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)

Vascular endothelial cell dysfunction is linked to hemostatic abnormalities and accelerated atherosclerosis in patients receiving maintenance hemodialysis (HD). The relationships between pre-dialysis plasma levels of immunoreactive thrombomodulin, von Willebrand factor, tissue factor and its inhibitor were studied, and the effects of HD procedure on these endothelial markers were observed. All the markers were higher in 39 HD patients than in 15 healthy controls (p<0.0001). HD treatment resulted in a 50% increase in tissue factor pathway inhibitor (p<0.0001), but did not influence the other markers. This increment directly correlated with the post-dialysis decrease in diastolic (p=0.011) and mean arterial blood pressure (p=0.039), and the surface area of the dialysis membrane (p=0.007). There were no associations between the increase in tissue factor pathway inhibitor and the amount of fluid removed, dose of enoxaparin, or other HD-specific factors. In conclusion, HD is responsible for an increase in plasma tissue pathway factor inhibitor level. The release of tissue factor pathway inhibitor during HD is not only due to heparin injection but also to the contact between blood and artificial dialysis membrane, and to HD-activated hemodynamic forces.
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PMID:Effect of hemodialysis on plasma levels of vascular endothelial markers. 1236 Dec 2

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.
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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.
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PMID:Atherosclerotic and hemostatic abnormalities in patients undergoing hemodialysis. 1264 24

Coagulation activity in KK mice and KK-Ay mice produced by transferring the yellow obese gene (Ay) into KK mice, was studied to examine whether both mice are useful as a model of diabetic atherosclerosis. Plasma levels of hemoglobin A1c (HbA1c), insulin, fibrinogen, plasminogen activator inhibitor (PAI) and thrombomodulin were significantly high in KK and KK-Ay mice compared with age-matched non-diabetic mice (ddY mice). The changes in the plasma levels of fibrinogen at each time-point correlated with the increases in HbA1c levels. Pathological observation by Oil red O staining of aorta tissue from 4-month-old KK and KK-Ay mice revealed the early stages of atherosclerosis such as lipid deposition. These age-related increases in the plasma level of fibrinogen and PAI suggested that KK-Ay mice may contribute to help elucidate the early stages of diabetic atherosclerosis.
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PMID:Increase in plasma fibrinogen and plasminogen activator inhibitor level in diabetic KK and KK-Ay mice. 1265 83

Advanced glycation end products (AGE) are produced by a nonenzymatic reaction between glucose and proteins in the plasma of diabetic patients. Recently, AGE have been reported to promote and accelerate diabetic complications and atherosclerosis. The activity of aldose reductase (AR) is increased in diabetic patients. AGE are reported also to be produced by increased levels of fructose through increased activity of AR in diabetes. Consequently, we administered eparlestat, one of AR inhibitors, to diabetic patients and investigated the plasma carboxymethyl-lysine (CML) concentration, one of the AGE, before and after the administration of eparlestat. Though plasma CML concentration did not show any significant changes in all patients after the administration of eparlestat in the present study (from 2.7 +/- 0.3 mU/mL to 2.5 +/- 0.2 mU/mL; 3 months, 2.9 +/- 0.3 mU/mL; 6 months), plasma CML concentration were significantly decreased 3 months after the administration of eparlestat in the patients whose CML concentration before the treatment was higher than 3 mU/mL (from 3.4 +/- 0.2 mU/mL to 2.6 +/- 0.2 mU/mL; 3 months, p = 0.017). Serum thrombomodulin and HbA1c levels did not show any significant changes. These results suggest that the administration of eparlestat may be beneficial in preventing diabetic complications by decreasing plasma CML in diabetic patients.
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PMID:Effects of eparlestat on plasma levels of advanced glycation end products in patients with type 2 diabetes. 1279 82

The acute coronary syndromes arise from procoagulant changes in complex plaques, which trigger both platelet activation and coagulation pathways. These 2 pathways intersect at a number of points that form positive-feedback loops to sustain and accelerate thrombus formation. In normal hemostasis and with a healthy endothelium, intravascular thrombosis is prevented, and vascular patency is protected by the fibrinolytic system and a number of antithrombotic factors, such as antithrombin, thrombomodulin, and tissue factor pathway inhibitor. However, atherosclerosis is characterized by a hypercoagulable state, and the fibrinolytic balance is skewed toward occlusive thrombus formation at critical sites on vulnerable plaques. This review focuses on cellular and humoral mechanisms and the antithrombotic strategies that are important during the acute phase of an ischemic coronary syndrome, both in patients managed conservatively and in patients scheduled for an interventional procedure. These strategies include fibrinolytic therapy, antiplatelet therapies (aspirin, clopidogrel, glycoprotein IIb/IIIa receptor inhibitors), and low-molecular-weight heparin.
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PMID:Prothrombotic and antithrombotic pathways in acute coronary syndromes. 1281 29

The present study was designed to test the hypothesis that circulating levels of thrombomodulin are elevated in patients with hypertension in proportion to the severity of the vascular damage. A cross-sectional study was carried out using a population consisting of 96 patients with essential hypertension without clinically evident cardiovascular disease (mean age: 65 +/- 10 years) and 99 healthy normotensive control subjects (64 +/- 9 years). Blood was sampled and serum concentrations of soluble thrombomodulin were measured using an enzyme immunoassay method. We calculated the ratio of the concentration of thrombomodulin to that of creatinine, because soluble thrombomodulin is excreted by the kidney and the serum level of thrombomodulin was correlated with that of creatinine (p < 0.05). The association between the ratio and other clinical variables was investigated. The ratio of the thrombomodulin to creatinine concentrations was higher in hypertensive (29.3 +/- 10.9) than in control subjects (24.4 +/- 5.9; p < 0.0001). Systolic blood pressure was correlated with the ratio but the ratio showed no correlation with serum lipid levels when analyzed using data from all subjects. In hypertensive patients, the ratio correlated with the grade of sclerotic, but not hypertensive, changes in the fundus oculi (Scheie's classification, p < 0.001). Furthermore, the ratio correlated with brachial-ankle pulse wave velocity (p < 0.001). However, no correlation was detected between the ratio and blood pressure. These results suggest that circulating levels of thrombomodulin are elevated in hypertensive patients as compared to normotensive subjects and that the thrombomodulin level may be a molecular marker of the latent progression of atherosclerosis in hypertensive patients.
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PMID:Circulating thrombomodulin levels are related to latent progression of atherosclerosis in hypertensive patients. 1286 5

Plasma thrombomodulin (soluble TM; sTM) is considered to be a marker of endothelial injury, but a recent report indicated that the relationship of sTM with thrombosis is complex. Venous thromboembolic events were identified in adults in two longitudinal cohort studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, totaling 21 690 participants. After 8 years of follow-up, sTM was measured in baseline plasma of 305 participants who developed venous thrombosis and 607 who did not. Thrombomodulin A455V genotype was determined in 302 cases and 626 controls. There was no difference in the prevalence of the three TM genotypes between cases and controls and no difference in age-adjusted mean values of sTM by genotype. There were no associations of age-adjusted sTM or TMA455V genotype with overall venous thromboembolism or with thrombosis in any subtype of venous thromboembolism.
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PMID:Prospective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE Study. 1287 44

The damage of the vascular endothelial cells is considered as the primary factor of the development of atherosclerotic changes. The damaged vascular endothelial cells secrete lower amounts of tissue plasminogen activator, antithrombin III, thrombomodulin, endothelium devived relaxing factor (EDRF) prostacycline (PGI2) and glycosaminoglycans. An increase of plasma viscosity and blood procoagulation activity is observed in the peripheral arterial obliterative disease as a result of the interaction between platelets, leucocytes and erythrocytes from the walls of the damaged vessels together with the impairment of blood fibrinolytic activity. It is considered that one of the factors responsible for the development of the atherosclerotic changes is chronic inflammation process of the vascular endothelium. This causes a considerable participation of inflammation cells, i.e. lymphocytes and monocytes in atherosclerosis development. It is observed that an increased level of tissue factor (TF) and factor VII produced as a result of their releasing by the activated monocytes in the atheromatous lamina rupture exerts procoagulation effect. The tissue factor inhibitor inhibits VIIa/TF/Xa complex activity.
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PMID:[Participation of monocytes in the pathogenesis of peripheral arterial obliterating disease]. 1291 11

Recent large clinical trials have demonstrated that HMG-CoA reductase inhibitors, or statins, markedly reduce morbidity and mortality when used in the primary and secondary prevention of cardiovascular disease. It has been established that the benefits of statin therapy in cardiovascular disease can be explained not only by the lipid-lowering potential of statins but also by nonlipid-related mechanisms (so-called "pleiotropic effects") that contribute to the positive effect of statins on the incidence of cardiovascular events. The coagulation and fibrinolytic systems are two separate but reciprocally linked enzyme cascades that regulate the formation and breakdown of fibrin. Numerous studies have demonstrated that disturbances of coagulation and fibrinolysis contribute to the development and progression of atherosclerosis, and that they affect the incidence of atherosclerosis-related clinical events. High plasma levels or activities of fibrinogen, factor VII, factor VIII, von Willebrand factor (vWF), soluble thrombomodulin, tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) are thought to be associated with increased morbidity and mortality related to cardiovascular disease. Experimental studies and many clinical studies have recently shown that statins produce favourable effects on haemostatic parameters, including those that are risk factors for cardiovascular disease. Statins diminish procoagulant activity, which is observed at different stages of the coagulation cascade, including tissue factor (TF) activity, conversion of prothrombin to thrombin and thrombin activity. In some studies, statins also reduced fibrinogen levels. By altering the levels and activities of tPA and PAI-1, statins seem to stimulate fibrinolysis. The data on the effects of combined treatment with statins and other drugs on haemostasis are rather limited. They suggest that statins combined with fibric acid derivatives, omega-3 fatty acids and 17beta-estradiol are superior to statins alone. The only two clinical studies performed in patients with acute coronary syndromes showed a relatively weak effect of statins on haemostasis in those patients. Although various statins may produce different effects on individual variables, there are no convincing data showing that differences in their physicochemical and pharmacokinetic properties significantly alter their net effect on excessive procoagulant activity. Apart from the lipid-lowering effect, statins suppress the synthesis of several important nonsterol isoprenoids derived from the mevalonate pathway, especially farnesyl and geranylgeranyl pyrophosphates, which via enhanced protein prenylation, are involved in the regulation of many cellular processes. It is presumed that the inhibitory effect of statins on the mevalonate pathway is involved in the regulation of some key steps of coagulation and fibrinolysis processes. In this way they probably regulate the synthesis of TF, tPA and PAI-1, and perhaps they also control the generation and activity of thrombin. The beneficial effects of statins on coagulation and fibrinolysis may be responsible for their ability to decrease the number of cardiovascular events. The lipid-independent effects of statins on haemostasis may contribute to the marked decrease in the incidence rates of mortality, hospitalisation and revascularisation in patients treated with these drugs.
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PMID:Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes. 1292 88


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