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)

This study investigated the expression of CD40, CD40 ligand (CD40L) and matrix metalloproteinases (MMPs) in dietary-induced atherosclerosis in rats. Wister rats were fed with high cholesterol diet (As group, n = 6) or with normal diet (N group, n = 6). Blood cells that express CD40 and CD40L were sorted by flow cytometry, the MMP-2 and MMP-9 were measured by zymography method. The morphological locations of MMP-2 and MMP-9 in the aorta were studied with immunohistochemistry and by microscopy. The results showed that the expression of CD40, CD40L and matrix metalloproteinase were higher in As group than those in control group. The MMP-2 and MMP-9 were positive in As group but negative in control group by immunohistochemistry study. Our results suggest that the expression of CD40 and CD40L in the blood cells and the activities of MMP-2 and MMP-9 in plasma were higher in As group than those in Normal group, indicating that they may contribute to the formation of atherosclerosis.
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PMID:The expression of CD40-CD40L and activities of matrix metalloproteinases in atherosclerotic rats. 1631 21

Incidence of atherosclerosis and atherosclerosis-related complications will increase significantly in the coming decennia. Research identified many serum and plasma markers that are associated with cardiovascular disease. However, little is known about the prognostic value of these markers to identify patients at risk for future cardiovascular events. Therefore, we aimed to investigate the prognostic value of three of these markers (soluble CD40 ligand (sCD40L), interleukin-6 (IL-6) and oxidized low-density lipoprotein (oxLDL)) with respect to coronary vascular disease and stroke. For this reason the Medline database was searched for the period January 1999-January 2005. To be selected in our study, concentration of the marker had to be determined at baseline, follow-up period had to be longer than 3 months and an estimate of relative risk had to be available. Based on these criteria, 4 studies for sCD40L, 10 for IL-6 and 2 for oxLDL were selected. Relative risk estimates adjusted for potential confounders varied between 1.9 and 2.8 for sCD40L, between 1.1 and 3.1 for IL-6 and between 1.9 and 3.2 for oxLDL. In conclusion, this systematic review shows that sCD40L, IL-6 and oxLDL are associated with an increased relative risk of developing cardiovascular disease.
Atherosclerosis 2006 Jul
PMID:Is there more than C-reactive protein and fibrinogen? The prognostic value of soluble CD40 ligand, interleukin-6 and oxidized low-density lipoprotein with respect to coronary and cerebral vascular disease. 1636 Jan 59

Individuals with chronically elevated glucose and/or insulin levels, i.e., most patients with type 2 diabetes, have accelerated atherosclerosis and are prone to acute vascular events. We have tested the hypothesis that hyperglycemia and/or hyperinsulinemia singly or combined may increase tissue factor, the primary initiator of blood coagulation. We have determined changes in circulating tissue factor procoagulant activity (PCA) and other procoagulation proteins in healthy volunteers exposed to 24 h of selective hyperinsulinemia, selective hyperglycemia, or combined hyperinsulinemia and hyperglycemia. Combined elevations of plasma insulin and glucose levels for 24 h produced a ninefold increase in tissue factor PCA, which was associated with an increase in monocyte tissue factor protein (flow cytometry) and mRNA (RT-PCR), increases in plasma thrombin-antithrombin complexes, prothrombin fragment 1.2, factor VIII coagulant activity, and platelet CD40 ligand as well as decreases in factor VIIa, factor VII coagulant activities, and factor VII antigen. Effects of selective hyperinsulinemia and selective hyperglycemia were less striking but appeared to be additive. We conclude that hyperinsulinemia and hyperglycemia but particularly the combination of both create a prothrombotic state and in addition may be proinflammatory and proatherogenic because of the proinflammatory actions of CD40 ligand and tissue factor.
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PMID:Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. 1638 Apr 94

Abdominal aortic aneurysms (AAA) are associated with atherosclerosis, transmural degenerative processes, neovascularization, decrease in content of vascular smooth muscle cells, and a chronic infiltration, mainly located in the outer aortic wall. The chronic infiltration consists mainly of macrophages, lymphocytes, and plasma cells. The dominant cells are Th2 restricted CD3+ lymphocytes expressing interleukine 4, 5, 8, and 10, and tumor necrosis factor-alpha for regulation of the local immune response. They also produce interferon-gamma and CD40 ligand to stimulate surrounding cells to produce matrix metalloproteases and cysteine proteases for aortic matrix remodeling. The lymphocyte activation may be mediated by microorganisms as well as autoantigens generated from vascular structural proteins, perhaps through molecular mimicry. As in autoimmune diseases, the risk of AAA is increased by certain genotypes concerning human leucocyte antigen class II. These types are also associated with increased aneurysmal inflammation indicating a genetic susceptibility to aortic inflammation. Chlamydia pneumoniae is often detected in AAA but the validity of the methods can be questioned, and two small antibiotic trials have been disappointing. However, serum antibodies against C. pneumoniae have been associated with AAA growth and cross-react with AAA wall proteins. Thus, immune responses mediated by microorganisms and autoantigens may play a pivotal role in AAA pathogenesis.
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PMID:Chronic inflammation, immune response, and infection in abdominal aortic aneurysms. 1641 93

Advanced glycation end products (AGEs), the senescent macroprotein derivatives that form in increased amounts in diabetes, have been implicated in the pathogenesis of accelerated atherosclerosis. There is a growing body of evidence that CD40-CD40 ligand (CD40L) interaction also plays an important role in atherogenesis. However, the effects of AGEs on CD40-CD40L signaling in endothelial cells (ECs) remain to be elucidated. In this study, we investigated (i) whether injection of AGE-proteins to normal rats stimulates CD40L expression on circulating platelets and (ii) whether AGEs up-regulate CD40 mRNA levels in cultured ECs. We further examined the effects of nifedipine, one of the most popular dihydropyridine-based calcium antagonists, on CD40 gene expression in AGE-exposed ECs. Platelet surface CD40L expression was increased in AGE-bovine serum albumin (AGE-BSA)-injected rats, compared with nonglycated BSA administration. AGEs were found to induce up-regulation of CD40 mRNA levels in ECs, which were significantly blocked by nifedipine. These results suggest that AGEs could enhance CD40-CD40L interaction, thereby promoting atherosclerosis in diabetes. Blockade of CD40-CD40L signaling in ECs may be a molecular target for the vasculoprotective property of nifedipine.
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PMID:Blockade by nifedipine of advanced glycation end product-induced CD40-CD40 ligand interaction in endothelial cells. 1642 79

Mounting evidence from a growing body of epidemiologic studies demonstrates that patients with systemic lupus erythematosus (SLE) are at increased risk for the development of premature cardiovascular disease (CVD). However, awareness of accelerated atherosclerosis in young SLE patients, albeit growing, is still limited, as documented by the brief case presented. Inflammation is thought to play an important role in both the pathogenesis of SLE, as well as atherosclerotic vascular disease. Inflammatory processes that are shared by SLE and atherosclerotic disease include immune complex deposition and fixation, autoantibody binding, complement activation and CD40-CD40 ligand interaction. By examining the inflammatory mechanisms in common between SLE and atherosclerotic disease, we can come to a better understanding of the pathophysiology of the accelerated atherosclerotic process seen in patients with SLE and can gain insights into developing and instituting preventative and treatment strategies. In this article, we present a case of a young woman with SLE who presents with chest pain, followed by a review of inflammation-based pathogenic mechanisms that are shared by SLE and atherosclerotic cardiovascular disease.
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PMID:Premature atherosclerotic disease in systemic lupus erythematosus--role of inflammatory mechanisms. 1643 36

CD40-CD40 ligand interaction is involved in the inflammatory pathogenesis of atherosclerosis but clinical data about its role in stent restenosis are still limited. We investigated the effect of preprocedural CD40 ligand (sCD40L) on stent restenosis. We enrolled 36 patients (mean age 61.4 +/- 8.5 years) with stable angina who underwent successful stent implantation. Control angiograms were performed in all patients after 6 months. Plasma sCD40L and high-sensitive C-reactive protein levels were measured before stent implantation and at 1 and 6 months after the procedure. Angiographically proven restenosis rate was 27.8%. Plasma sCD40L levels were significantly higher (preprocedural 0.74 +/- 0.79) and more prolonged in patients with stent restenosis compared with patients without stent restenosis (0.02 +/- 0.22 ng/ml, p < 0.001). According to receiver-operator characteristic analysis, sCD40L > 0.41 ng/ml was the best distinguished parameter between patients with and without restenosis. At the multivariate logistic regression analysis, preprocedural sCD40L was an independent predictor (RR 39.4, 95% confidence interval 4.05 to 383.8, p = 0.002) of stent restenosis after adjusting for confounding variables, including diabetes, reference vessel diameter, lesion length, stent diameter, stent length, and baseline high-sensitive C-reactive protein. Sensitivity, specificity, and positive and negative predictive values and likelihood ratio of preprocedural sCD40L levels in stent restenosis were 78%, 92%, 78%, 92%, and 9.37%, respectively. In conclusion, enhanced inflammation of plaque (increased sCD40L) before percutaneous coronary intervention may increase the rate of stent restenosis. Increased preprocedural sCD40L level is an independent predictor of stent restenosis. We can use this marker for the assessment of risk stratification before planning stent implantation.
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PMID:Usefulness of preprocedural soluble CD40 ligand for predicting restenosis after percutaneous coronary intervention in patients with stable coronary artery disease. 1644 63

Atherosclerosis (AT) is a chronic autoimmune inflammatory disease, characterized by lipoproteins metabolism alteration leading to formation of pro-inflammatory and pro-oxidative lipids and immune response. Identification of macrophages, T cells, pro-inflammatory cytokines, adhesion cell molecules in atherosclerotic lesions support the hypothesis that innate and adaptive immune response participate in the atherogenesis mechanism. Multiple factors such as inflammatory, infectious and immune system, among others participate in this process. The principal antigens identified in atherogenesis are: oxidized LDL (oxLDL), HSPs and beta2GPI. During LDL oxidation, multiple neoantigens are formed (anti-EO). These antibodies seem to be protective. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) have accelerated AT. The association of both diseases with AT suggests a common pathogenic mechanism. SLE and atherosclerosis are immune-complex mediated diseases. Participation of complement activation, and CD40, CD40 ligand interactions have been demonstrated in AT and SLE. AT may be the initial presentation or the consequence of primary antiphospholipid syndrome. The similarities between AT, SLE, and APS and the identification of protective antibodies offer opportunities for new immunomodulation treatment strategies.
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PMID:Accelerated atherosclerosis, immune response and autoimmune rheumatic diseases. 1648 19

The high incidence of cardiovascular complications in patients with chronic renal failure (CRF) is partly explained by more aggressive atherosclerosis, i.e. increased incidence and severity of lesions with higher tendency to calcification. The pathogenesis of this accelerated atherosclerosis, however, is not completely understood. Among other risk factors, chronic micro-inflammation may be involved. Activation of cells and adhesion molecules in atherosclerosis is governed by CD40-CD154 (CD40 ligand) interaction. Therefore, we investigated the expression and distribution of CD40-CD154 in different coronary atherosclerotic lesions of CRF patients and non-renal control patients. Coronary plaques of 57 patients with and without CRF were categorized according to the Stary classification and analysed for in situ protein expression of CD40, CD154 and CRP using immunohistochemistry and a semiquantitative scoring system. The nature, number and distribution of infiltrating cells was analysed and correlated to the types of coronary lesions and in particular to the presence of calcification. CD40 was over expressed in media myocytes of coronary plaques of both uremic and control patients. Inside the plaques, CD40 was expressed on endothelial cells, T lymphocytes, macrophages, fibroblasts, and smooth muscle cells. CD154 expression was seen on T cells in areas densely infiltrated by CD40 positive macrophages. In uremic and control patients higher in situ expression of CD40, CD154 and CRP was seen in calcified compared to non-calcified lesions. Inside the plaques, there were significant differences in the expression pattern of CD40 and CD154 between uremic and control patients. In addition, in uremic patients coronary plaques showed higher CRP protein expression compared to control patients. The data indicate a higher inflammatory status of coronary lesions as well as involvement of the CD40-CD154 signaling cascade in CRF patients, especially in cases of calcified atherosclerotic lesions.
Atherosclerosis 2007 Jan
PMID:CD40-CD154 expression in calcified and non-calcified coronary lesions of patients with chronic renal failure. 1649 85

The proinflammatory mediator CD40 ligand plays an important role in atherogenesis. Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared the effects of these therapies either alone or in combination on plasma soluble CD40 ligand (sCD40L). This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20mg and placebo, simvastatin 20mg and losartan 100mg, or losartan 100mg and placebo daily during each 2 month treatment period. Simvastatin alone did not significantly reduce sCD40L levels relative to baseline measurements when the entire cohort was analyzed. However, simvastatin significantly reduced sCD40L levels from 5.10+/-0.34 to 3.07+/-0.43ng/ml (P=0.002) in a subgroup of 18 patients with high baseline sCD40L levels >2.95ng/ml. Combined therapy or losartan alone significantly decreased plasma sCD40L levels relative to baseline measurements by 14+/-7% (P=0.001) and 13+/-10% (P=0.001), respectively. These decreases were significantly greater than those observed with simvastatin alone (P=0.023 by ANOVA). Significant inverse correlations between baseline sCD40L levels and percent changes in sCD40L levels were observed (r=-0.456, P=0.001 after simvastatin alone; r=-0.476, P<0.001 after combined therapy; r=-0.451, P=0.002 after losartan alone). Losartan alone or combined therapy significantly reduced plasma sCD40L levels more than simvastatin alone in our subjects. Simvastatin, losartan and combined therapy significantly reduced sCD40L to the greatest extent in patients with high baseline sCD40L levels.
Atherosclerosis 2007 Jan
PMID:The effects of simvastatin, losartan, and combined therapy on soluble CD40 ligand in hypercholesterolemic, hypertensive patients. 1650 Jun 62


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