Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The macrophage scavenger receptor is a trimeric membrane glycoprotein with unusual ligand-binding properties which has been implicated in the development of atherosclerosis. The trimeric structure of the bovine type I scavenger receptor, deduced by complementary DNA cloning, contains three extracellular C-terminal cysteine-rich domains connected to the transmembrane domain by a long fibrous stalk. This stalk structure, composed of an alpha-helical coiled coil and a collagen-like triple helix, has not previously been observed in an integral membrane protein.
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PMID:Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. 230 Feb 4

The interaction of blood platelets with collagen is generally considered to be of primary importance in the arrest of bleeding and to have a role in the pathogenesis of thrombosis and atherosclerosis. Following damage to the vascular endothelium, circulating platelets come into contact with exposed collagen fibrils in the subendothelium and spread along it; this is followed by the secretion of several biologically active substances and by aggregation of platelets. The glycoproteins of the platelet plasma membrane have an important role in the mechanisms underlying these processes. So far, two specific defects of platelet function in patients with a bleeding disorder are known to be associated with a glycoprotein defect and the study of these patients has contributed significantly to present concepts of platelet function. The glycoprotein (GP) IIB-III complex, absent or deleted in the aggregation-defective Glanzmann's thrombasthenia, has been identified as the platelet fibrinogen receptor. GPIb, which is absent in the adhesion-defective Bernard-Soulier syndrome, has been identified as the von Willebrand factor receptor on platelets. We now report a defect of the platelet plasma membrane glycoprotein composition in a patient whose platelets are totally unresponsive to collagen.
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PMID:Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. 293 89

A role of von Willebrand factor-mediated platelet function in porcine atherogenesis is strongly suggested by these studies. This influence of platelet function is probably most important in experimental systems that involve long-term observation and low or moderately elevated levels of serum cholesterol. On the other hand, effects of platelet function on development of atherosclerosis in animals with extremely high serum cholesterol levels are difficult to demonstrate and may be of relatively less importance. These observations are consistent with the results of numbers of recent studies describing the relationship of vascular injury to intimal smooth muscle cell proliferation. There is considerable evidence that lipid-rich intimal lesions occur in hypercholesterolemic animals with no antecedent denudation of endothelium or platelet adherence. It is difficult to ascribe intimal proliferation to platelet effects in this setting. On the other hand, endothelial cells, smooth muscle cells, and monocytes, which are all known to be involved in the atherosclerotic process, can produce mitogenic and chemotactic proteins, including platelet-derived growth factor. Therefore, metabolic aberrations of various kinds, including those initiated by mechanical injury or hypercholesterolemia, may promote proliferation in the vascular wall and resultant lesion development. Data from studies of pigs with vWD suggest a contribution of platelets to this process, but the effects of this contribution are modulated by numbers of variables, most of which are yet to be identified. The control of these multiple variables will be necessary before a clear understanding of the magnitude of the platelet-mediated effects can be gained. This will require carefully defined conditions of hypercholesterolemia, special attention to the immunologic variables and study of properly selected vascular segments under known conditions of flow. This later element will be especially important in the study of vWF-mediated platelet function, since shear forces are a critical determinant of vWF function. Systems that model flow conditions in various segments of the aorta, carotid, and coronary arteries are presently under development for this purpose. Finally, studies examining the molecular basis of vWF-mediated and other platelet functions will probably guide the most productive use of these models. Platelet membrane glycoprotein (GP) receptor Ib and the complex GP IIb and IIIa have been shown in ex vivo studies to be binding sites for vWF molecules.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Porcine von Willebrand disease: implications for the pathophysiology of atherosclerosis and thrombosis. 355 Aug 94

This review concerns our understanding of the molecular basis of platelet function in haemostasis. In particular, we indicate how research into platelet membrane glycoprotein (GP) receptors is yielding vital information on the mechanisms of platelet adhesion and aggregation. These receptors, nearly always complexes of two or more subunits, are now known to belong to distinct gene families, some of which are unique to platelets while others are widely distributed in mammalian tissues. GP Ib-IX complexes are responsible for the high-shear-rate-dependent adhesion of platelets to von Willebrand factor (vWF) exposed within the subendothelium of damaged vessels. Other adhesion receptors include members of the VLA subclass of the integrin family: VLA-2, VLA-5 and VLA-6, which mediate platelet adhesion to collagen, fibronectin and laminin, respectively. Platelet aggregation is initiated by distinct populations of receptors specific for each physiological agonist. Many of these receptors, including the highly important and recently cloned thrombin receptor, have seven transmembrane domains and possess highly selective agonist-binding determinants. Finally, we highlight platelet aggregation and the role of GP IIb-IIIa complexes which, following platelet activation, bind fibrinogen and other adhesive proteins. The latter, through being polyvalent for GP IIb-IIIa, then form the bridges linking adjoining platelets. The 'ligand-binding pocket' of GP IIb-IIIa contains at least three sequences essential for ligand binding; fibrinogen also binds to the activated complex through identified domains, one of which, the Arg-Gly-Asp (RGD) sequence, is also found in vWF and the other adhesive proteins able to support platelet aggregation. Finally, we further describe how these, and other glycoproteins in both surface and internal membrane systems, constitute a complex receptor network capable of translocation and reorganization after platelet activation. In cardiovascular disease, platelets accumulate within arteries whose luminal surface has been modified through atherosclerosis. Recent molecular advances are yielding exciting opportunities for the development of new, and more powerful, drugs acting as specific inhibitors of thrombotic processes.
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PMID:A review of the role of platelet membrane glycoproteins in the platelet-vessel wall interaction. 802 47

Endothelium damage is associated with thrombotic risk in a variety of diseases including atherosclerosis, gram negative sepsis, viral infections and neoplastic disease. Therefore, it appears necessary to find a mean for the clinical investigation for such a damage. Among the markers of these cells, thrombomodulin which is a membrane glycoprotein, seems to be of great interest for this purpose. Actually, thrombomodulin is also found in plasma, following an endothelial lesion. Plasma levels of thrombomodulin are increased in a certain number of pathologies associated with endothelium lesion: atheromatous arterial disease, disseminated intravascular coagulation syndrome and also in systemic lupus erythematosus where the levels of plasma thrombomodulin are related to the severity of the pathology. Moreover, previous in vitro studies confirm the fact that the release of thrombomodulin from the endothelial cell membrane occurs during the course of injury by activated leukocytes or hydrogen peroxide. So, one can suppose a prospective interest in the measurement of plasma thrombomodulin as a diagnostic tool for the approach of endothelium damage.
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PMID:Plasma thrombomodulin: new approach of endothelium damage. 820 13

The membrane glycoprotein CD36 is involved in platelet aggregation, inhibition of angiogenesis, atherosclerosis, and sequestration of malaria-parasitized erythrocytes. In this study, immunoprecipitations with anti-CD36 antibodies were performed to identify proteins that associate with CD36 in the platelet membrane. Platelets were solubilized in 1% Triton X-100, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), Brij 96, or Brij 99, and the proteins that coprecipitated with CD36 were identified by peptide mass spectrometry and Western blotting. The tetraspanin protein CD9 and the integrins alphaII(b)beta3 and alpha6beta1 specifically coprecipitated with CD36 from platelets that were solubilized in CHAPS and Brij 99 but not from platelets that were solubilized in Triton X-100. Only CD9 is coprecipitated with CD36 from platelets that were solubilized in Brij 96. Reciprocal immunoprecipitations with antibodies to CD9, alpha6, alphaIIb, or beta3 from Brij 99-solubilized platelets coprecipitated CD36. Coprecipitation of CD36, CD9, and alpha6beta1 was also observed on platelets from a patient with Glanzmann thrombasthenia, indicating that alphaII(b)beta3 is not required for the other proteins to associate. Colocalization of alpha6 and CD36, of CD9 and CD36, and of alpha6 and CD9 was observed on intact platelets prior to solubilization, using double immunofluorescence microscopy. These data indicate that CD36 associates with CD9 and integrins on human blood platelets. These associated proteins may mediate or participate in some of the diverse biological functions of CD36.
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PMID:CD36 associates with CD9 and integrins on human blood platelets. 1123 9

Thrombomodulin, an endothelial membrane glycoprotein, is an essential part of the protein C anti-coagulant pathway. It may also have a role in the regulation of fibrinolysis. We carried out a cross-sectional study to assess the association of soluble thrombomodulin (sTM) with peripheral artery disease (PAD) in a stratified random sample (n=863) of otherwise healthy black and white participants of the Atherosclerosis Risk in Communities (ARIC) Study. PAD was more common in black than in white participants and associated with classical risk factors in an expected manner; positively with age, smoking, hypertension, diabetes (P=0.05), and LDL-cholesterol, and inversely with HDL-cholesterol. Significant positive associations were observed also with fibrinogen and white blood cell count. Overall, the sTM concentration was not a significant predictor of PAD. The association was, however, modified by the level of factor VIII:C in whites (P=0.002 for the interaction), but not in blacks. Protein C was inversely associated with PAD prevalence (odds ratio 0.33, 95% CI 0.18--0.61, P=0.0004). sTM was inversely associated with plasminogen, but no associations with t-PA, PAI-1, or D-dimer were seen. In conclusion, the present results provide some additional evidence on the role of thrombomodulin-protein C pathway in atherosclerotic disease and support our earlier observation on interaction between sTM and factor VIII:C.
Atherosclerosis 2001 Aug
PMID:Cross-sectional association of soluble thrombomodulin with mild peripheral artery disease; the ARIC study. Atherosclerosis Risk in Communities. 1147 30

Tissue factor, a 47 kDa membrane glycoprotein, lies at the basis of the extrinsic pathway of the coagulation cascade. Interaction of TF with factor VIIa results in the formation of fibrin from fibrinogen, thereby inducing the formation of a blood clot. In addition to this well-established role in blood coagulation, TF is associated with various other physiological processes such as sepsis, inflammation, angiogenesis, metastasis and atherosclerosis. The molecular basis of the latter events is slowly emerging. It has become clear that TF-FVIIa interaction elicits a variety of intracellular signalling events that may be implicated in these actions. These events include the sequential activation of Src-like kinases, MAP kinases, small GTPases and calcium signalling. How this progress in the understanding of TF associated signal transduction may generate answers as to the mechanism through which TF exerts it pleiotropic effects will be focus of this review.
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PMID:The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling? 1262 46

Atherosclerosis is a progressive pathological process based on endothelial dysfunction and chronic inflammation. Monocytes, macrophages, and modified lipoproteins, especially oxidized LDLs (oxLDLs), play a fundamental role in the pathogenesis of atherosclerosis. Monocytes evolve into macrophages in the vascular wall and then accumulate oxLDLs, forming foam cells. OxLDLs are toxic and activate foam cells, stimulate the replication of macrophages and their migration into atherosclerotic plaque, and increase the expression of metaloproteinases. Macrophages bind oxLDLs through many types of receptors, among them scavenger receptors. One of these is CD36, a membrane glycoprotein expressed by endothelial cells, adipocytes, smooth and skeletal muscle cells, cardiomiocytes, platelets, monocytes, and macrophages. CD36 recognizes and binds many ligands, such as oxLDLs, long-chain fatty acids, collagen, thrombospondin 1, apoptotic cells, anionic phospholipids, and Plasmodium falciparum-infected erythrocytes. CD36 is involved in many processes, e.g. inner immune system responses, removal of apoptotic cells and Plasmodium falciparum-infected erythrocytes, and the transport of long-chain fatty acids, and it also mediates collagen and thrombospondin action. Recent reports indicate that CD36 may play a role in the development of atherosclerosis. An animal model revealed that lack of CD36 expression restrains atheroslerosis. Increased expression of CD36 was shown in atheroslerotic plaque and damaged vascular tissue. Contradictory data about the effects of antiatherosclerotic drugs on CD36 expression indicate the necessity for further investigation of the role of CD36 in the development of atherosclerosis.
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PMID:[Scavenger receptor CD36: its expression, regulation, and role in the pathogenesis of atherosclerosis. Part I]. 1655 94

Glucose metabolism disorders are significant risk factors for accelerated atherosclerosis, but the exact pathogenesis of this impact and possible co-factors are not precisely known. On the other hand, only two thirds of all atherosclerosis cases are linked to so-called "classic" risk factors, and numerous studies are conducted to recognize those non-classic risk factors, among which homocysteine and adhesive molecules are the most often mentioned. Recently, the class B scavenger receptor CD36 has become an object of interest. Receptor CD36 is a membrane glycoprotein found on the surface of many cells, such as endothelial cells, cardiomyocytes, dendritic cells, platelets, monocytes, and macrophages. Ligands for receptor CD36 are oxidized LDL particles, long-chain fatty acids, collagens, thrombospondin I, apoptotic cells, and phospholipids. Receptor CD36 plays an important role in various processes, e.g. inner immune system response, apoptotic and necrotic cells removal, transport of fatty acids, and inhibition of neoplastic angiogenesis. Scavenging oxidized LDL particles is one of its most important functions. The most recent studies put forward the participation of receptor CD36 in atherogenesis. Additionally, increased CD36 expression has been described in diabetes mellitus and insulin resistance and in the pathogenesis of diabetic macro- and microangiopathy. Confounding data regarding human hereditary receptor CD36 deficiency as well as still unknown interactions between antidiabetic drugs and CD36 expression suggest the necessity for further studies on the participation of receptor CD36 in the atherogenesis linked with glucometabolic disorders and in the development of diabetes mellitus complications.
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PMID:[The influence of diabetes mellitus and insulin resistance on receptor CD36 expression. Part II. The role of receptor CD36 in the pathomechanism of diabetes complications]. 1655 95


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