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)

A significantly negative correlation was demonstrated between HDL-cholesterol levels of serum and the thromboxane B2 (TXB2) formation in clotted whole blood, whereas a significantly positive correlation was estimated between the LDL cholesterol or apolipoprotein B (apo B) levels and the TXB2 formation in clotted whole blood. Similar relationships were observed between the HDL and apo B serum levels and the thrombin-induced malondialdehyde formation in platelet-rich plasma. The levels of HDL2 cholesterol, total cholesterol, apo A-I and of triglycerides were not significantly correlated with the TXB2 or malondialdehyde formation in both systems. The results in this study support the hypothesis that the TXB2 formation may be modulated by endogenous lipoproteins: high level of LDL stimulates and high level of HDL inhibits the TXB2 formation.
Atherosclerosis 1986 May
PMID:Endogenous lipoproteins modify the thromboxane formation capacity of platelets. 371 15

Large VLDL from subjects with HTG but not normal humans bind with high affinity to both the classic LDL receptor present on all cells and the beta-VLDL receptor of macrophages. Binding of HTG-VLDL to the LDL receptor is mediated by a thrombin-accessible conformation of Apo E that is absent in normal VLDL. Binding of HTG VLDL to the beta-VLDL receptor appears to be mediated by one or more apo B species. We find that thrombin-accessible apo E is required for uptake of HTG-VLDL via the LDL receptor but not by the beta-VLDL receptor. Domains within apo B that are present in native chylomicrons and HTG-VLDL or created in vitro with thrombin appear to be required for binding to the beta-VLDL receptor but not the LDL receptor. Triglyceride-rich lipoproteins could be processed in vivo by thrombin or other proteases for preferential uptake and disposal by the beta-VLDL receptor pathway. This process may be involved in the foam cell accumulation and atherosclerosis associated with some types of hypertriglyceridemia.
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PMID:Interactions of triglyceride-rich lipoproteins with receptors: modulation by thrombin. 378 67

Thrombospondin (TSP) is a multifunctional platelet glycoprotein synthesized by a variety of cells in culture including monocytes and macrophages. We now report that 125I-TSP binds specifically, saturably, and reversibly to mouse peritoneal macrophages and to cells of the monocyte-like human cell line U937 with dissociation constants of 6.7-14.5 X 10(-8) M and 3-4 X 10(5) binding sites per cell. TSP mediates an adhesive interaction between thrombin-stimulated platelets and both U937 cells and human blood monocytes. Using a sensitive rosetting assay, we found that monocytes were not rosetted by resting platelets whereas greater than 90% were rosetted by thrombin-stimulated platelets. Monoclonal and polyclonal anti-TSP antibodies markedly inhibited rosetting as did TSP itself. Neither control antibodies nor heparin, fibronectin, fibrinogen, nor the fibronectin adhesion tetrapeptide Arg-Gly-Asp-Ser inhibited rosetting. TSP may thus serve as a molecular bridge linking activated platelets with monocytes at sites of early vascular injury. Such interaction may be of critical importance in the regulation of thrombosis and the initiation of atherosclerosis.
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PMID:Thrombospondin binds to monocytes-macrophages and mediates platelet-monocyte adhesion. 381 52

In order to further characterize the modulation of the ADP-induced aggregation of gel-filtered human platelets by beta 2-glycoprotein-I (beta 2-G-I), the influence of this glycoprotein upon the serotonin (5-HT) release during aggregation was measured. The following results were obtained: beta 2-G-I completely inhibits the 5-HT release during ADP-induced platelet activation. The inhibition is correlated with the inhibition of the second wave of the ADP-induced aggregation. This effect of beta 2-G-I is not dose-dependent and appears above a threshold concentration of 0.1-0.15 mg/ml in the assay. The specificity of the beta 2-G-I interaction with the ADP-activation is supported by results obtained with collagen or thrombin as aggregating agents. In these cases neither the aggregation nor the release is influenced by the glycoprotein. In respect to the results obtained, beta 2-G-I is a potent candidate to be a modulator of ADP-induced platelet activation in vivo.
Atherosclerosis 1987 Feb
PMID:Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation. 382 75

Mast cell population was studied in rats with experimental atherosclerosis. It has been established that animals kept for 8 months on atherogenic diet revealed marked changes in mast cell population. Predominance of light cells and cell defects were noted. Heparin saturation index was reduced (0.35), as compared to the control (3.9). Stimulation of anticoagulation system by DIP-alpha-thrombin in such animals revealed no heparin in the blood. Mast cell subpopulation was characterized by light cell predominance and low heparin saturation index. The nature of cell degradation remained unchanged. The data obtained indicate the defects in mast cell pool in animals with experimental atherosclerosis.
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PMID:[Mast cell population in rats with experimental atherosclerosis]. 382 23

Thrombin-induced thromboxane (TX) A2 production in whole blood, as reflected by serum TXB2 measurements, has proven to be a simple and reproducible capacity-related index of platelet TXA2 production ex vivo. In the present study we have determined the influence of a number of physiologic variables on serum TXB2 measurements performed by radioimmunoassay in a group of 177 subjects undergoing evaluation for atherosclerosis risk factors. Serum TXB2 averaged 300 +/- 108 ng/ml in the whole group, with a normal distribution. No statistically significant correlation was found between serum TXB2 and the continuous variables examined (age, BMI, blood pressure, cigarettes, serum cholesterol, triglyceride, glucose and wine consumption) except for the number of platelets. Platelet TXB2 production did not differ between men and women (296 +/- 119 vs 302 +/- 100 ng/ml). We conclude that, within the limits of the examined variables, serum TXB2 is an easily measurable and highly reproducible capacity index primarily related to platelet cyclooxygenase and TX-synthase activity, which can be used for monitoring drug- or disease-induced changes of these enzyme activities.
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PMID:Physiologic variables affecting thromboxane B2 production in human whole blood. 398 93

The release and the local activity of plasminogen activator (PA) were studied in isolated perfused dog hearts, without or with intimal injury induced by means of a balloon catheter inserted into the left anterior descending coronary artery (LAD). Thrombin but not DFP-thrombin induced a dose-dependent PA release in doses of 8 to 32 units. ADP 20 or 200 mumol but not ergonovine 20 or 200 micrograms induced a weak PA release. The local PA activity was much lower in the LAD at 1 or 4 weeks after this injury than in the intact LAD. However, the release of PA from the hearts after intimal injury was similar to findings in the intact hearts. We conclude from this study that thrombin plays an important role in regulating the coagulation-fibrinolysis system in endothelial cells and that changes in the properties of the endothelial cells may lead to initiation and enhancement of atherosclerosis.
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PMID:Release of plasminogen activator from isolated perfused dog heart. 403 71

Platelet aggregation and [14C]serotonin release induced by collagen and also by ADP and thrombin were significantly decreased in patients with primary Type V hyperlipoproteinemia. Platelets derived from these patients lost their hyporesponsiveness to thrombin and ADP (but not to collagen) after washings and isolation from their plasma environment. On incubation of platelets derived from normolipidemic controls with plasma derived from patients, platelet aggregation and [14C]serotonin release were lowered by 20% and 30%, respectively. On incubation of these platelets with 100 mg/dl of chylomicron triglyceride, a 40% reduction in both platelet aggregation and [14C]serotonin release was observed. The inhibition of platelet activity was positively correlated with chylomicron concentration up to a concentration of 225 mg/dl by chylomicron triglyceride. In 2 patients, bezafibrate administration (600 mg/day) resulted in marked reduction of plasma triglyceride concentration and a parallel improvement in platelet function. The platelet hyporesponsiveness in patients with Type V hyperlipoproteinemia appears to be a consequence of platelet-chylomicron interaction. This depressed platelet function may be responsible for the absence of overt atherosclerosis noted in these patients.
Atherosclerosis 1985 Aug
PMID:Chylomicrons from patients with type V hyperlipoproteinemia inhibit platelet function. 407 53

A survey of the literature shows that when whole blood clots thrombin is formed and there is a decrease in anti-thrombin III (Anti-Th. III) and an increase in heparin neutralizing activity (HNA) which is probably identical to platelet factor 4 derived from platelets. Many studies of atherosclerosis and of arterial and venous thrombosis using various tests thought to measure Anti-Th. III and HNA report a decrease in Anti-Th. III or an increase in HNA or both. We have measured both in patients with atherosclerosis and survivors of myocardial infarction. The HNA was increased and the serum anti-thrombic activity was decreased relative to controls and there was an inverse correlation between the two measurements. All this evidence suggests that some kind of mild chronic intravascular coagulation may occur in atherosclerosis. These changes could be related to the cause or the result of atherosclerosis.
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PMID:Anti-thormbin III and heparin clotting times in thrombosis and atherosclerosis. 445 34

During platelet aggregation a factor is released which stimulates DNA synthesis in vascular smooth muscle cells. We have examined the capacity of plasma free suspensions of intact rabbit platelets to stimulate DNA synthesis in vascular smooth muscle cells in tissue culture. Platelet-rich plasma was obtained by low-speed centrifugation of citrated blood and passed through sterile columns of sepharose 2B beads. The resultant plasma-free platelet suspension was adjusted to 400,000 platelets/mm3. An aliquot was completely aggregated with thrombin, centrifuged and the supernatant examined for ability to stimulate incorporation of [3H]thyrmidine into DNA by cultured vascular smooth muscle cells. Sonication of an aliquot of platelet suspension released an equivalent amount of this stimulating factor. Another aliquot of platelet suspension of identical volume was added directly to the test smooth muscle cells. Stimulation by intact platelets co-cultured with smooth muscle cells was more than twice as great as that of the thrombin-aggregated supernatant. The latter was not increased by increasing the thrombin concentration nor by increasing the time of exposure. The potency of intact platelets was decreased only slightly by segregating them in Millipore chambers indicating the direct contact was not responsible for its enhancement.
Atherosclerosis 1980 Apr
PMID:Effects of rabbit platelets on vascular smooth muscle cell DNA synthesis. 615 29


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