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

The factors involved in the regulation and control of the human plasma fibrinolytic system at the cellular level are unknown at this time. The physiological regulation of plasmin formation in plasma depends primarily on the nature of the circulating zymogen, plasminogen, the physiological activators formed both in the blood and in the vascular endothelium, and the specific plasmin inhibitors found both in plasma and in certain of the cellular elements of the blood. The biosynthesis of the zymogen must be under genetic control, and the activators are probably released, after thrombus and clot formation, from components involved in the surface-mediated initiation of the coagulation system, and from the vascular endothelium. Activation of plasminogen can occur both in the fluid phase surrounding the thrombus and probably at thrombus surfaces, involving both the fibrin clot and the platelet membrane. The plasmin inhibitors act to control the system in order to prevent proteolytic degradation of important physiologic trace proteins of the coagulation, complement and kallikrein-kinin systems by the enzyme.
Mol Cell Biochem 1978 Aug 16
PMID:The human plasma fibrinolytic system: regulation and control. 15 4

Cultured endothelial cells have been shown to produce insulin-like growth factor-binding proteins (IGFBPs); however, the identity of these BPs has not been defined. We now demonstrate that cultured bovine endothelial cells produce IGFBP2, IGFBP3, and IGFBP4 and have mRNA specific for IGFBP2, -3, -4, -5 and -6. DNA probes for bovine IGFBP2-6 were obtained by polymerase chain reaction (PCR) amplification of cDNA from bovine large vessel pulmonary artery and aortic endothelial cells as well as omental and periaortic fat microvessel cells, using oligonucleotide primers whose sequences were based on the reported cDNA sequences of IGFBP2-6. The PCR-derived probes were labeled with 32P and used for Northern blot analysis of RNAs obtained from the four bovine endothelial cell types. Transcripts corresponding to IGFBP2-6 were found in RNA from large vessel endothelial cells (bovine pulmonary artery and bovine aorta) and microvessel cells (periaortic and omental fat). The PCR-derived probe for IGFBP4 was used to screen a bovine pulmonary artery cDNA library for a full-length bovine IGFBP4 cDNA clone. One positive clone, containing a single EcoRI insert of approximately 2.0 kilobases, was selected for further characterization by DNA sequence analysis. This clone contained an open reading frame encoding a 258-amino acid protein that was 97% identical to human IGFBP4, 268 basepairs of 5'-untranslated region, and a longer 1044 basepairs of 3'-untranslated region. IGFBP4 protein was purified from bovine pulmonary artery-conditioned medium, shown to have N-terminal amino acid sequence DEAIHCPPCSEEKLARCR (identical to human IGFBP4) and to be secreted in glycosylated and nonglycosylated forms. Immunoblots further demonstrated that microvessel cells, at early passage, secrete predominantly IGFBP2 and IGFBP3, while large vessel cells, at early and late passages, secrete IGFBP3 and IGFBP4. Thus, cultured bovine endothelial cells synthesize and secrete IGFBP2, IGFBP3, and IGFBP4 and have mRNA encoding IGFBP2-6. The production of specific IGFBPs by endothelial cells raises the interesting possibility that the vascular endothelium contributes to circulating and tissue levels of specific IGFBPs in vivo.
Mol Endocrinol 1992 Nov
PMID:Endothelial cells express insulin-like growth factor-binding proteins 2 to 6. 128 70

Endothelial cell surfaces play key roles in several important physiological and pathological processes such as blood clotting, angiogenic responses, and inflammation. Here we describe the cloning and characterization of tie, a novel type of human endothelial cell surface receptor tyrosine kinase. The extracellular domain of the predicted tie protein product has an exceptional multidomain structure consisting of a cluster of three epidermal growth factor homology motifs embedded between two immunoglobulinlike loops, which are followed by three fibronectin type III repeats next to the transmembrane region. Additionally, a cDNA form lacking the first of the three epidermal growth factor homology domains was isolated, suggesting that alternative splicing creates different tie-type receptors. Cells transfected with tie cDNA expression vector produce glycosylated polypeptides of 117 kDa which are reactive to antisera raised against the tie carboxy terminus. The tie gene was located in chromosomal region 1p33 to 1p34. Expression of the tie gene appeared to be restricted in some cell lines; large amounts of tie mRNA were detected in endothelial cell lines and in some myeloid leukemia cell lines with erythroid and megakaryoblastoid characteristics. In addition, mRNA in situ studies further indicated the endothelial expression of the tie gene. The tie receptor tyrosine kinase may have evolved for multiple protein-protein interactions, possibly including cell adhesion to the vascular endothelium.
Mol Cell Biol 1992 Apr
PMID:A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains. 131 67

The role of NO-formation induced by accumulated endogenous bradykinin (BK) via local ACE-inhibition with ramiprilat (RT) or by adding BK exogenously was evaluated in cultured bovine aortic endothelial cells (BAEC) and in isolated rat hearts with post-ischaemic reperfusion injuries. Furthermore we used the n-octyl-ester of ramipril (RA-octil) which was shown to have no ACE-inhibitory action. In BAEC, ACE-inhibition by RT (1 x 10(-8)-1 x 10(-6) mol/l) or addition of BK (1 x 10(-8)-1 x 10(-6) mol/l) stimulated the formation of NO and prostacyclin (PGI2) as assessed by endothelial cyclic GMP- and 6-keto-PGF1a formation. Cyclic GMP and PGI2 synthesis was completely suppressed by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 1 x 10(-5) mol/l) and by the B2 kinin receptor antagonist HOE 140 (1 x 10(-7) mol/l). RA-octil (1 x 10(-8)-1 x 10(-4) mol/l) did not affect endothelial cyclic GMP production in BAEC. In isolated working rat hearts subjected to local ischemia with reperfusion both RT (1 x 10(-8) mol/l) and BK (1 x 10(-9) mol/l) reduced the incidence and duration of ventricular fibrillation. In parallel myocardial function (left ventricular pressure, coronary flow) and metabolism (high energy rich phosphates) were improved showing a comparable fingerprint for RT and BK. Addition of L-NNA (1 x 10(-6) mol/l) or HOE 140 (1 x 10(-9) mol/l) abolished these protective effects of RT and BK. As in the BAEC studies RA-octil was without beneficial effects on the isolated ischaemic rat heart. The findings on BAEC show that inhibition of ACE localized on the luminal side of the vascular endothelium results in increased synthesis of NO and prostacyclin by local accumulation of endothelium-derived BK. Similar mechanisms may occur in the ischaemic rat heart leading to cardioprotection.
J Mol Cell Cardiol 1992 Aug
PMID:ACE-inhibition induces NO-formation in cultured bovine endothelial cells and protects isolated ischemic rat hearts. 133 74

Granulocytes play an important role in increasing the infarct size after ischemia and reperfusion by the release of oxygen-derived free radicals (ODFR) and lysosomal enzymes. It has been shown that the number of granulocytes adhering to the vascular endothelium increases after occlusion of the coronary artery, and that the area of myocardial damage can be reduced by preventing granulocyte adherence with monoclonal antibodies directed against adhesion receptors. The underlying mechanism of granulocyte activation under these conditions is not yet known. We have investigated whether granulocytes can be activated directly by reduced oxygen tensions. Granulocytes were suspended in a hypoxic buffer and incubated on fibronectin and gelatin coated microtitre plates at 1-3% ambient oxygen to study their ability to adhere to these matrices. The results showed that the adherence of granulocytes to fibronectin was dependent on the duration of hypoxia. After 30 min of incubation under hypoxia granulocyte adherence increased 1.3 to 1.8 fold compared to the normoxic control. The adherence to fibronectin could be inhibited partially by anti-CD18 antibody, a monoclonal antibody to the common beta chain of a class of extracellular matrix receptors. This direct activation of granulocytes due to hypoxic conditions may have implications for the interaction of these cells with the vascular endothelium in vivo.
Mol Cell Biochem 1992 Oct 21
PMID:Studies on the interaction of leucocytes and the myocardial vasculature. I. Effect of hypoxia on the adherence of blood granulocytes. 136 46

The vascular endothelium can be regarded as a widely distributed organ, interposed between the intravascular and extravascular spaces, with a pluripotent function in the regulation of capillary diameter, vascular homeostasis, lipoprotein metabolism and the vascular response to injury. In the basal physiological state these processes provide a non-thrombotic, non-inflammatory vascular lining preventing uncontrolled inflammation and coagulation. Endothelial cells respond to potential harmful conditions (mechanical stress, anoxia, ischemia and oxidative stress) and a variety of hormones and vasoactive mediators by inducing coagulation and production of inflammatory mediators through the production of 'bioactive' lipids. Although the number of studies in isolated myocardial endothelial cells is limited, from the presumed metabolic analogy with endothelial cells isolated (and cultured) from other organs, one may conclude that the bioactive lipids include oxygenated arachidonate metabolites (eicosanoids) and the platelet activating factor (1--O-alkyl-2-acetyl-sn-glycerol-3-phosphocholine; PAF). All aspects of lipid metabolism, related to the production of eicosanoids and PAF, are present within myocardial endothelial cells. There is uptake and incorporation of fatty acids by endothelial cells and liberation from endogenous triacylglycerol and (membrane) phospholipid stores by (phospho)lipases. Endothelial cells oxidize fatty acids in a carnitine-dependent, mitochondrial, pathway. Endothelial cells actively interact with high density lipoprotein (HDL) and low density lipoprotein (LDL) leading to uptake of cholesterol(esters) that undergo intracellular hydrolysis, and re-esterification to phospho- and neutral lipids, and leaving the LDL-particle modified in a way that makes them bind to the scavenger receptor on macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1992 Oct 21
PMID:Lipid metabolism of myocardial endothelial cells. 148 Jan 46

Osteogenic protein one (hOP-1), a member of the transforming growth factor-beta (TGF-beta) supergenic family, was studied for its anti-ischaemic properties in rats subjected to myocardial ischaemia and reperfusion. Ten minutes after ligation (i.e., just prior to reperfusion) of the left coronary artery, 2 or 20 micrograms/rat recombinant human (hOP-1) or its vehicle, was given intravenously. hOP-1 at 20 micrograms significantly reduced reperfusion injury 24 h later compared to rats receiving only vehicle (i.e., 0.9% NaCl). hOP-1 was also found to preserve rat coronary endothelial function (i.e., release of endothelium-derived relaxing factor, EDRF) in perfused hearts following global ischaemia and reperfusion. Moreover, hOP-1 also significantly inhibited adherence of rat neutrophils to rat vascular endothelium in vitro. Thus, hOP-1 exerts significant anti-ischaemic effects. Some of this cardioprotection may be related to the ability of hOP-1 to preserve endothelial function and inhibit neutrophil adherence to the endothelium.
J Mol Cell Cardiol 1992 Jun
PMID:Anti-ischaemic and endothelial protective actions of recombinant human osteogenic protein (hOP-1). 151 76

The integrins are a family of transmembrane glycoproteins that serve as cell-cell and cell-substratum adhesion molecules and help regulate cellular morphology, differentiation, and proliferation. The integrin repertoire of a cell may therefore influence its behavior under resting conditions or following malignant transformation. For this reason, the distribution of integrins in normal lung tissues was determined using monoclonal antibodies against integrins of the beta 1 (VLA) and beta 3 (cytoadhesin) subfamilies and compared with the distribution in a limited number of lung carcinomas. The integrin subunits that bind to collagen and laminin (alpha 1, alpha 2, alpha 3, and alpha 6) and the alpha subunit, which can pair with beta 1, beta 3, or beta 5 and promote fibronectin, fibrinogen, or vitronectin binding, were the predominant integrins expressed on the major cell types of the lung, i.e., bronchial epithelium, vascular endothelium, and smooth muscle. Strong expression of the alpha 5 beta 1 fibronectin receptor and the beta 3 subunit was restricted to the endothelium of large vessels. Integrin expression by the lung carcinoma cells was somewhat heterogeneous; however, the tumors tended to express fewer integrins than did the normal bronchial epithelium.
Am J Respir Cell Mol Biol 1992 Feb
PMID:Distribution of integrin cell adhesion receptors in normal and malignant lung tissue. 154 Mar 82

Recently discovered endothelin is a powerful vasoconstrictor of vascular smooth muscle in vitro, which also profoundly affects the mechanical function of the heart. An increased level of plasma endothelin in patients with acute myocardial infarction suggests the enhanced release of endothelin from vascular endothelium under pathophysiological conditions of the heart. The reperfusion of ischemic myocardium is associated with the activation of polymorphonuclear leukocytes (PMN) generating oxygen-derived free radicals (OFR), as well as, enhanced responsiveness of myocardial alpha 1-adrenergic receptor. Both OFR and catecholamines are implicated in the modulation of release of endothelium-derived peptides.
J Mol Cell Cardiol 1991 Jun
PMID:Release of endothelin from cultured bovine endothelial cells. 168

We hypothesized that Iloprost, a long-acting prostacyclin analog, would inhibit neutrophil (PMN)-induced lung injury and decrease PMN adherence to vascular endothelium. Human PMNs infused into isolated buffer-perfused rat lungs subsequently stimulated with phorbol myristate acetate (PMA) resulted in lung injury as assessed by the accumulation of [125I]bovine serum albumin (125I-BSA) in lung parenchyma and alveolar lavage fluid. Addition of Iloprost to the lung perfusate, prior to activation of the PMNs, reduced lung injury as assessed by a decrease in the accumulation of 125I-BSA in the lung. This protective effect was not due to the vasodilatory effect of Iloprost. Protection by Iloprost was not linked to a reduction in PMA-induced PMN superoxide production since Iloprost did not reduce the amount of superoxide released into lung perfusate. In vitro, Iloprost caused a dose-dependent inhibition of PMA-stimulated PMN adherence to endothelial cells. Iloprost did not affect the number of Mo1 adhesion molecules constitutively expressed or the number of receptors expressed on the PMNs following PMA. Addition of cAMP or dibutyryl cAMP to the endothelial cells mimicked the effects of Iloprost, diminishing PMA-stimulated PMN adhesion. In separate experiments, addition of the phosphodiesterase inhibitor IBMX to Iloprost resulted in a greater inhibition of PMA-stimulated PMN adherence, while addition of an adenylate cyclase inhibitor, SQ 22,536, or cAMP antibodies with the Iloprost abolished Iloprost's inhibitory effect on PMN adhesion. Thus, Iloprost inhibits PMA-activated PMN-induced lung injury despite continued superoxide production. Iloprost inhibition of PMN adhesion is dependent on cAMP.
Am J Respir Cell Mol Biol 1990 Oct
PMID:Iloprost inhibits neutrophil-induced lung injury and neutrophil adherence to endothelial monolayers. 169 99


1 2 3 4 5 6 7 8 9 10 Next >>