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)

Increased levels of various plasma molecules, including C-reactive protein (CRP), and endothelial markers von Willebrand factor (vWF), E-selectin, intercellular adhesion molecule-1 (ICAM-1) and thrombomodulin all predict the development and/or progression of cardiovascular disease. As CRP has been shown to upregulate the expression of adhesion molecules on the surface of human umbilical vein endothelial cells (HUVECs) in vitro, we hypothesized that CRP would induce the release of increased levels of the endothelial markers from HUVECs. Accordingly, recombinant human CRP was added to the culture medium of confluent monolayers of HUVECs at physiological to pathological doses of 1-50 microg/ml for 3-48 h. Markers were measured in supernatants by commercial enzyme-linked immunosorbent assays. We found that increased release of thrombomodulin was induced by 20 and 50 microg/ml CRP after 48 h. Increased ICAM-1 was induced by 50 microg/ml CRP after 24 and 48 h. There was no clear influence of CRP on E-selectin, but 20 and 50 microg/ml CRP inhibited the release of vWF. Our data provide further evidence of a link between increased levels of ICAM-1, thrombomodulin and CRP in atherosclerosis, but they counter reports of a direct, possibly causal, relationship between CRP and increases in E-selectin or vWF.
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PMID:Effects of C-reactive protein on the release of von Willebrand factor, E-selectin, thrombomodulin and intercellular adhesion molecule-1 from human umbilical vein endothelial cells. 1294 74

Expression of thrombomodulin (TM) in atherosclerotic lesions of the human aorta (8 cases of diffuse intimal thickening, 4 fatty streaks, 11 atheromatous plaques, and 5 fibrous plaques) as well as in undiseased aortas of 5 infants obtained at autopsy was studied immunohistochemically using a novel polyclonal antibody against human TM. TM was expressed in intimal smooth muscle cells (SMC) besides endothelial cells and foamy macrophages in almost all patients (26/28). In addition, medial SMC in adult cases over 27 years of age expressed TM. In young adults with diffuse intimal thickening under 26 years of age, medial SMC showed no TM expression whereas intimal SMC did show it. Both intimal and medial SMC in infants showed no TM expression. An immunofluorescence method showed TM expression in cultured adult human SMC. These findings indicate that TM expression in SMC may depend on patient age as well as lesion type of atherosclerosis.
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PMID:Expression of thrombomodulin in human aortic smooth muscle cells with special reference to atherosclerotic lesion types and age differences. 1450 60

Kidney transplant recipients are not only prone to dyslipidemia but also have a high risk of cardiovascular death. Impairment of the fibrinolytic system is thought to be one factor playing a role in development of thrombotic complications. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a glycoprotein, linking coagulation and fibrinolysis. The purpose of this study was to assess TAFI concentrations and activities in renal transplant recipients stratified based upon serum cholesterol values above 220 mg/dL or below 200 mg/dL. The groups did not differ regarding age, creatinine clearance, BMI, time after transplantation, albumin, fibrinogen, thrombomodulin, or PAP. Additionally, we evaluated thrombin activity (thrombin-antithrombin complex TAT, prothrombin fragments 1 + 2); TAFI activator; thrombomodulin (TM), catalyzer of TAFI activation; and the degree of plasmin generation (plasmin-antiplasmin complex PAP) using commercially available kits. In patients with hyperlipidemia significantly higher TAFI concentrations and activities may contribute to prolonged ECLT and lowered fibrinolytic activity index (FAI). Increased levels of F1 + 2 and TAT were observed in hypercholesterolemic patients, indicating enhanced thrombin generation. Elevated TAFI concentration, and activities and enhanced thrombin generation observed in hypercholesterolemic kidney transplant recipients may contribute to hypofibrinolysis and progression of atherosclerosis in this group of patients.
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PMID:Thrombin-activatable fibrinolysis inhibitor in kidney transplant recipient with dyslipidemia. 1452 94

Many risk factors for cardiovascular disease generate superoxide in the blood vessels and thereby impair endothelial function. To emphasize the critical role of oxygen radicals, this is a 'radical view' of those risk factors. It will be useful to organize risk factors into a 'superfamily', with consideration of mediators, mechanisms, and target organs. Studies are summarized which suggest that, in parallel with the impairment of endothelial vasomotor function, the thrombin/thrombomodulin/activated protein C anticoagulant mechanism, which requires endothelial thrombomodulin, is also impaired by atherosclerosis and improves during regression of atherosclerosis. Impairment of the anticoagulant mechanism may contribute to thrombosis in atherosclerotic arteries, and improvement of the anticoagulant mechanism during regression of atherosclerosis may reduce the risk of cardiovascular events.
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PMID:Mikamo Lecture: a radical view on the 'superfamily' of cardiovascular risk factors. 1457 9

Plasma levels of C-reactive protein (CRP) and serum amyloid A protein (SAA), inflammatory markers, and soluble thrombomodulin (s-TM), a marker of endothelial damage. are thought to be related to coronary artery disease. However, the relationship between these inflammatory markers and endothelial injury in atherosclerotic coronary arteries is still unclear. Fifty-five patients who underwent coronary angiography were classified into 3 groups according to the severity of left coronary arterial atherosclerosis evaluated by the Gensini score (GS; normal: score = 0, n = 15; mild: 0 < score < 15, n = 29; severe: score > or = 15, n = 11). Blood samples were obtained from the aortic root (Ao) and coronary sinus (CS) and plasma CRP and SAA levels were measured by latex turbidimetric immunoassays, and s-TM levels were determined by an enzyme-linked immunosorbent assay. The difference between marker concentrations in the Ao and CS of the coronary circulation was expressed as the coronary sino-arterial (CS-Ao) difference. The CS-Ao differences of s-TM and SAA were significantly higher in patients with severe atherosclerosis than in normal patients (P < 0.01), and showed weak but significant positive correlations with the GS (r = 0.34, P < 0.01 and r = 0.33, P < 0.05, respectively). The CS-Ao differences in CRP did not differ among the three groups, and did not correlate with the GS. The results of our study reveal a possible relationship between endothelial cell injury and inflammation in atherosclerotic coronary arteries.
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PMID:Plasma levels of soluble thrombomodulin, C-reactive protein, and serum amyloid A protein in the atherosclerotic coronary circulation. 1458 42

In type 2 diabetic patients with or without nephropathy, we examined relationships between plasma concentrations of total homocysteine (tHcy) and clinical macroangiopathy, as well as endothelial dysfunction indicated by plasma thrombomodulin (TM) concentrations. We studied 103 type 2 diabetic patients including 26 with macroangiopathy (12 patients with coronary artery disease [CAD], 10 with stroke, and 4 with peripheral vascular disease [PVD]). Plasma tHcy was measured by high-performance liquid chromatography. Plasma TM was determined by enzyme immunoassay. As an index of glomerular filtration rate, creatinine clearance (Ccr) also was determined in a 24-hour urine collection. Considering all diabetic patients, plasma tHcy concentrations were significantly higher in those with macroangiopathy than in those without (10.4 +/- 3.7 v 8.5 +/- 2.8 micromol/L, P=.0077). By univariate and multivariate analyses, plasma tHcy was correlated inversely with Ccr. Plasma tHcy concentrations were significantly higher in the patients with overt albuminuria than in those with normoalbuminuria or microalbuminuria. After exclusion of patients with renal insufficiency (Ccr<60 mL/min), differences in plasma tHcy concentrations between patients with and without macroangiopathy were abolished. By multivariate analysis, total cholesterol, urinary albumin, Ccr, C-peptide, and tHcy retained significant influence on the plasma TM. Even in patients with normal renal function (Ccr > or = 80 mL/min), plasma tHcy was correlated positively with plasma TM. In conclusions, diabetic nephropathy is a main determinant of plasma tHcy elevation in type 2 diabetic patients. Since plasma TM is independently associated with plasma tHcy, in diabetic patients with overt nephropathy, elevation of tHcy reflecting reduced clearance is a likely cause of endothelial dysfunction, resulting in the atherosclerosis underlying development of cardiovascular disease.
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PMID:High plasma homocysteine concentrations are associated with plasma concentrations of thrombomodulin in patients with type 2 diabetes and link diabetic nephropathy to macroangiopathy. 1462 17

Recent studies have suggested that leptin, a plasma protein secreted by adipocytes, may play a role in artherothrombosis. In this study, we tested the hypothesis that leptin contributes to in vivo endothelial dysfunction in obese subjects. A cross-sectional comparison of plasma leptin, soluble thrombomodulin (sTM) and soluble vascular adhesion molecule-1 (VCAM-1) was carried out in 35 obese women (age 48+/-13) selected with a body mass index (BMI) > or =30kg/m(2) and 25 normal weight women (age 50+/-11, BMI < 25). An additional study was conducted to determine the short-term effects of weight loss induced by caloric restriction. Plasma levels of leptin, sTM and sVCAM-1 were measured before and after weight loss. Obese women had higher levels of leptin (35+/-22 versus 22+/-19, P<0.01), sTM (4.8+/-1.8 versus 1.9+/-1.5, P<0.001) and sVCAM-1 (726+/-109 versus 583+/-50, P<0.001) than non-obese women. sTM and sVCAM-1 concentrations had a positive correlation with BMI (sTM, r=0.70, P<0.001; sVCAM-1, r=0.60, P<0.001), waist circumference (sTM, r=0.66, P<0.001; sVCAM-1, r=0.37, P<0.01) and leptin levels (sTM, r=0.53, P<0.001; sVCAM-1, r=0.42, P<0.005). At multiple regression analysis leptin predicted sTM and sVCAM-1 independently of obesity measures and other covariates. Twenty-nine obese patients who completed the program of weight reduction showed a significant decrease in leptin, sTM, and sVCAM-1 levels. The magnitude of decrease of sTM and sVCAM-1 was related to the magnitude of reduction in leptin levels. Therefore, our results show that obesity is associated with enhanced levels of atherosclerosis markers. These abnormalities are related to abdominal obesity possibly mediated by leptin levels, and are reversible with weight loss.
Atherosclerosis 2004 Jan
PMID:Soluble thrombomodulin and vascular adhesion molecule-1 are associated to leptin plasma levels in obese women. 1470 73

Endothelial dysfunction with atherosclerosis is a recognized complication of uremic patients. The hypoalbuminemia of peritoneal dialysis (PD) patients can induce a hypercoagulable and atherogenic state. In this study, we investigated the role played by malnutrition-inflammation syndrome on endothelial function markers in PD patients. We measured markers of nutrition [normalized protein catabolic rate (nPCR), albumin, prealbumin, insulin-like growth factor 1 (IGF-1), transferrin, and cholesterol], markers of endothelial damage and function [tissue-type plasminogen activator (tPA), thrombomodulin (TM), von Willebrand factor (vWF), and NO3 (representing NO)], markers of a coagulable state [fibrinogen and plasminogen activator inhibitor 1 (PAI-1)], markers of inflammation [tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP)], and other endothelial injury factors [lipoprotein(a) [Lp(a)] and homocysteine]. We also performed an endothelial stimulation test consisting of right-arm venous occlusion (VO) for 10 minutes. The patients were divided into four groups according to their clinical atherosclerotic score (CAS). We studied 45 clinically stable PD patients. At baseline, statistically significant negative linear correlations were found between albumin and age (r = -0.54, p < 0.05), albumin and vWF post-VO (r = -0.54, p < 0.05), and albumin and TM (r = -0.36, p < 0.05), which are endothelial damage markers and prothrombotic factors. A positive linear correlation was seen between albumin and NO3 post-VO (r = 0.48, p < 0.05), indicating a high vasodilatation capacity. C-Reactive protein and TNF alpha showed a positive linear correlation (r = 0.5, p < 0.01). Similarly, TNF alpha showed a positive linear correlation with cardiovascular risk markers such as fibrinogen (r = 0.79, p < 0.01), PAI-1 (r = 0.44, p < 0.05), and homocysteine (r = 0.37, p < 0.05). Creatinine clearance showed a negative linear correlation with TM (r = -0.36, p < 0.05). Patients with albumin < 4 g/dL showed a lower tPA ratio, lower NO3, and a higher CRP, TNF alpha, and Lp(a) than did patients with albumin > 4 g/dL [tPA ratio: 2.1 +/- 1.56 (n = 29) vs. 2.6 +/- 2.3 (n = 16), p < 0.05; NO3: 47 +/- 27 micrograms/mL vs. 69 +/- 33 micrograms/mL, p < 0.05; CRP: 1.8 +/- 3 mg/dL vs. 1.1 +/- 1.6 mg/dL, p < 0.05; TNF alpha: 44.4 +/- 16 pg/mL vs. 36.6 +/- 21.4 pg/mL, p < 0.05; Lp(a): 55 +/- 39 mg/dL vs. 33 +/- 21 mg/dL, p < 0.05]. Patients with a worse CAS showed higher homocysteine levels and lower albumin values. Those relationships were maintained in both periods of the study. We found no relationships between dialysis dose and endothelial function markers. In conclusion, malnutrition-inflammation syndrome may contribute to endothelial dysfunction and, consequently, to prothrombotic and proatherogenic processes in PD patients.
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PMID:Malnutrition-inflammation syndrome is associated with endothelial dysfunction in peritoneal dialysis patients. 1476 71

Hypercoagulability is a risk factor for atherosclerosis (As) and plays an important role in the development of As. Hypercoagulability results from mutation and unusual expression of clotting system-related genes, anticlotting system-related genes, fibrinolytic system-related genes and other related genes. Factor V gene, prothrombin gene and tissue factor gene in clotting system, thrombomodulin gene and antithrombin III in anticlotting system, plasminogen activator inhibitor-1 gene in fibrinolytic system, are related with hypercoagulability tightly.
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PMID:[Mutation and unusual expression of clotting system-related genes and hypercoagulability]. 1499 14

Oxidant stress is a well known cause of damage in the atherosclerotic process. Vitamin E is one of the most promising natural antioxidants. In this study we investigated if a vitamin E-coated dialyzer was able to reduce the plasma levels of auto-antibodies against oxidized-LDL, von Willebrand factor (vWf) and thrombomodulin (TM) as markers of endothelial damage. In this controlled 6-month prospective study, we investigated these markers in two matched groups (n=16 each) of patients on regular hemodialysis not yet diagnosed for atherosclerosis cardiovascular disease (ACVD) (mean age=58.3+/-7.0 yrs, mean dialysis age=30.1+/-10.0 months), in which cellulosic (CLS) and vitamin E-modified dialyzers (CLE) were compared. At inclusion all the patients were treated with CLS. Then, the study group was shifted to CLE for 6 months. At baseline the patients showed normal levels of vitamin E and high levels of oxLDL-Ab, vWf and TM compared to healthy subjects. In the CLE group oxLDL-Ab and vWf, but not TM levels, decreased progressively (from 472+/-287 to 264+/-199 mU/mL, p<0.0001 and from 101.1+/-7.5% to 76.7+/-18.5%; p<0.001, respectively), and vitamin E increased from 4.40+/-0.81 to 7.81+/-1.16 microg/mg of cholesterol. At the end of the study, 8 of the patients treated with CLE were randomly selected and went back to the membrane without Vitamin E for six months. They showed an significant increase in OxLDL-Ab and vWf levels and a significant reduction in tocoferol levels. In conclusion, CLE compared to cellulosic dialyzers can lower some indices of damage to LDL and endothelial cells.
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PMID:Von Willebrand factor and autoantibodies against oxidized LDL in hemodialysis patients treated with vitamin E-modified dialyzers. 1511 87


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