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

In this paper are reported the basal results of a multidisciplinary, multicenter study designed to explore in a population with ischemic disease the relation between hemostatic variables, conventional risk factors and atherothrombotic sequelae. 953 patients less than or equal to 69 yrs with documented coronary, cerebral or peripheral atherosclerotic disease were studied and followed-up for 24 months. Examinations included hemostatic and lipid laboratory assays, arterial Doppler examination, cerebral computerized tomography and nuclear magnetic resonance, exercise electrocardiogram and coronary angiography. Fibrinogen (301.4 +/- 71.52 mg/dl) correlated positively with antithrombin III (r = 0.27) and leukocytes (r = 0.25), negatively with HDL-cholesterol (r = 0.18) and tended to increase with smoking. Heavy smokers had higher leukocyte counts than non-smokers (8.0 +/- 2.0 vs. 7.2 +/- 2.1 x 10(3)/microliters), higher triglycerides (1.87 +/- 1.12 vs. 1.53 +/- 1.35 mmol/l) and lower HDL-cholesterol (0.93 +/- 0.27 vs. 1.00 +/- 0.25 mmol/l). FVII correlated positively with triglycerides (r = 0.16) and protein C (r = 0.45). vWF:Ag (145.4 +/- 70.58%) ad FVII:C (139.7 +/- 59.10%) were positively correlated (r = 0.44). FVIII:C correlated positively with fibrinogen (r = 0.21). Myocardial infarction survivors with associated cerebral and peripheral vascular lesions had higher FVIII:C, FVII, fibronogen and vWF:Ag. These findings suggest that hemostatic factors may enhance and/or mediate the effects of conventional risk factors in atherothrombotic ischemic events.
Atherosclerosis 1991 Oct
PMID:The PLAT Study: a multidisciplinary study of hemostatic function and conventional risk factors in vascular disease patients. 159 Aug 30

The influence of invasive investigations on parameters of hemostasis and fibrinolysis is generally unknown, although this has consequences for the design of prospective studies on the association between those parameters and regression or progression of atherosclerosis. We therefore determined hemostatic and fibrinolytic factors in 12 patients who were admitted to the hospital for coronary angiography (CAG; n = 5) or percutaneous transluminal coronary angioplasty (PTCA; n = 7). Blood samples were drawn under basal circumstances on the day before, the day of and the day after CAG or PTCA. Significant changes occur in the concentrations of platelets and white blood cells, hematocrit (Ht), von Willebrand factor antigen (vWF:ag), antithrombin III-activity (AT III-ag), antithrombin III-antigen (AT III-ant), fibrinogen, plasminogen, alpha2-antiplasmin (alpha2-AP), histidine-rich glycoprotein (HRG), and plasminogen activator inhibitor (PAI)-activity. Mean values of beta-thromboglobulin, platelet factor 4, factor VIII:C, tissue-type plasminogen activator activity (t-PA act) and euglobulin clot lysis time (ECLT) do not differ significantly. After correction for Ht, no significant differences exist between the day before and the day of the procedure; but on the day after CAG and PTCA significant differences occur in white blood cells, factor VIII:C, AT III-ag, alpha2-AP and PAI-act. It is concluded that principally blood samples for investigations on fibrinolysis may be taken on the day before or the day of CAG or PTCA without a loss of quality, if the values are corrected for Ht. Samples taken on the day after the procedure are not useful for such purposes.
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PMID:The influence of coronary angiography and angioplasty on parameters of hemostasis and fibrinolysis. 214 44

Endothelial cells were cultured from human aortas and inferior venae cavae of autopsied subjects ranging in age from infancy to 85 years. Endothelial cells in 32 of more than 100 attempted cultures were pure enough for evaluation. Emerged endothelial cells in primary culture were classified into two types: typical endothelium and variant endothelium. Typical endothelial cells were small, round to polygonal shaped, and were arranged uniformly. Their diameter ranged from 50 to 70 microns. Variant endothelial cells were larger, ranging from 100 to 200 microns in diameter, and giant endothelial cells measuring more than 250 microns in diameter were scattered among them. Variant endothelial cells were usually multinucleated and possessed endothelium-specific markers of vWF and Weibel-Palade bodies. No incorporation of [3H]thymidine was found in the nuclei of cultured variant endothelial cells. Although most cultured endothelial cells were of the typical type, variant endothelial cells were interspersed throughout the culture. The ratio of variant endothelial cells to typical cells correlated well with the severity of atherosclerosis, but less so with aging. The number of variant endothelial cells in cultures from inferior venae cavae was slight and constant throughout all age groups. The presence of multinucleated endothelial cells in in vivo aortas was confirmed by both scanning and transmission electron microscopy. They sometimes existed in colonies in the aortas from elderly subjects with intimal-thickened or advanced atherosclerotic lesions. These results indicate that variant endothelial cells were present in vivo and their ratio in primary culture reflected the in vivo population. It is likely that these cells were formed by adhesion of adjacent typical endothelial cells and that this process was affected more by atherosclerosis than by aging. Although it is not clear if the multinucleated variant cells were formed before the formation of atherosclerotic plaque or after the plaque formation, they will contribute to further development of atherosclerotic lesions, which in turn cause malfunction of the cell membrane. We suggest that there is a cyclic effect of these processes for multiplication of the variant endothelial cells and advancement of atherosclerotic lesions.
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PMID:Atherosclerosis- and age-related multinucleated variant endothelial cells in primary culture from human aorta. 259 78

There is now considerable evidence to suggest that some aspects of early lesion formation and later lesion growth are a reaction to injury. Hemodynamic factors are important in determining the site of injury and may produce injury directly. Injury can lead to atherogenesis in animal models as well as in humans. Superficial injury exposes the subendothelium, allowing platelet adhesion, which at high shear rates is dependent on vWF. Platelet adhesion and degranulation release PDGF, which stimulates smooth muscle cell proliferation, synthetic functions, and vasoconstriction. LDL stimulates smooth muscle cell growth as well as damages endothelium in some experimental systems. Thus, a link is provided between platelet and lipid involvement in atherosclerosis. Direct evidence for a role of platelets in atherogenesis comes from studies in which animals were treated to reduce platelet number or function or in which platelet function is genetically impaired (pigs with von Willebrand's disease). In these models, reduced platelet function is associated with less atherosclerosis. Deeper injury exposes collagen, with subsequent platelet aggregation, thrombin and fibrin generation. The role of reduced production of PGI2 and fibrinolytic agents following severe damage is unknown. Deep injury to the vessel occurs during plaque fissuring, the pathologic process underlying most cases of myocardial infarction, unstable angina, and some cases of sudden death. Angioplasty produces amelioration of many patients' symptoms and is safe. However, acute occlusion occurs occasionally, and restenosis in the first year occurs in some 30 percent of patients treated. Angioplasty damages the arterial wall, with endothelial denudation and intimal and medial splitting. Why does this, and plaque injury, by stimulating platelet deposition, not produce more restenosis? Changes in arterial anatomy are likely to be important: the increase in vessel diameter and in blood flow produce conditions less favorable for thrombotic or arteriosclerotic restenosis.
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PMID:Role of platelets in atherogenesis: relevance to coronary arterial restenosis after angioplasty. 295 94

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

A wide variety of haemostatic variables were measured in healthy male subjects predominantly blood donors residing in Riyadh, the capital city of Saudi Arabia. Subjects were divided according to ethnic origin: Saudi Arabs n = 487, Westerners (Europeans and Americans) n = 300, South East Asians (Koreans and Filipinos) n = 360, and West Africans n = 82. There were no significant differences in prothrombin time, partial thromboplastin time, thrombin time, reptilase time, plasma fibrinogen, antithrombin, plasminogen and platelet count between Saudis, Westerners and Asians. Africans exhibited significantly lower plasma levels of fibrinogen, platelet count and plasminogen than other ethnic groups. Arabs and Africans had higher levels of FVIII:C and vWF:ristocetin cofactor than Westerners. On the other hand, FX was significantly higher in Westerners than in other ethnic groups. Smokers had higher fibrinogen levels than non-smokers. These variations, which could not be related to blood group distribution, physical parameters of height and weight, may be due to genetic and/or dietary habits. In conclusion, this study established the existence of racially determined variations in haemostatic variables, with Black Africans showing changes consistent with a lesser tendency towards atherosclerosis and cardiovascular disease than other ethnic groups. These variations should be taken into account when investigating the haemostatic system in patients.
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PMID:Ethnic variations in the haemostatic system: comparison between Arabs, Westerners (Europeans and Americans), Asians and Africans. 757 95

Recent epidemiological evidence indicates that the hemostatic profile is an important predictor of cardiovascular disease, yet its dietary determinants are not well established. An important question is whether dietary fatty acid intake influences blood levels of coagulation proteins. We examined potential dietary determinants of six hemostatic factors--fibrinogen, factor VII, factor (vWF), protein C, and antithrombin III--in four population-based samples totaling over 15,000 participants, blacks and whites, in the Atherosclerosis Risk in Communities (ARIC) Study. Usual dietary intake was assessed by a food frequency questionnaire. Cross-sectional associations were explored using multiple linear regression analysis, adjusting for gender, race, age, body mass index, smoking status, alcohol use, diabetes, and field center. Dietary intake of n-3 polyunsaturated fatty acids (PUFAs) showed negative associations with fibrinogen, factor VIII, and vWF (blacks and whites) and a positive association with protein C (whites only). Fish intake, the major source of dietary n-3 PUFAs, was similarly related to the hemostatic profile: a 1 serving per day greater fish intake was associated with the following predicted differences (95% confidence interval): fibrinogen, -2.9 mg/dL (-6.3, 0.5); factor VIII, -3.3% (-5.4, -1.3); vWF, -2.7% (-5.2, -0.1) (blacks and whites); and protein C, +0.07 microgram/mL (0.03, 0.11) (whites only). Other nutrients or foods were variably associated with the hemostatic factors. These population-based associations, although cross-sectional, suggest that increases in n-3 PUFA intake from fish may modify the blood levels of several coagulation factors.
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PMID:Associations of fish intake and dietary n-3 polyunsaturated fatty acids with a hypocoagulable profile. The Atherosclerosis Risk in Communities (ARIC) Study. 834 95

Fluid shear stress generated by blood flow on arterial wall may play a role in the process of atherosclerosis, not only affecting the mass transport phenomena that take place in blood, but also by modulation of synthesis and secretion of humoral factors released by vascular endothelium that mediate platelet-vessel wall interactions. The present study was designed to investigate whether shear stress, induced by laminar flow, modulates von Willebrand factor (vWF) release from cultured human umbilical vein endothelial cells (HUVEC) and whether this physical stimulation can affect vWF synthesis. Monolayers of HUVEC were exposed to laminar flow of varying magnitude (from 2 to 12 dynes/cm2) using a cone-and-plate device. The release of vWF in cell supernatant and in extracellular matrix by cells exposed to flow or maintained in static conditions was evaluated by enzyme-linked immunosorbent assay. HUVEC exposed to laminar flow released higher amounts of vWF into the cell supernatant within few hours of exposure and vWF secretion was dependent on shear stress magnitude. vWF released in extracellular matrix was also higher in cell monolayers exposed to shear than in static controls. vWF mRNA expression in HUVEC was not affected by exposure of cells to laminar flow, indicating that shear-induced vWF release reflected enhanced secretion without de novo protein synthesis. Immunofluorescence studies showed that the release of vWF is due to exocytosis from Weibel-Palade bodies, the storage organelles of vWF. These data indicate a novel mechanism by which local hemodynamic shear forces modulate endothelial cell function and may play a role in development of arterial thrombotic events.
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PMID:Fluid shear stress modulates von Willebrand factor release from human vascular endothelium. 926 74

Although the arterial tree is exposed to increased pressure in hypertensive patients, paradoxically, the complications of hypertension (heart attacks, stroke) are mainly thrombotic rather than hemorrhagic. Patients with left ventricular (LV) hypertrophy are at high risk of the complications of hypertension. We performed a cross-sectional study of 178 patients attending a hypertension clinic in a city center teaching hospital, and measured plasma levels of the soluble adhesion molecule P-selectin (associated with platelet activity/function and atherosclerosis), the von Willebrand factor (vWf; a marker of endothelial dysfunction), fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor (PAI, an index of fibrinolysis), lipoprotein(a) (Lp(a), associated with thrombogenesis and atherogenesis) and hemorheological indexes (fibrinogen, hematocrit, plasma viscosity, hemoglobin) in patients with essential hypertension, in whom the LV mass and LV mass index were determined using echocardiography. The 178 patients (86 men, mean age 54 +/- 15 years) were compared with 47 normotensive healthy controls (aged 56 +/- 20 years). Hypertensive patients had higher P-selectin, PAI, vWf, fibrin D-dimer, Lp(a), plasma fibrinogen, and plasma viscosity when compared with controls. Black hypertensive patients had higher Lp(a) levels and LV septal and posterior wall thickness on echocardiography, but lower plasma PAI levels. Patients with LV hypertrophy (defined as a LV mass index > 134 g/m2 in men or > 110 g/m2 in women) had higher plasma fibrinogen compared with those without LV hypertrophy. Systolic blood pressures were significantly correlated to age, plasma viscosity, plasma fibrinogen, and vWf. Diastolic blood pressures were significantly correlated with age and plasma fibrinogen. Fibrinogen levels were correlated with LV mass, LV mass index, left atrial size, plasma viscosity, and vWf. Fibrin D-dimer levels were significantly correlated with vWf and fibrinogen levels. Thus, hypertensive patients have high plasma fibrinogen levels, thrombogenesis, and impaired fibrinolysis (as indicated by high D-dimer and PAI levels, respectively), platelet activation (raised soluble P-selectin), and endothelial dysfunction (high vWF). The high plasma fibrinogen levels were related to blood pressures, LV mass index (and LV hypertrophy), and left atrial size. These abnormalities in hemorheologic factors and markers of thrombogenesis and endothelial function may act synergistically to increase the risk of thrombogenesis and atherosclerosis in hypertensive patients.
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PMID:Relation of endothelium, thrombogenesis, and hemorheology in systemic hypertension to ethnicity and left ventricular hypertrophy. 941 37

The role of hemostatic variables (which promote hemostatic plugs and thrombi) and rheological variables (which affect blood flow) in the pathogenesis of vascular diseases (ischemic heart disease, stroke, and peripheral arterial disease) is reviewed, with emphasis on epidemiological studies. Rheological variables are consistently associated with both prevalent and incident cardiovascular disease. These associations are only partly explained by conventional risk factors. The predictive value of plasma viscosity for cardiovascular events is partly explained by fibrinogen, and partly by lipoproteins. The associations of whole blood viscosity with cardiovascular disease are partly explained by plasma viscosity and partly by hematocrit. White cell count, but not platelet count, predicts ischemic heart disease events. Cigarette smokers have higher levels of rheological variables than non-smokers, these increases are partly or wholly reversible in ex-smokers. Lipoprotein reduction by pravastatin lowers plasma and whole-blood viscosity, which may be one mechanism through which lipid lowering produces an early reduction in cardiovascular events. Data from the Edinburgh Artery Study suggest that viscosity is related both to the extent of atherosclerosis, and to ischemia in the presence of a given degree of atherosclerotic stenoses. Among hemostatic variables, fibrinogen, factor VIII: vWF complex, tpA antigen, and fibrin D-dimer are associated with both prevalent and incident cardiovascular disease. Again, these associations are only partly explained by conventional risk factors They suggest that endothelial disturbance and increased fibrin turnover may play roles in cardiovascular disease. Hemostatic and rheological variables are therefore associated with both prevalent and incident cardiovascular disease, and may be mechanisms through which risk factors such as smoking, hyperlipidemia and infections (including oral infections) promote vascular events.
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PMID:Etiopathogenesis of cardiovascular disease: hemostasis, thrombosis, and vascular medicine. 972 96


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