Primer extension analysis showed that the difference in size (approximately 90 bp) between the two transcripts is not due to a difference at the 5'-noncoding region. The amount of MCP-1 transcripts increased dramatically in aortic endothelial cells when stimulated with recombinant IL-1 alpha (100 units/ml), IL-1 beta (100 units/ml), or TNF-alpha (200 ng/ml). Northern blot and slot blot analysis of RNA isolated from both the endothelium and the underlying vessel wall of freshly removed human arteries and veins showed MCP-1 transcripts. This observation demonstrates for the first time that MCP-1 is expressed not only in atherosclerotic human arteries but also in symptom free arteries and veins in vivo.
Mol Cell Biochem 1993 Sep 08
PMID:The expression of monocyte chemotactic protein (MCP-1) in human vascular endothelium in vitro and in vivo. 810 90

Ischemia and reperfusion may result in injury to one or more of the cellular components of the heart. In addition to damaging myocytes and their contractile capability, ischemia and reperfusion may inflict early and severe injury on the vasculature which, in turn, may further jeopardize the survival of the myocytes. While ischemia is known to cause progressive injury to endothelium and vascular smooth muscle it now appears that reperfusion can inflict additional, possibly severe, injury on the microcirculation which may compromise the return of normal coronary perfusion. This post-ischemic/reperfusion microvascular incompetence ranges from a transient exacerbation of the increase in vascular resistance initiated during ischemia, to a sustained loss of competent capillaries and eventually to the "no reflow" phenomenon which is characterized by the total inability of the affected tissue to be reperfused. Whereas "no reflow" may be of little importance if it occurs in already infarcted tissue, post-ischemic microvascular incompetence in potentially salvable myocardium could be of considerable significance. Evidence is presented that the vascular endothelium, and its ability to regulate coronary vascular tone, play a central and early role in the pathogenesis of myocardial injury. Mechanisms underlying microvascular injury have been identified and pharmacological strategies now exist for the effective manipulation of this injury--a prospect that is of considerable importance in the light of the widespread use of thrombolytic procedures for the reperfusion of the human myocardium.
J Mol Cell Cardiol 1993 Jul
PMID:The myocardial vasculature during ischemia and reperfusion: a target for injury and protection. 823 Feb 41

Lymphocyte migration out of the blood to inflammatory sites is preceded by the adherence of lymphocytes to the vascular endothelium. This lymphocyte binding is enhanced by cytokine activation of the endothelial cells (EC). Small peritoneal exudate lymphocytes (sPEL) migrate preferentially into cutaneous inflammation and to skin injected with INF gamma, TNF alpha or LPS. These cells adhere also to rat microvascular EC and this adherence correlates well with migratory properties of sPEL. Lymphocyte EC adhesion is in part mediated by the VLA-4 molecule on the lymphocytes. Since differences between microvascular and large vessel EC have been described, we investigated whether sPEL adherence to both types of EC is governed by similar molecular mechanisms. Lymphocyte adhesion was low to unstimulated microvascular EC and augmented by pretreatment of EC with INF gamma, TNF alpha and LPS. In contrast, lymphocyte adhesion to unstimulated large vessel (aortic) EC was higher than to microvascular EC and could not be increased by cytokine or LPS treatment. Anti VLA-4 mAb inhibited the enhanced cytokine stimulated adhesion to microvascular EC without affecting adhesion of sPEL to unstimulated EC. Anti VLA-4 mAb inhibited the high spontaneous adhesion to aortic EC, suggesting that with both EC, adhesion is in part VLA-4 dependent.
J Mol Cell Cardiol 1993 Apr
PMID:Effect of a monoclonal antibody to VLA-4 on lymphocyte adherence to microvascular and aortic endothelial cells. 834 Sep 36


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