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)

Lipoprotein(a) (Lp[a]), a highly atherogenic lipoprotein particle, is the prominent apolipoprotein B-containing lipoprotein in the hedgehog (Laplaud PM et al, J Lipid Res 1988;29:1157-1170). In the present work, we studied the consequences of the structural homology between the specific Lp(a) glycoprotein, apoprotein(a), and plasminogen on the generation of plasmin by fibrin-bound tissue-type plasminogen activator. The activation of plasminogen was initiated by adding either native plasma or Lp(a)-free plasma supplemented with the equivalent of 0.25 mg/ml of either purified Lp(a) or albumin to a surface of fibrin prepared on micortitration plates and to which human tissue-type plasminogen activator was specifically bound. With the Lp(a)-free plasma, an increase in the binding and activation of plasminogen as a function of time was observed. In contrast, in the presence of Lp(a) (i.e., native plasma or the reconstituted system), a significant decrease in the binding of plasmin(ogen) (approximately 60%) was obtained. These data indicate that hedgehog Lp(a) interferes with the binding and activation of plasminogen at the fibrin surface and may thereby behave as a factor regulating the extent of fibrin deposition. These results support our previous data indicating that high levels of Lp(a) may have antifibrinolytic effects in humans (Rouy D et al, Arterioscler Thromb 1991;11:629-638), are in agreement with the observation that Lp(a) is a risk factor for atherosclerotic disease, and provide further support to the view of Lp(a) as a link between atherosclerosis and thrombosis.
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PMID:Hedgehog lipoprotein(a) is a modulator of activation of plasminogen at the fibrin surface. An in vitro study. 153 29

The study of immune and fibrinolytic systems in 216 atherosclerosis patients with associated chronic obstructions of the lungs revealed a discrete pattern of activity of plasminogen activator which is low in atherosclerosis in contrast to its elevation in combination of atherosclerosis with pulmonary obstructions. The latter cases manifest E-RFC relative number to be reduced in increased number of EAC-RFC. Growing amount of EA-RFM, elevated blood antithrombin III, activation of plasminogen activator in atherosclerosis coexistence with obstructive pulmonary lesions arrest the development of latent DIC syndrome and progression of atherosclerosis.
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PMID:[Changes in immune and fibrinolytic systems of patients with atherosclerosis and chronic nonspecific pulmonary diseases]. 178 74

This study was aimed at examining the effect of chronic cigarette smoking on a venous occlusion test. Two groups of young healthy men, a control group of 20 non-smoking subjects and a group of 21 smoking subjects having an average consumption of 17.6 packages.day-1.years (SD 8.6) were studied. Venous occlusion performed in smokers did not induce a significant measurable release of von Willebrand factor (vWF). The release of tissue-type plasminogen activator (t-PA) was significantly weaker for the smokers than for the control group (P less than 0.02). An inverse correlation was found between the cumulative parameter of tobacco consumption and the measurable amount of t-PA Ag or vWF Ag released during venous occlusion (r' = -0.994 and r' = -0.889). Cigarette smoking is thus associated with disturbances of the biological response to this venous occlusion test.
Atherosclerosis 1991 Dec
PMID:Venous occlusion and chronic cigarette smoking: dose-dependent decrease in the measurable release of tissue-type plasminogen activator and von Willebrand factor. 178 7

Apoprotein(a), (apo[a]), the specific antigen of lipoprotein(a) (Lp[a]), consists of structural domains (a serine protease unit, kringles 4 and 5) with marked homology to those of the corresponding domains in plasminogen. In this study, we have investigated the impact of this unique structural mimicry on the binding and activation of plasminogen by fibrin-bound tissue-type plasminogen activator at the plasma-fibrin interface. We found that the total amount of plasmin generated on the surface of fibrin was decreased in the presence of high concentrations of Lp(a): 197 +/- 65 fmol in plasmas with greater than 60 mg/dl Lp(a) versus 287 +/- 112 fmol in control plasmas. A similar effect was also apparent in the corresponding euglobulin fractions (554 +/- 169 fmol versus 754 +/- 310 fmol), the latter lacking the plasminogen-binding proteins alpha 2-antiplasmin and histidine-rich glycoprotein, but containing Lp(a). The difference between plasma samples was significant (p less than 0.05) as calculated from the percent decrease in plasmin generated from plasmas with high levels of Lp(a) relative to that generated in the paired controls with low Lp(a) levels. The involvement of Lp(a) was verified in a reconstituted system consisting of normal human plasma supplemented with 100 mg/dl of either purified Lp(a) or low density lipoprotein. Lp(a) produced a decrease of 30% in the generation of plasmin (180 fmol versus 255 fmol in plasma, and 485 fmol versus 705 fmol in the euglobulin fraction). Moreover, using a radiolabeled sheep antibody against human apo(a), we were able to demonstrate the binding of 40 fmol Lp(a) to fibrin during ongoing plasminogen activation. These results indicate that Lp(a) impairs the binding of plasminogen to fibrin and thereby decreases the generation of plasmin by occupying C-terminal lysine residues unveiled on the fibrin surface by plasmin degradation as recently reported (Circulation 1990;82[suppl III]:III-92). In consequence, impairment of fibrinolysis and accumulation of Lp(a) at sites of vascular injury may occur, factors that may be important in the development of atherosclerosis and associated thrombosis.
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PMID:Lipoprotein(a) impairs generation of plasmin by fibrin-bound tissue-type plasminogen activator. In vitro studies in a plasma milieu. 182 91

Accelerated atherosclerosis is a serious complication of chronic renal failure (CRF) treated by peritoneal dialysis. In order to study the pathological mechanisms underlying its development we are using an animal model, namely the C57BL/6J mouse, which develops foam cell-type atherosclerotic lesions after surgical induction of CRF. During atherogenesis, monocyte/macrophages move from the circulation to the blood vessel wall, migrate through the endothelium, imbibe lipid and transform into foam cells. Migration through the endothelium involves proteolysis by plasminogen activator (PA) and uptake of lipids involves hydrolysis of lipoproteins by lipoprotein lipase (LPL). Both of these enzymes are secreted by macrophages. In this paper we report the results of studies on the effect of uremia on the secretion of PA and LPL by macrophages from C57BL/6J mice. The secretion of PA and LPL by macrophages from uremic mice (as defined by BUN levels) was higher than that by cells from control animals. Furthermore, whereas macrophage secretion of PA and LPL was significantly less in normal mice fed a high fat diet than in mice fed rodent chow, it was increased above control levels in uremic animals fed the atherogenic diet. We conclude that increased secretion of PA and LPL by macrophages may contribute to atherogenesis in uremic C57BL/6J mice.
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PMID:Macrophage secretory activity and atherosclerosis during chronic renal failure. 198 12

Defibrotide is a polydeoxyribonucleotide salt that shows antithrombotic activity through a suggested profibrinolytic mechanism. To study the effectiveness of defibrotide in atherosclerosis, we evaluated the fibrinolytic and coagulation behavior in normal subjects and patients with atherosclerotic disease, before and after single or repeated intravenous defibrotide infusion. A significant shortening of the ELT was found in all subjects. However, since neither t-PA increase nor PAI decrease was observed, we suggest that the profibrinolytic response to defibrotide may be due to mechanisms other than t-PA stimulation. Our results provide further evidence for the usefulness of defibrotide antithrombotic prophylaxis in atherosclerosis.
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PMID:Fibrinolytic effects of defibrotide in atherosclerotic patients. 206 62

The physiologic mechanisms that influence plasma levels of von Willebrand factor (vWF) are poorly understood but include race, blood group, age, pregnancy, exercise, and adrenergic and neurohumoral stimuli. Inherited abnormalities in von Willebrand's disease (vWD) are associated with a defect of the vWF gene on chromosome 12, but in some cases, coexistence of impaired response of plasminogen activator and telangiectasia suggests the presence of a regulatory defect or more extensive endothelial perturbation. Three broad types of vWD are recognized; in addition, a platelet-type vWD (pseudo-vWD) is due to an abnormal platelet receptor for vWF. The prevalence of vWD, which is difficult to determine because of variations in severity even within a kindred, is reportedly as high as 1%. In a survey of European patients, the prevalence of treated vWD varied from 4.5 to 24 per million. Preliminary results of an international survey of vWD indicate that about 3% of treated patients have seroconversion to human immunodeficiency virus, 50% of whom have symptoms. Inhibitor of vWF occurs in type III vWD after treatment and is associated with the presence of gene deletions. Acquired vWD may complicate lymphoproliferative and autoimmune disorders, and proteolytic degradation of vWF complicates myeloproliferative disorders. The level of vWF is increased during pregnancy and in vascular and other disorders; it may be involved in the pathogenesis of atherosclerosis. High-molecular-weight multimers of vWF and a cofactor are thought to promote the formation of microthrombi in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. Thus, study of vWD has shed light on pathogenetic mechanisms in a wide range of disorders.
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PMID:von Willebrand factor: clinical features of inherited and acquired disorders. 207 62

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 play a critical role in thromboregulation by virtue of a surface-connected fibrinolytic system. Cultured endothelial cells synthesize and secrete tissue-type plasminogen activator (t-PA) which can bind to at least two discrete sites on the cell surface. These binding sites preserve the catalytic activity of t-PA and protect it from its physiological inhibitor (PAI-1). N-terminal glutamic acid plasminogen (Glu-PLG), the main circulating fibrinolytic zymogen, also interacts specifically with the endothelial cell surface. Binding is associated with a 12-fold increase in catalytic efficiency of plasmin generation by t-PA which may reflect conversion of Glu-PLG to its plasmin-modified form, N-terminal lysine plasminogen (Lys-PLG). Lipoprotein(a) is an atherogenic lipoprotein particle which contains the plasminogen-like apolipoprotein(a) bound to low density lipoprotein. We report here that lipoprotein(a) interferes with endothelial cell fibrinolysis by inhibiting plasminogen binding and hence plasmin generation. In addition, we demonstrate lipoprotein(a) accumulation in atherosclerotic lesions. These findings may provide a link between impaired cell surface fibrinolysis and progressive atherosclerosis.
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PMID:Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. 252 66

In order to carry out a multicenter study aimed at understanding the association of hemostatic factors with atherosclerotic vascular disorders for the Atherosclerosis Risk In Communities (ARIC) Study, we compared a blood collection and processing system developed in our laboratory with the state-of-the-art-procedures. The salient features of our system included the use of a new phlebotomy set for venipuncture, the use of Millipore filters for removing platelet residues in the plasma and the use of a mixture of anticoagulants and antiplatelet agents for inhibiting the in vitro activation of platelets, coagulation and fibrinolytic system. The results derived from systematic evaluations indicate that this newly developed system yields the lowest values of plasma beta TG, PF 4 and FPA when compared with the reported values. The technique also gave reliable values of representative hemostatic measurements such as fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin-III, protein C, tissue-type plasminogen activator, and serum thromboxane B2. Further experiments revealed that the samples withstood temporary storage at -70 degrees C and overnight "shipping" manipulations without significant changes in the hemostatic values. We conclude that the described blood collection and processing system may be a valuable asset for conducting multicenter cooperative clinical trials and epidemiologic studies involving blood collection by multiple field centers or clinics.
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PMID:ARIC hemostasis study--I. Development of a blood collection and processing system suitable for multicenter hemostatic studies. 252 84


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