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)

Human plasma contains a factor capable of stimulating vascular prostacyclin generation even in atherosclerotic vessels with minimal in-vitro capacity for PGI2-synthesis. The activity of this prostacyclin stimulating plasma factor (PSPF) has been reported to be elevated in renal failure and hepatic coma. We are not aware of any data as to whether this PSPF plays a role in maintaining hemostatic balance in patients with peripheral vascular lesions. Therefore, we examined 62 patients with peripheral vascular disease (PVD). This study group was subdivided into normo- and hyperlipemic subjects, patients with and without maturity onset diabetes, and plasma beta-thromboglobulin levels higher and lower than 50 ng/ml. 10 healthy sex and age matched persons served as controls. Vascular prostacyclin formation was studied in vitro after incubation of the patients' plasma and a buffer control with various tissue samples (human femoral artery, rat abdominal and thoracic aorta of healthy and of streptozotocin induced diabetic animals, swine endothelial layer and remaining tissue (media and adventitia) and cultured endothelial (EC) and smooth muscle cells (SMC) of minipig arota. In addition, 6-oxo-PFG1 alpha formation by cultured EC and SMC (minipig aorta source) after incubation with tris HCl-buffer or plasma were estimated by means of specific radioimmunoassays. In general, tissue samples and cells incubated in plasma exhibit a marked increase of in-vitro PGI2-formation as compared to buffer. No difference could be found between PSPF of CHD-patients and healthy controls. Similar findings were obtained using incubated vascular tissue and cultured cells by means of the bioassay and specific RIA, respectively. These findings indicate that the PSPF does not seem to be of any clinical relevance in hemostatic regulation in patients with advanced atherosclerosis.
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PMID:Prostacyclin synthesis stimulating plasma factor in patients with peripheral vascular disease. 295 84

Platelets are believed to play a role in the pathogenesis of atherosclerosis and of the vascular obstruction that causes the acute complications of coronary artery disease. Since specific behavioral patterns appear to be related to the development of coronary artery disease and since emotional stress may predispose an individual to acute cardiovascular ischemia, it was hypothesized that platelet activation by catecholamines might be involved in these events. To study emotional stress, plasma samples were obtained from 61 senior medical residents immediately before they were to speak in public. There were significant increases in the plasma concentrations of the platelet-secreted proteins platelet factor 4 and beta-thromboglobulin and epinephrine and norepinephrine immediately before speaking, which demonstrates that platelet activation and secretion occur in association with this type of emotional stress. Four trials were carried out to study the mechanism for this observed platelet secretion: (1) phenoxybenzamine, (2) propranolol, (3) 650 mg aspirin, and (4) 80 mg aspirin were given several hours before the public speaking engagement. Neither phenoxybenzamine nor propranolol in doses that blocked the hemodynamic effects of alpha 1- and beta 1-adrenergic stimulation modified platelet secretion. Aspirin also did not block platelet secretion, which suggests that platelets were not being stimulated through a cyclooxygenase-dependent pathway. This study provides direct evidence of platelet secretion in vivo in association with emotional stress, and underscores the potential importance of platelet activation and secretion in the acute events that occur in patients with vascular disease.
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PMID:Platelet activation and secretion associated with emotional stress. 298 76

Apolipoprotein B (apoB) release from activated washed human platelets was measured by enzyme-linked immunosorbent assay (ELISA) using monospecific rabbit antibodies to human low density lipoprotein (LDL). Activation of platelets with thrombin, Ca2+-ionophore A23187 or stable analogue of prostaglandin endoperoxides U46619 stimulated release of approximately 20 ng apoB/10(8) platelets. Thrombin-induced apoB release was inhibited by the prostacyclin analogue carbacyclin. Dose-response curves of thrombin stimulation and carbacyclin inhibition of apoB and beta-thromboglobulin (beta-TG) release were very similar. Treatment of platelets with heparin did not remove significant amounts of apoB or affect the subsequent release of apoB induced by thrombin. The results of density gradient ultracentrifugation indicated that most of the apoB was released in the LDL density range. These data suggest that human platelets contain immunoreactive apoB, which can be released during platelet activation.
Atherosclerosis 1986 Sep
PMID:Apolipoprotein B release from activated human platelets. 309 50

The effects of a fish oil supplement on lipid and lipoprotein levels, platelet function, and vital signs were investigated in 31 hypercholesterolemic patients. Thirteen patients took 5 g of encapsulated fish oil per day and 18 patients took 5 g of encapsulated safflower oil "placebo" per day for 28 days. Diet and exercise patterns were kept as constant as possible during the study. The fish oil group had significant increases in several lipid/lipoprotein values at the end of the treatment, including an increase of total cholesterol of 14% (P = 0.0001), LDL of 16% (P = 0.003), HDL of 13% (P = 0.015) and HDL2 of 36% (P = 0.009). The triglyceride level fell 24%, a nonsignificant change (P = 0.217). The ratios of total cholesterol/HDL and LDL/HDL were increased at the end of fish oil treatment, and returned to baseline 30 days after fish oil was stopped. The placebo group had no significant changes in any of the lipid/lipoprotein values. Neither the fish oil nor the placebo group had significant changes in vital signs or platelet function tests (bleeding time, thromboxane B2, platelet factor 4 and beta-thromboglobulin) during the study. These results suggest that fish oil supplements may have an adverse effect on lipid/lipoprotein values in hypercholesterolemic patients.
Atherosclerosis 1988 Mar
PMID:Effects of a fish oil concentrate in patients with hypercholesterolemia. 335 19

The kinetics, in vivo distribution and sites of sequestration of autologous In-111-labelled platelets and other platelet function parameters were studied in ten patients with type IIa or IIb familial hypercholesterolaemia and thrombotic complications of atherosclerosis. The in vitro platelet aggregation response to ADP (P = 0.50) and collagen (P = 0.46); binding of fibrinogen to platelets (P = 0.61); and plasma beta-thromboglobulin levels (P = 0.42) of the patients and normal reference subjects did not differ significantly. The in vivo distribution of In-111-labelled platelets at equilibrium was within normal limits, and at the end of platelet life-span the sequestration pattern of labelled platelets in the reticuloendothelial system was also normal (spleen P = 0.31; liver P = 0.54). There was minimal evidence of in vivo platelet activation: only mean platelet lifespan (MPLS), 195 +/- 57 hours (difference between mean MPLS of patients and controls was 25 hours, with a 95% confidence interval from 23 to 31 hours; P = 0.02); mean platelet platelet turnover, 2298 +/- 824 platelets/microliter/hour (P = 0.005); plasma platelet factor 4 (P = 0.02); and the mean circulating platelet aggregate ratio, 0.8 +/- 0.1 (P = 0.02); differed significantly from normal. These results suggest that abnormalities of platelet function and kinetics observed in type II hyperlipoproteinaemia cannot be ascribed wholly to the hyperlipidaemia, but may be induced by the associated atherosclerosis.
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PMID:Kinetics and in vivo distribution of in-111-labelled platelets and platelet function in familial hypercholesterolaemia. 343 47

Although lipids have received most attention in relation to atherosclerosis, vessel injury also has a role in the development of atherosclerotic lesions. Thrombi that form at sites of injury can be incorporated into the wall, causing thickening, and platelets that adhere to damaged vessel walls release a growth factor (PDGF) that stimulates smooth muscle cell proliferation. The early lesions of atherosclerosis are focal and develop around vessel orifices and branches in relation to the patterns of blood flow and areas of increased permeability and endothelial cell damage. Platelets also contribute to the complications of advanced atherosclerosis caused by occlusive thrombi, thromboembolism, and spasm. The causes of vessel wall injury are not established, although there is evidence pointing to disturbed blood flow, hypertension, antigen--antibody complexes, complement, materials originating from platelets and white blood cells, bacteria, endotoxin, viruses, smoking, dietary lipids, homocystinemia, diabetes, other metabolic disorders, and stress. Platelets do not adhere to intact endothelium, but they adhere to the constituents of the subendothelium, release the contents of their granules (including PDGF), and form thromboxanes. If blood flow is disturbed, platelet--fibrin thrombi can form at sites of injury. Platelet adherence to a damaged wall does not require von Willebrand factor except under conditions of high wall shear. Repeated injury of a vessel wall leads to the development of lipid-rich atherosclerotic lesions, even in normocholesterolemic animals, but these lesions do not form if the experimental animals are made thrombocytopenic before injury is induced. Measurable changes in platelets that are associated with the clinical complications of atherosclerosis include shortened survival, release of granule contents (platelet factor 4, beta-thromboglobulin, thrombospondin), formation of thromboxanes, and decreased buoyant density. "Antiplatelet drugs" such as aspirin are proving to be beneficial in selected groups of patients, such as those with unstable angina. Thromboxane synthetase inhibitors and agents that block the thromboxane receptor on platelets are under investigation. Long term administration of "antiplatelet drugs" to affect the rate of development of atherosclerosis seems neither feasible nor desirable. Modification of dietary and smoking habits and control of hypertension are more likely to be beneficial for most individuals.
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PMID:The role of platelets in the development and complications of atherosclerosis. 351 36

Plasma lipid and lipoprotein pattern and platelet activity were studied in blood samples derived from veins and arteries of 10 healthy male subjects. A significant reduction in plasma high-density lipoprotein (HDL) cholesterol, triglyceride and protein levels, as well as in plasma apolipoprotein A-I, was found when lipoproteins were derived from arterial blood in comparison to venous blood. All other lipoproteins were not significantly changed. Platelet activity measured as plasma beta-thromboglobulin levels and as collagen-induced platelet aggregation and 14C-serotonin release in platelet-rich plasma was markedly elevated when platelets were derived from arterial blood. Since reduced plasma HDL concentration and platelet activation are known risk factors for atherosclerosis, our study may suggest a further explanation for the presence of atherosclerotic lesions in arteries but not in veins.
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PMID:Reduced plasma high-density lipoprotein and increased platelet activity in arterial versus venous blood. 367 Dec 49

The pathogenesis of atherosclerosis, a major cause of age-related mortality, remains poorly understood. Although platelets and their products, including thromboxane A2, may be of importance in this process, little is known about eicosenoid biosynthesis and platelet function with increasing age. In order to address the hypothesis that platelet activation increases with age, we measured various indices of platelet function in a group of apparently healthy individuals over the age of 50 years. The circulating platelet aggregate ratio, plasma beta-thromboglobulin and threshold aggregating concentration of arachidonic acid were similar to those in healthy subjects aged less than 40 years. Although the bleeding time (168 +/- 24 vs 300 +/- 24 seconds) was significantly (p less than 0.001) shorter in the older volunteers this may be unrelated to platelet function and merely reflect age related changes in skin and/or vascular function. To further assess platelet and vascular function in vivo, we measured excretion of the major thromboxane and prostacyclin metabolites in urine, 2,3-donor-thromboxane B2 (Tx-M) and 2,3-dinor-6-keto-PGF1 alpha (PGI-M). Both Tx-M (223 +/- 22 vs 152 +/- 19 pg/mg creatinine; p less than 0.005) and PGI-M (198 +/- 21 vs 121 +/- 13 pg/mg creatinine; p less than 0.005) excretion were significantly higher in the older volunteers. These subtle but significant changes in eicosenoid biosynthesis are consistent with the presence of platelet activation in vivo increasing with age in apparently healthy individuals.
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PMID:Eicosenoid biosynthesis and platelet function with advancing age. 375 55

Platelets may be useful as markers of thromboembolic disease. When labeled with indium 111 they allow external imaging of localized clots. Indium 111 is much superior to chromium 51 for this procedure. Detection of circulating platelet aggregates also appears to be a simple means of determining the presence of thromboembolic disorders. In response to injury or involvement in clotting, platelets release several unique proteins not normally found in the plasma. Therefore, elevated levels of these proteins suggest the presence of such damage. Platelet factor 4 and beta-thromboglobulin are the most widely studied of these proteins, and both can be quantitated by radioimmunoassay. Such assays are now commercially available. Elevated levels have been demonstrated in such diverse disorders as deep venous thrombosis, atherosclerosis and diabetes. However, blood must be drawn with great care to avoid in vitro damage to platelets and false elevation of these markers. All of these procedures are promising at present, but their precise role and value await further study.
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PMID:Platelet markers of thromboembolic disease. 616 74

In order to investigate the relationship between the in vivo platelet activation in diabetes mellitus and the endothelial damage connected with the diabetic micro- and/or macroangiopathy, plasma levels of beta-thromboglobulin (B-TG) and of factor VIII-related antigen (VIII R:Ag) were studied (1) in juvenile-onset (Type I) diabetics without clinical signs of angiopathy (age under 12 years) and (2) in mostly maturity-onset (Type II) diabetics with and without overt angiopathy (age between 14 and 60 years). Normal controls and nondiabetics with atherosclerosis were also studied. Plasma levels of both proteins were found to be elevated in all the groups of diabetic and atherosclerotic patients in comparison with the controls. Highest levels were found in adult diabetics with angiopathy and in atherosclerotics even without diabetes, but values of the diabetic children were also elevated. The data suggest a causal relationship between the vascular damage and the enhanced platelet reactivity in which the former may play the primary role.
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PMID:Plasma levels of beta-thromboglobulin and factor VIII-related antigen in diabetic children and adults. 618 37


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