Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this cross-sectional study was to investigate the relationship between low-grade albuminuria (microalbuminuria) and factors of the coagulation- and fibrinolysis systems in 104 clinically healthy 58-year-old men recruited from the general population. Urinary albumin excretion was significantly associated with body mass index, systolic and diastolic blood pressure, plasminogen activator inhibitor (PAI)-1 activity, tissue plasminogen activator (tPA) antigen, tPA activity (negatively) and protein S (P<0.05). There were no associations between urinary albumin excretion and antithrombin III, fibrinogen, protein C, thrombin/antithrombin factor or von Willebrand factor. In multiple regression analysis urinary albumin excretion was independently and significantly associated with PAI-1 activity and systolic blood pressure (P<0.05). In conclusion we report that urinary albumin excretion was independently and significantly associated with PAI-1 activity in clinically healthy 58-year-old men. This relationship may contribute to the previously reported increased cardiovascular morbidity in subjects with microalbuminuria.
Atherosclerosis 2001 Jul
PMID:Independent relationship between microalbuminuria and plasminogen activator inhibitor-1 activity (PAI-1) activity in clinically healthy 58-year-old men. 1142 21

Thrombomodulin, an endothelial membrane glycoprotein, is an essential part of the protein C anti-coagulant pathway. It may also have a role in the regulation of fibrinolysis. We carried out a cross-sectional study to assess the association of soluble thrombomodulin (sTM) with peripheral artery disease (PAD) in a stratified random sample (n=863) of otherwise healthy black and white participants of the Atherosclerosis Risk in Communities (ARIC) Study. PAD was more common in black than in white participants and associated with classical risk factors in an expected manner; positively with age, smoking, hypertension, diabetes (P=0.05), and LDL-cholesterol, and inversely with HDL-cholesterol. Significant positive associations were observed also with fibrinogen and white blood cell count. Overall, the sTM concentration was not a significant predictor of PAD. The association was, however, modified by the level of factor VIII:C in whites (P=0.002 for the interaction), but not in blacks. Protein C was inversely associated with PAD prevalence (odds ratio 0.33, 95% CI 0.18--0.61, P=0.0004). sTM was inversely associated with plasminogen, but no associations with t-PA, PAI-1, or D-dimer were seen. In conclusion, the present results provide some additional evidence on the role of thrombomodulin-protein C pathway in atherosclerotic disease and support our earlier observation on interaction between sTM and factor VIII:C.
Atherosclerosis 2001 Aug
PMID:Cross-sectional association of soluble thrombomodulin with mild peripheral artery disease; the ARIC study. Atherosclerosis Risk in Communities. 1147 30

Coronary atherosclerosis with occlusive thrombosis is the major cause of acute myocardial infarction. Although plaque rupture is usually hypothesized to be the predisposing event in coronary thrombosis, the possibility cannot be excluded that local changes in the anticoagulant properties of the endothelium overlying the plaque contribute to this process. It is evident that thrombomodulin and the endothelial cell protein C receptor are critical players in the control of the thrombogenic process. This study examined whether thrombomodulin and the endothelial cell protein C receptor are down-regulated on endothelial cells overlying the atherosclerotic plaque in coronary arteries and thus could potentially favor local thrombus formation. Sections of archival left and right coronary arteries (n = 18 each) with severe atherosclerosis from the native heart of six patients who underwent heart transplantation were immunostained for CD31, CD34, endothelial cell protein C receptor, and thrombomodulin using a streptavidin-biotin-peroxidase method. Controls included left and right coronary arteries from autopsy cases with no atherosclerosis (n = 6), and also from cases with mild atherosclerosis (n = 5). The apparent density of all of these proteins was much higher in control than in atherosclerotic arteries. Our findings support the hypothesis that both endothelial cell protein C receptor and thrombomodulin are down-regulated in coronary arteries with atherosclerosis. These changes would be expected to result in reduced inhibition of thrombogenic and anti-inflammatory activity on the endothelium overlying atherosclerotic regions and thus could contribute to coronary thrombosis.
 ...
PMID:Down-regulation of endothelial expression of endothelial cell protein C receptor and thrombomodulin in coronary atherosclerosis. 1154 69

Thrombomodulin is a glycoprotein that can bind to thrombin and activate protein C, thus mitigating the effects of cytokines produced by inflammatory and immunological processes. The molecule exerts a protective function on endothelial cells. Thrombomodulin is cleaved to its soluble form by neutrophil elastase and by other substances produced during acute and chronic inflammatory responses, immunologic reactions and complement activation. ELISA technique yields normal serum levels of 3.1 +/- 1.3 ng/ml; in males these levels are higher; TM levels also rise during menopause. Other circumstances associated with an increase of serum TM levels are smoking, disseminated intravascular coagulation (DIC), cardiac surgery, atherosclerosis, ARDS, liver cirrhosis, diabetes mellitus, cerebral and myocardial infarction, and multiple sclerosis. Serum levels of TM represent an useful prognostic index, because they are associated with an increase in mortality rate, or however a progression of the underlying pathological condition.
 ...
PMID:Clinical importance of thrombomodulin serum levels. 1155 26

We sought to assess the longitudinal stability of risk factors for atherosclerosis and thrombosis. including several coagulation. fibrinolysis, and inflammation factors, in frozen plasma samples stored at -70 degrees C for months or years. We reviewed data collected on 29 different control pools over periods ranging from 7 to 59 months for two functional assays (factor VII and fibrinogen) and seven antigen measurements (C-reactive protein. D-dimer, plasmin-alpha2-antiplasmin complex, plasminogen activator inhibitor-1, protein C, protein S, and tissue plasminogen activator), totaling more than 15,000 data points. Screening of the data using least squares regression revealed only sporadic associations between monthly means and time, with no consistent trends. Analysis by repeated measures and summary measure methods revealed no evidence of sample degradation over time for the factors studied. Our finding of longitudinal stability in the biochemical properties of frozen plasma strengthens the presumption of sample stability on which molecular epidemiologic studies are based.
 ...
PMID:Longitudinal stability of coagulation, fibrinolysis, and inflammation factors in stored plasma samples. 1177 19

Although deficiencies of protein C and antithrombin, 2 natural plasma anticoagulants, are known risk factors for venous thrombosis, population-based prospective incidence data on these associations are lacking. Venous thromboembolic events have been identified in adults in 2 longitudinal cohort studies, the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS). Incidence was examined in relation to prediagnostic plasma levels of protein C (ARIC Study only) and antithrombin. Over a mean of 8.1 years of follow-up, there were 130 incident venous thromboembolic events that were not due to cancer in the ARIC Study. The age-adjusted incidence was elevated 3.36-fold (95% CI 1.24 to 9.11) in the 1.1% of subjects with protein C values <2.0 mg/L compared with subjects with higher values. In contrast, in the ARIC Study and the CHS, there was no association between low plasma antithrombin and venous thromboembolism. In conclusion, in this population-based study, a low protein C, but not antithrombin, level has been determined to be associated with an increased incidence of venous thromboembolism. Attributable risk estimates suggest that low protein C levels account for approximately 2.5% of venous thromboembolic events in the ARIC population.
 ...
PMID:Protein C, antithrombin, and venous thromboembolism incidence: a prospective population-based study. 1206 14

Patients on continuous ambulatory peritoneal dialysis (CAPD) often have abnormalities of lipid metabolism or coagulation and fibrinolysis, these patients may thus be more susceptible to atherosclerosis than those on hemodialysis. It has been reported that hypercoagulability and hyperfibrinolysis are correlated with abnormalities of lipid metabolism. Therefore, we investigated the effect of a decrease in lipids on the coagulation and fibrinolysis system in CAPD patients with hyperlipidemia who received lipid-lowering therapy. The patients included 5 men and 13 women, with a mean age of 52.5 years. Pravastatin sodium (10 mg/day) and ethyl icosapentate (1800 mg/day) were administered concomitantly for 8 weeks. Lipid levels and coagulation/fibrinolysis parameters were measured before and after therapy. The patients were divided into two groups depending on their response to therapy: responders showed a decrease in total cholesterol or triglycerides by at least 20% and non-responders showed less improvement. In the responders, the levels of protein C, tissue plasminogen activator/plasminogen activator inhibitor-I complex, factor XIII, alpha2-plasmin inhibitor, and D-dimer were significantly lower after therapy than before therapy. Protein C, factor XIII, and alpha2-plasmin inhibitor were also significantly decreased after therapy in non-responders, but the extent of the decrease was smaller. The plasminogen level was significantly increased after therapy in non-responders. These findings suggest that a decrease in lipid levels and/or some other action by lipid-lowering agents may correct abnormalities of coagulation and fibrinolysis in CAPD patients.
 ...
PMID:Lipid-lowering therapy and coagulation/fibrinolysis parameters in patients on peritoneal dialysis. 1211 34

Two patients with protein C deficiency who presented with peripheral arterial insufficiency were successfully managed. One patient was managed with bypass surgery for focal gangrene followed by full anticoagulation whilst the other patient was managed with full anticoagulation. Both patients showed characteristic arteriographic findings. Patients who present with peripheral arterial insufficiency demonstrating thrombotic occlusion of main peripheral artery without atherosclerosis and other risk factors should be evaluated for hypercoagulable states.
 ...
PMID:Peripheral arterial insufficiency associated with protein C deficiency. 1238 94

Thromboembolic complications are often seen in patients with nephrotic syndrome. Markers of endothelial cell injury [thrombomodulin, intracellular adhesion molecule, vascular cell adhesion molecule, thrombin activatable fibrinolysis inhibitor (TAFI), protein Z, vascular endothelial growth factor, markers of thrombin and plasmin generation] were studied in 22 patients with nephrotic syndrome. All these parameters studied, except protein Z and D-dimers, were significantly higher in patients with nephrotic syndrome, whereas protein Z was significantly lower when compared with the healthy volunteers. None of the endothelial cell markers (thrombomodulin, P-selectin, E-selectin, intracellular adhesion molecule, vascular cell adhesion molecule), thrombin and plasmin generation markers (thrombin-antithrombin complexes, prothrombin fragments 1 + 2, plasmin-antiplasmin complexes, D-dimers), protein C, protein Z, vascular endothelial growth factor, and TAFI concentration and activity were directly correlated with the level of proteinuria, albumin, cholesterol, triglycerides or creatinine, except significant positive correlations between TAFI activity and serum creatinine, E-selectin and albumin as well as negative correlations between plasmin-antiplasmin complexes and proteinuria. In these patients, there is evidence of endothelial cell injury and probably secondary activation of the coagulation cascade. Elevated circulating TAFI antigen and activity might be a new link in the pathogenesis of impaired fibrinolysis and the progression of atherosclerosis in nephrotic syndrome. Protein Z deficiency might also contribute to the enhanced risk of thromboembolic complications in nephrotic syndrome.
 ...
PMID:Markers of endothelial cell injury and thrombin activatable fibrinolysis inhibitor in nephrotic syndrome. 1243 47

Vascular events caused by atherosclerosis are the major cause of death in patients undergoing hemodialysis (HD). The relationship between the tests of atherosclerosis and hemostasis in 84 patients with HD was examined. Abnormal test results indicting the occurrence of atherosclerosis were found in 66% by the Fontaine score, in 33% by ankle blood pressures, and in 79% by aortic calcification index (ACI). When HD was prolonged, the mean Fontaine score and ACI were further increased. Particularly, the ACI tended to correlate with HD duration. The ankle-brachial index (ABI) was decreased in patients with HD duration of more than 10 years. Before HD, the plasma levels of fibrinogen, plasmin-plasmin inhibitor complex (PIC), thrombomodulin (TM), and D-dimer were increased, while the plasma levels of protein C (PC), antithrombin (AT), thrombin-antithrombin complex (TAT), and tissue plasminogen activator (tPA)-plasminogen activator inhibitor-I (PAI-I) complex (tPA-PAI-1 complex) were decreased. With prolonged HD, the plasma levels of AT and PC were decreased, while those of D-dimer were increased. The plasma levels of TAT and TPA-PAI-1 complex were significantly increased and those of PIC, soluble fibrin (SF) and D-dimer tended to be high in patients with less than 0.7 of ABI. The plasma levels of D-dimer, TPA-PAI-1 complex, TAT, PIC, and SF tended to be high in patients with more than 0.5 in ABI. These findings suggest that patients undergoing HD have progressive atherosclerosis and that this is associated with some hemostatic abnormalities.
 ...
PMID:Atherosclerotic and hemostatic abnormalities in patients undergoing hemodialysis. 1264 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>