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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet adhesion to the subendothelium of the vessel wall and to its collagen component plays a key role in hemostasis, thrombosis, and the development of atherosclerosis. In order to study the mechanisms of platelet adhesion and eventually to inhibit adhesion, it has been necessary to develop methods that measure platelet adhesion quantitatively in vivo and in vitro. In this article, the methods that are used to measure platelet adhesion are reviewed critically with emphasis on their aims, advantages, and disadvantages. The methods that are used to measure platelet adhesion can be divided in five groups: (1) methods that use an aggregometer to measure platelet adhesion to collagen in the presence of EDTA; (2) methods that use binding of radiolabeled collagen, affinity chromatography, or gel filtration; (3) the morphometric method of Baumgartner that measures platelet interaction with the subendothelium of an aorta exposed to flow in an annular perfusion chamber; (4) the quantitative isotopic measurement of platelet adhesion to collagen-coated surfaces and to subendothelium with the rotating probe device of Cazenave; and (5) in vivo platelet adhesion to the subendothelium measured by the morphometric method or with platelets radiolabeled with 51Cr or 111In. With these methods is has been possible to study the factors (Ca2+; VIII: von Willebrand factor; hemodynamic factors: red cells, shear rate; components of the vessel wall) governing platelet adhesion to subendothelium and to collagen. It has also been possible to screen and study drugs inhibiting platelet adhesion, which is the first step in the formation of a thrombus at the site of vascular injury.
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PMID:[In vivo and in vitro methods of studying platelet adhesion to the components of the vascular wall]. 12 39

Inbred Carworth Farms Nelson (CFN) congenitally hyperlipidemic rats had significantly shorter coagulation and prothrombin times and higher levels of coagulation factors, II, V, VII, VIII, and X than did controls. Conversely, congenitally hypolipidemic rats of the same strain had significantly longer coagulation and prothrombin times and lower levels of factors II, V, VII, X and XII and of blood platelets than did controls. A loop-shaped polyethylene cannula was inserted into the aorta to assess the potential for thrombosis. The hyperlipidemic group obstructed this significantly faster and the hypolipidemic group slower than did the controls. Normal CFN rats made hypertensive by unilateral renal artery clip developed hypertension together with significantly elevated serum cholesterol and factor VII and X levels. Rhesus monkeys with diet-induced hyperlipidemia showed shorter prothrombin times and higher factor X levels than did controls on normal diet. By selective breeding, two groups of squirrel monkeys were obtained. Both groups had similar serum cholesterol levels on a normal diet but one group (hyperresponders) showed higher serum cholesterol levels on a cholesterol-containing diet than did the other (hyporesponder) group. Both groups showed significantly elevated levels of factors II, V, VII, IX and X on a cholesterol-containing diet. There was good correlation between the levels of many coagulation factors and serum cholesterol in both rats and monkeys. If thrombosis is important in the genesis of atherosclerosis, these findings could indicate that elevation of plasma lipids may play a role, via the coagulation pathway, in the production of human vascular disease.
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PMID:Hyperlipidemia, hypercoagulability, and accelerated thrombosis: studies in congenitally hyperlipidemic rats and in rats and monkeys with induced hyperlipidemia. 81 75

Most of the linkage of atherosclerosis and thrombosis with estrogens is epidemiologic in origin. Although the effects of estrogens on the mechanisms of hemostasis are wide ranging, many are benign; only a few may account for thrombus formation. Platelet function tests have provided extensive but contradictory data, and interpretation is limited because it is uncertain whether a rise in one or more of these parameters is a primary or secondary effect. The most consistent effects of estrogens on coagulation proteins are elevations of fibrinogen; factors II, VII, IX, X, and XII; protein C; and plasminogen. Although these elevations have been attributed to the estrogenic component in oral contraceptives, the progestogen concentration may also influence these increases. Among other coagulation proteins studied, the following are unaffected by oral contraceptive use: factors V, VIII, and XI; prekallikrein; and high-molecular-weight kininogen. In contrast, protein S values are decreased. The plasma concentration of plasmin inhibitor is unchanged, whereas both proteinase inhibitor and macroglobulin are significantly increased by oral contraceptive use. Cl esterase inhibitor is decreased in women taking oral contraceptives and correlates with the increase in Hageman factor. Antithrombin III is one plasma inhibitor for which a decrease in quantity and activity have been associated with a thrombotic tendency in humans. Although data on estrogen-associated changes in the quantity of antithrombin III have been conflicting, the ability of plasma to inhibit factor Xa is significantly reduced in a dose-dependent manner among pre- and postmenopausal estrogen users.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estrogen-associated thromboembolism. 134 94

Cross-sectional associations between leukocyte count and sociodemographic and cardiovascular risk factors were investigated in 14,679 participants aged 45-64 years in the Atherosclerosis Risk in Communities Study carried out in four US communities in 1986-1989. Leukocyte count was strongly associated with present or past history of cigarette smoking and was higher in males than in females and in white subjects than in black subjects. Among never smokers, no sex differences were evident after adjustment for other risk factors. Race-associated differences were substantially reduced after other factors were taken into account in multivariate analyses. In never smokers, leukocyte count was higher in those who reported poor health, and it was inversely associated with high density lipoprotein cholesterol, forced expiratory volume at 1 second, physical activity, and, among whites, height and socioeconomic indicators. It was directly associated with indices of body weight and body fat, heart rate, blood pressure, hemoglobin, platelet count, uric acid, fasting insulin and glycemia, triglycerides, fibrinogen, antithrombin III, protein C, factors VII and VIII, and von Willebrand factor. The associations of leukocyte count with cardiovascular risk factors may either represent manifestation of subclinical disease or suggest that leukocyte count is part of the causal chain leading to atherosclerosis. Alternatively, the relation of leukocyte count to cardiovascular disease may be confounded by risk factors and thus be noncausal.
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PMID:Leukocyte count correlates in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. 144 16

There have been only limited immunocytochemical studies of the cell composition of the early lesions of human atherosclerosis, and none that incorporate a comprehensive panel of antibodies to various cell types and subsets. The authors thus performed a prospective study of 27 lesions from 16 different individuals ranging in age from 15 to 34 years. These were all lesions that appeared grossly as slightly raised, yellow fatty streaks in the posterior ascending aorta, but on histologic examination had varying degrees of round-cell, spindle-cell, and foam-cell accumulation. Using a panel of antibodies, including monoclonal antibodies specific for smooth muscle cells [HHF35], human macrophages [HAM56], endothelial cells [monoclonal antibodies to F. VIII related antigen], lymphocytes [anti-CD45, anti-CD20, anti-CD45RO, anti-T-cell receptor], it was revealed that the predominant cell type in these early lesions was the smooth muscle cell, including the vast majority of the foam cells, which tended to appear in the deeper regions of the lesions. There were variable numbers of smooth muscle cells and lymphocytes; the latter were exclusively T cells. It is concluded that in atherosclerotic lesions of young adults, which may represent various stages of fatty streak formation and advanced fatty streaks, smooth muscle cell accumulation may be an early event.
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PMID:Human atherosclerosis. III. Immunocytochemical analysis of the cell composition of lesions of young adults. 156 51

Researchers have found that oral contraceptives (OCs) change carbohydrate and lipoprotein metabolism and these changes are like those linked with increased risk of cardiovascular (CV) disease, especially myocardial infarction and stroke. Since CV disease is the major cause of death in US women, it is important that OCs not induce changes in carbohydrate and lipoprotein metabolism. A new progestin, norgestimate, has an advantage over other progestins in that it tends not to induce male traits. This is beneficial because androgenicity is related to atherosclerosis which increases the risk of myocardial infarction. Further studies show that the new combined OC (250 mcg norgestimate/35 mcg ethinyl estradiol) does not influence serum glucose tolerance levels. It also does not affect the physiologic regulating system of prostacyclin, the inhibitor of platelet aggregation, by high density lipoprotein (HDL). In addition, it increases prostacyclin metabolites and HDL which may indeed decrease the risk of occlusive thrombotic vascular diseases. Moreover a study in Germany demonstrates that it causes no changes in fibrinopeptide A,m the anticoagulation factors antithrombin III and protein C, or coagulation promoting factors fibrinogen, factor VII, and the components of VIII. In women, it is absorbed well and metabolized extensively before the body eliminates it. Moreover this new combined OC has an overall Pearl index of 0.25. Studies to data indicate that norgestimate/ethinyl estradiol may be more advantageous than other OC formulations. Yet only long term epidemiologic studies can determine if it can indeed decrease the risk of CV diseases linked with older OCs.
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PMID:Norgestimate: a clinical overview of a new progestin. 160 87

Understanding of the pathogenesis of vascular rejection processes encountered in renal transplants is limited. Although initially and still widely thought to be antibody mediated, it is commonly difficult to demonstrate deposition of immunoglobulin (Ig) in affected arteries. We studied the vascular lesions present in 22 transplanted human kidneys with a panel of antibodies and lectins to evaluate the presence of granulocytes (Leu M1), leukocytes (anti-CD45), B cells (L26), T cells (UCHL-1), monocyte/macrophages (HAM 56), endothelial proliferation (Ulex I factor VIII-related antigen), and smooth muscle proliferation (HHF 35). Active (cellular) vascular rejection showed intimal infiltration of T lymphocytes and monocytes/macrophages (Mac) but not B lymphocytes. Lesions of greater chronicity (reduction in cellularity, increase in intimal stromal matrix) showed progressive diminution of the T cell infiltrate but persistence of Mac accompanied by increased smooth muscle cells. Endothelial alterations were limited to disruption and lifting from supporting stroma by infiltrating inflammatory cells; proliferative changes as detected by increased numbers of cells binding Ulex I were not identified. The cell infiltrates were similar in large (renal artery) and small (interlobular) arteries. Evidence for specific deposition of Ig was not present in cases studied by immunofluorescence studies. These studies suggest vascular rejection is commonly mediated by cellular immune mechanisms and the general supposition equating vascular rejection occurring beyond the peritransplant period with humoral rejection is mistaken. Persistent Mac in chronic lesions may be limited to scavenger functions, but their presence suggests activity in modulating intimal proliferation analogous to current hypotheses for such a role for Mac in atherosclerosis.
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PMID:Immunophenotype of vascular rejection in renal transplants. 169 95

We studied the effects of psychosocial stress (S) and diazepam (D) on plasma lipids, adrenocorticotropin (ACTH), and corticosterone (B) levels of cockerels fed an atherogenic diet (AD) consisting of 2% cholesterol plus 5% cottonseed oil added to plain mash (PM). Seventy-six eight-week-old DeKalb cockerels were randomly assigned to the following groups: I. PM; II. PM + D; III. PM + S; ;IV. PM + S + D; V. AD; VI. AD + D; VII. AD + S and VIII. AD + S + D. S was induced by housing two birds to a cage and pairing them to a different bird daily. D was administered daily by gavage. Plasma ACTH and B levels were analyzed by RIA. Aortic atherosclerosis was grossly graded on a scale of 0-4 and also by gravimetric planimetry. After 10 weeks: 1. S birds had a significantly higher incidence and severity (p less than 0.04) of aortic atherogenesis and elevated ACTH and B levels (p less than 0.001) compared to unstressed PM groups. 2. AD significantly elevated the plasma levels of cholesterol, triglycerides, and the lipoprotein cholesterol that was precipitated by heparin-manganese (LDL-C + VLDL-C), compared to initial and/or PM levels (p less than 0.001). AD birds had a greater incidence and more severe aortic lesions in comparison to PM groups (p less than 0.002). Plasma hormone levels were significantly lower in birds fed AD alone compared to controls and stressed birds. 3. D significantly reduced the severity of aortic atheroma as well as decreased hormone levels in all treated groups (p less than 0.001). Therefore, we conclude that aortic atherosclerosis in cockerels can be induced by S and/or AD, and D can markedly reduce atherogenesis under these conditions. Since both AD and D decreased plasma ACTH and B levels, the anti-atherogenic action of D in these birds does not seem to directly involve these pituitary-adrenocortical hormones.
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PMID:Effects of diazepam, psychosocial stress and dietary cholesterol on pituitary-adrenocortical hormone levels and experimental atherosclerosis. 185 May 93

Blood coagulation in a strain of rabbits designated as Watanabe heritable hyperlipidemic (WHHL) rabbits was examined. The activities of vitamin K-dependent clotting factors, contact factors and clotting factor VIII (F VIII) and the fibrinogen level were significantly higher in WHHL rabbits than in normolipidemic rabbits (all age groups). Values for vitamin K-dependent clotting factor were already higher at 2 months of age. Contact factors and fibrinogen levels increased age after 5 to 8 months. F VIII increased between 5 and 8 months and then decreased. At 2 months of age, WHHL rabbits were divided into two groups. Group A was fed standard rabbit chow and group B standard rabbit chow containing 1% probucol. Probucol prevented the progression of atherosclerosis in group B in the absence of a significant reduction in plasma cholesterol level. F VIII and fibrinogen levels were statistically decreased in all rabbits at all ages in group B (P less than 0.05). These differences in clotting factors between the two groups were most obvious at 8 months (P less than 0.02). We conclude that vitamin K-dependent clotting factors may increase with hyperlipemia and that increases in F VIII and fibrinogen may be closely related to the progression of thromboatherosclerosis.
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PMID:Hypercoagulable state in the Watanabe heritable hyperlipidemic rabbit, an animal model for the progression of atherosclerosis. Effect of probucol on coagulation. 274 87

Factor-VIII-Related antigen (VIII R:Ag) is known to be produced by the blood vessel wall. Noxious stimuli increase endothelial release of VIII R:Ag. It might be expected that the development of vasculitis would be associated with increased levels of VIII R:Ag. To investigate this, eight different groups of subjects were studied: 25 patients with systemic sclerosis, 19 with systemic lupus erythematosus, 15 with rheumatoid arthritis (RA) plus vasculitis, 19 with systemic vasculitis and 14 with atherosclerosis. These groups were compared to 29 patients with primary Raynaud's disease, 15 with RA without vasculitis and 50 controls. Results showed that where there was evidence of vascular disease, then VIII R:Ag was elevated. VIII R:Ag appeared to be a more specific marker for vascular damage than erythrocyte sedimentation rate or C-reactive protein. Longitudinal studies in 11 patients showed good correlation between progression of vascular disease and VIII R:Ag.
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PMID:Vascular damage and factor-VIII-related antigen in the rheumatic diseases. 311 42


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