Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 adhesion of circulating blood cells to vascular endothelium may be an initial step in atherosclerosis, inflammation, and wound healing. One mechanism for promoting cell-cell adhesion involves the expression of adhesion molecules on the surface of the target cell. Herpes simplex virus infection of endothelium induces arterial injury and has been implicated in the development of human atherosclerosis. We now demonstrate that HSV-infected endothelial cells express the adhesion molecule GMP140 and that this requires cell surface expression of HSV glycoprotein C and local thrombin generation. Monocyte adhesion to HSV-infected endothelial cells was completely inhibited by anti-GMP140 antibodies but not by antibodies to other adhesion molecules such as VCAM and ELAM-1. The induction of GMP140 expression on HSV-infected endothelium may be an important pathophysiological mechanism in virus-induced cell injury and inflammation.
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PMID:Identification of a monocyte receptor on herpesvirus-infected endothelial cells. 171 92

P-selectin (GMP-140) is an adhesion molecule present within endothelial cells that is rapidly translocated to the cell membrane upon activation, where it mediates endothelial-leukocyte interactions. Immunohistochemical analysis of human atherosclerotic plaques has shown strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques. P-selectin is not, however, detected in normal arterial endothelium or in endothelium overlying inactive fibrous plaques. Color image analysis was used to quantitate the degree of P-selectin expression in the endothelium and demonstrates a statistically significant increase in P-selectin expression by atherosclerotic endothelial cells. Double immunofluorescence shows that some of this P-selectin is expressed on the luminal surface of the endothelial cells. Previous work has demonstrated a significant up-regulation in the expression of the intercellular adhesion molecule-1 in atherosclerotic endothelium and a study on the expression of intercellular adhesion molecule-1 and P-selectin in atherosclerosis shows a highly positive correlation. These results suggest that the selective and cooperative expression of P-selectin and intercellular adhesion molecule-1 may be involved in the recruitment of monocytes into sites of atherosclerosis.
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PMID:Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. 751 51

Human blood platelets store an abundance of growth factors, adhensive proteins, coagulation factors, platelet-specific proteins, calcium, serotonin, and adenine nucleotides in their secretory organelles. After exposure to stimuli (thrombin, collagen, ADP, etc.), the platelets undergo a rapid series of morphological change from characteristic disks to spheres with several filopodia, adhension to the inner surface of blood vessels, and aggregation among the platelets. Most of these changes are usually accompanied by secretion or release of dense bodies (release I) and alpha-granules (release II). The secreted products play essential parts in a variety of important physiological and/or pathological events, such as hematosis, thrombosis, blood coagulation, inflammation, and atherosclerosis. Little is known, however, for regulatory mechanism of platelet secretion. Platelets are a distinct kind of cells with many special organelles, but without a nucleus. It also contains a large amount of cytoskeleton. The numerous investigators have suggested that the platelet responses to stimuli are intimately linked to events involving cytoskeleton within the platelets. During platelet activation, as revealed by electron microscopy, the secretory organelles become centralized and enveloped by circular microtubules and a filamentous network. It is implied a possible relationship between cytoskeleton and platelet secretion. However, the precise role of cytoskeleton in platelet secretion remains uncertain. By using exposed GMP-140 (a platelet granule-membrane protein with MW of 140 kDa) as a specific signal of secretion, the present study was designed to investigate the effects of microtubular and microfilamental inhibitors on thrombin-induced platelet secretion.
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PMID:Evidence for thrombin-induced human platelet secretion regulated by the cytoskeleton. 857 6

Circulating levels of the adhesion molecule P-selectin (CD62P) are increased in the plasma of patients with atherosclerosis, but its relationship to the anatomical location of symptomatic disease or extent of symptomatic disease is unknown. The influence of the risk factors for atherosclerosis on soluble P-selectin is also unclear. To clarify these questions we analysed plasma samples from 170 patients with symptomatic peripheral vascular disease and 119 asymptomatic controls who were, as a group, age- and sex-matched. Soluble P-selectin (ELISA) was increased in 83 patients with symptomatic disease of the iliac and/or femoral arteries alone (P < 0.05, ANOVA) but not in 37 patients with symptomatic carotid artery disease alone compared with controls. Soluble P-selectin was equally raised in 120 patients with disease at one arterial site and in 50 patients with disease at two or more arterial sites (both P < 0.05) compared with controls. Smoking and atherosclerosis were both independent predictors of raised soluble P-selectin. We conclude that increased soluble P-selectin may have value as a marker of peripheral vascular disease of the iliac and/or femoral arteries in group comparisons only, as the poor discrimination and wide variation of data make comparisons at the individual level difficult.
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PMID:Soluble P selectin in peripheral vascular disease: relationship to the location and extent of atherosclerotic disease and its risk factors. 903 60

Soluble P-selectin (CD62P) may arise from platelets, the endothelium, or both, and raised levels are found in those with thrombotic disease and atherosclerosis. To determine whether these increased levels in atherosclerosis are related to hypercholesterolaemia, blood samples were obtained from 86 patients (43 with symptomatic vascular disease) attending a hypercholesterolaemia clinic, and 86 age- and sex-matched controls. Parallel measurement of endothelial cell product von Willebrand factor helped define the origin of sP-selectin. Using ELISAs, soluble P-selectin was higher (median 290 ng/ml, range 80-735, P < 0.05) in patients with vascular disease than in both patients with uncomplicated hypercholesterolaemia (median 210 ng/ml, range 55-550), and controls (median 190 ng/ml, range 48-500). Von Willebrand factor was raised in both patients with uncomplicated hypercholesterolaemia (115 +/- 26 IU/dl, P < 0.05) and patients with hypercholesterolaemia and vascular disease (129 +/- 32 IU/dl, P < 0.02) compared with controls (102 +/- 30 IU/dl). Levels of soluble P-selectin did not correlate with von Willebrand factor, total low-density-lipoprotein (LDL) or high-density-lipoprotein (HDL) cholesterol or triglycerides levels, blood pressure or smoking, but von Willebrand factor correlated with LDL cholesterol (r = 0.42, P < 0.05). We conclude that plasma lipoproteins are not a major influence on levels of soluble P-selectin.
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PMID:Soluble P-selectin in hyperlipidaemia with and without symptomatic vascular disease: relationship with von Willebrand factor. 916 22

The physiological meaning of platelets has been best documented for acute coronary syndromes where platelets act as "first responsive elements" triggering the final occlusive thrombus after plaque rupture has occurred. This situation is particularly relevant for patients with NIDDM-type diabetes regularly showing complicated plaque architecture. Predictive power for acute ischemic events e.g. following angioplasty has been proven, and this has dominated the attention exclusively towards the hemostatic function of platelets. Meanwhile, a variety of particularly important platelet features have been identified: a) promotion of liquid phase coagulation; b) regulation of the local vascular tone; c) active modulation of tissue modeling at lesion sites; d) adhesion molecule-mediated communication with a variety of corpuscular blood (and non-blood cells). With emerging recognition of the latter role, the pathophysiological scope of platelets exceeds the well-established role as microemboli, local atherosclerosis amplifiers and triggers of gross thrombosis. In diabetes mellitus of either type, increased populations of circulating platelets have been identified expressing activation dependent adhesion molecules such as activated alpha 2 beta 3 (GPIIbIIIa), lysosomal GP53, thrombospondin or, perhaps most importantly "P-selectin" (CD62 p). This suggests that these adhesion molecules among others can also mediate platelet-leukocyte interactions potentially resulting in inflammatory tissue damaging processes in addition to the immanent tendency towards (micro-)thrombosis. This review works out a more general view on the meaning of platelet activation beyond hemostaseology and updates the actual knowledge of platelet-leukocyte communication checkpoints with particular reference to the diabetic state outlining new pharmacological concepts for intervention.
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PMID:Platelet-leukocyte-cross-talk in diabetes mellitus. 949 1

It is widely accepted that atherosclerosis and thrombus formation are closely associated. Recent progress in the development of molecular markers of blood coagulation and platelet enabled us to estimate even the slight activation of blood coagulation and platelet activation systems. We investigated a contract phase-activate coagulation and factor -inhibitor complex (factor XIa-alpha 1 antitrypsin) and expression of CD62P on platelet surface, a specific antigen on platelet, in patients with coronary arterial diseases. We compared these activation markers after stratifying patients according to the number of significant coronary artery stenoses. Patients with three-vessel disease had significantly increased levels of factor XIa-alpha 1 antitrypsin, fibrinogen, and CD62P expression compared to those in other subgroups. Although it is unknown whether these abnormalities are the cause or the result of the vascular lesion, these findings may be important to understand the pathophysiology underlying atherosclerosis or propagation of the atherosclerotic process itself.
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PMID:[Atherosclerosis and activation of platelet and blood coagulation]. 972 35

Butylated hydroxytoluene (BHT) can inhibit experimental atherosclerosis in animals. Although the agent is an antioxidant, the exact mechanism of the reaction in atherosclerosis is still unknown. To investigate the effects of BHT on expression of P-selectin (PADGEM, GMP-140), intercellular adhesion molecule-1 (ICAM-1) and class II MHC (Ia) antigen, we proposed an experiment on rats. Male rats (n=18 per group) were fed either a normal cholesterol control diet, a normal cholesterol diet containing 0.5% BHT (BD), a high cholesterol diet containing 1.5% cholesterol and 0.1% sodium cholate (CD), or the CD diet containing 0.5% BHT (BCD). Rats were sacrificed after 3 days, and after 1, 2, 4, 10, and 17 weeks of dietary treatment. Although there was no gross or light microscopic atherosclerotic lesions, scanning electron microscopy revealed monocytic adhesion to aortic endothelium and mild endothelial injuries in CD and BCD groups. Immunohistochemically, the addition of BHT to a high cholesterol diet inhibited P-selectin expression but not in ICAM-1 and Ia antigen. These findings suggest that in rats, high cholesterol diets induce expression of ICAM-1, P-selectin and Ia antigen. In addition, the antiatherogenic effect of BHT may play a role in the inhibition of P-selectin.
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PMID:Inhibition of expression of P-selectin by antioxidant in cholesterol-fed rats. 1010 17

CD40 is a 48-kDa phosphorylated transmembrane glycoprotein belonging to the TNF receptor superfamily. CD40 has been demonstrated on a range of cell types, and it has an important role in adaptive immunity and inflammation. CD40 has recently been described on platelets but platelet activation by CD40 has not been described. In the present study, we use flow cytometry and immunoblotting to confirm that platelets constitutively express surface CD40. CD40 mRNA was undetectable, suggesting that the protein is synthesized early in platelet differentiation by megakaryocytes. Ligation of platelet CD40 with recombinant soluble CD40L trimer (sCD40LT) caused increased platelet CD62P expression, alpha-granule and dense granule release, and the classical morphological changes associated with platelet activation. CD40 ligation also caused beta3 integrin activation, although this was not accompanied by platelet aggregation. These actions were abrogated by the CD40L blocking antibody TRAP-1 and the CD40 blocking antibodies M2 and M3, showing that activation was mediated by CD40L binding to platelet CD40. beta3 integrin blockade with eptifibatide had no effect, indicating that outside-in signaling via alphaIIbbeta3 was not contributing to these CD40-mediated effects. CD40 ligation led to enhanced platelet-leukocyte adhesion, which is important in the recruitment of leukocytes to sites of thrombosis or inflammation. Our results support a role for CD40-mediated platelet activation in thrombosis, inflammation, and atherosclerosis.
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PMID:CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation. 1275 Mar 3

Platelet activation plays a crucial role in the pathogenesis of coronary heart disease (CHD), peripheral arterial disease (PAD) and cerebral ischaemia, the three main clinical manifestations of atherosclerosis. Circulating-activated platelets are thought to trigger ischaemic complications after angiography, angioplasty and vascular surgery. We studied activation of circulating thrombocytes in patients with PAD and evaluated the influence on platelet activation of intraarterial digital subtraction angiography (DSA) and percutaneous transluminal angioplasty (PTA) in the area of the lower extremities. Our study included 16 control subjects with PAD (clinical stage IIb according to Fontaine), 25 healthy control subjects and 34 PAD patients (clinical stage IIb according to Fontaine), 14 of whom we examined during DSA, 10 during PTA and 10 which we studied during both interventions. To characterize platelet ex vivo activation, the expression of activation-dependent platelet antigens (CD62 and CD63) was measured using flow cytometry. Platelet sensitization was analysed by an additional in vitro activation. Our results show that angioplasty in peripheral vessels causes activation and presumably slight migration or a reduction in the life span of circulating thrombocytes immediately after the PTA procedure and up to 4 h afterwards. DSA was also found to be associated with platelet activation, sensitization and presumptive minor migration or shortened life span of circulating platelets. Immediately after the intervention, PTA seems to influence platelet migration or shortened lifetime of platelets to a greater extent than DSA. We postulate that this is mainly induced by dilatation. More activated and sensitized thrombocytes circulated in patients with PAD compared to healthy control subjects. This supports our assumption that preactivated platelets are particularly involved in activation, sensitization and migration processes or affected by a reduced life span.
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PMID:Activation of circulating platelets in patients with peripheral arterial disease during digital subtraction angiography and percutaneous transluminal angioplasty. 1267 27


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