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)

The effects of dietary soy isoflavones (IF) and conjugated equine estrogens (CEE) on circulating inflammatory markers were determined at the end of a 3-yr study of ovariectomized monkeys consuming a moderately atherogenic diet. Treatments were: 1) control, receiving alcohol-extracted soy-protein-based diet with low IF content (comparable to approximately 5 mg/d); 2) CEE, added to the control diet at a dose comparable to 0.625 mg/d; and 3) IF, consumed as a part of unextracted soy protein isolate at a dose comparable to 129 mg/d. Serum soluble vascular cell adhesion molecule-1 (sVCAM-1) was reduced by both IF (P < 0.006) and CEE (P < 0.0001) relative to controls. Serum monocyte chemoattractant protein (MCP)-1 was reduced by CEE (P < 0.0001) but not by IF (P = 1.00). Treatments did not affect serum IL-6 (P = 0.40), soluble E-selectin (P = 0.17), or C-reactive protein (P = 0.15). Serum MCP-1 and, to a lesser extent, IL-6 significantly correlated with atherosclerosis (plaque area) in the iliac and carotid arteries (all P < 0.05). Serum MCP-1 was also strongly associated with coronary artery atherosclerosis and with indices of plaque inflammation and matrix remodeling (matrix metalloproteinase-9) in the coronary artery intima (all P < 0.01). We conclude that, in this well-established nonhuman primate model of atherosclerosis, this dose of soy IF provided an antiinflammatory effect specific for sVCAM-1, whereas the effects of CEE extended to both sVCAM-1 and MCP1. It is possible that the atheroprotective effects of IF and CEE are mediated, at least in part, by effects on VCAM-1. The sites of IF inhibitory effects on sVCAM-1 production are not known, but likely candidates include the liver and/or the cardiovascular system.
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PMID:Effects of soy isoflavones and conjugated equine estrogens on inflammatory markers in atherosclerotic, ovariectomized monkeys. 1558 61

A role for infection and inflammation in atherogenesis is widely accepted. Arterial endothelium has been shown to express heat shock protein 60 (HSP60) and, since human (hHSP60) and bacterial (GroEL) HSP60s are highly conserved, the immune response to bacteria may result in cross-reactivity, leading to endothelial damage and thus contribute to the pathogenesis of atherosclerosis. In this study, GroEL-specific T-cell lines from peripheral blood and GroEL-, hHSP60-, and Porphyromonas gingivalis-specific T-cell lines from atherosclerotic plaques were established and characterized in terms of their cross-reactive proliferative responses, cytokine and chemokine profiles, and T-cell receptor (TCR) Vbeta expression by flow cytometry. The cross-reactivity of several lines was demonstrated. The cytokine profiles of the artery T-cell lines specific for GroEL, hHSP60, and P. gingivalis demonstrated Th2 phenotype predominance in the CD4 subset and Tc0 phenotype predominance in the CD8 subset. A higher proportion of CD4 cells were positive for interferon-inducible protein 10 and RANTES, with low percentages of cells positive for monocyte chemoattractant protein 1 and macrophage inflammatory protein 1alpha, whereas a high percentage of CD8 cells expressed all four chemokines. Finally, there was overexpression of the TCR Vbeta5.2 family in all lines. These cytokine, chemokine, and Vbeta profiles are similar to those demonstrated previously for P. gingivalis-specific lines established from periodontal disease patients. These results support the hypothesis that in some patients cross-reactivity of the immune response to bacterial HSPs, including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may explain the apparent association between atherosclerosis and periodontal infection.
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PMID:Characterization of heat shock protein-specific T cells in atherosclerosis. 1569 20

TL1A (VEGI/TNFSF15) is the ligand for DR3 (TNFRSF12) and is a newly identified member of the tumor necrosis factor superfamily (TNFSF). Previously, DR3 has been shown to have a role in atherogenesis through stimulation of matrix degrading enzymes including matrix metalloproteinase (MMP)-9. Immunohistochemical staining of human carotid atherosclerotic plaques revealed a high-level expression of TL1A in regions rich in macrophage/foam cells. To investigate the role of TL1A and DR3 in the functioning of macrophage/foam cells in relation to atherogenesis, we have analyzed cellular events mediated by TL1A and DR3 in a human macrophage-like cell line, THP-1. Treatment of THP-1 cells with immobilized anti-DR3 monoclonal antibody in combination with IFN-gamma caused induction of pro-atherogenic cytokines/chemokines such as TNF-alpha, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8. Treatment of THP-1 cells with recombinant TL1A in combination with IFN-gamma also caused induction of MMP-9 and IL-8. Furthermore, the expression of DR3 in peripheral blood monocytes was induced after atherogenic stimulation. These data suggest that TL1A and DR3 is involved in atherosclerosis via the induction of pro-inflammatory cytokines/chemokines and decreasing plaque stability by inducing extracellular matrix degrading enzymes.
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PMID:Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis. 1576 Jun 79

Inflammation plays an important role in the initiation and progression of atherosclerosis and the development of atherosclerotic events. Understanding the molecular basis of inflammation has led to the identification of markers that may also serve as new targets of therapy in the management of atherothrombotic disease. Inflammatory markers, such as C-reactive protein (CRP), have been shown to predict future cardiovascular events in individuals with and without established cardiovascular disease (CVD). Statins substantially reduce cardiovascular morbidity and mortality, and recently their anti-inflammatory properties have been investigated. In this paper, we discuss biomarkers implicated in the inflammatory process leading to atherothrombosis, including CRP, adiponectin, monocyte chemoattractant protein 1 (MCP-1), CD40 ligand and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), and the effect of statins on these markers and their potential relationship to cardiovascular events.
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PMID:Markers of inflammation and their clinical significance. 1582 93

Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis, fibrosis and vascular occlusion after radiation therapy. Statins have been reported to improve endothelial function; however, this beneficial effect on endothelial cells has never been investigated after irradiation. Therefore, using human microvascular endothelial cells from lung that had been irradiated with 5 or 10 Gy, we assessed the effect of pravastatin on endothelial activation by ELISA, cell-ELISA and electrophoretic mobility shift assay and increased blood-endothelial cell interactions by a flow adhesion assay. Pravastatin inhibited the overproduction of monocyte chemoattractant protein 1, IL6 and IL8 and the enhanced expression of intercellular adhesion molecule 1 but had no effect on platelet-endothelial cell adhesion molecule 1 expression. Moreover, pravastatin down-regulated the radiation-induced activation of the transcription factor activator protein 1 but not of nuclear factor-kappaB. Finally, an inhibition by pravastatin of increased adhesion of leukocytes and platelets to irradiated endothelial cells was observed. The effect of pravastatin was maintained up to 14 days after irradiation and was reversed by mevalonate. Pravastatin exerts persistent anti-inflammatory and anti-thrombotic effects on irradiated endothelial cells. Statins may be considered in therapeutic strategies for the management of patients treated with radiation therapy.
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PMID:Pravastatin limits endothelial activation after irradiation and decreases the resulting inflammatory and thrombotic responses. 1585 Apr 8

Several lines of evidence suggest a biological role for peroxisome proliferator-activated receptor (PPARdelta) in the pathogenesis of atherosclerosis. Administration of synthetic PPARdelta agonists to obese rhesus monkeys elevates serum high-density lipoprotein (HDL) cholesterol as a result of increased reverse cholesterol transport whilst in vitro studies have suggested a role for PPARdelta in lipid uptake into macrophages. Recent studies have found that PPARdelta depletion from macrophages in LDL receptor (LDLR(-/-)) mice decreases lesion area via modulation of the inflammatory status of the macrophage, an effect also seen on pharmacological activation of PPARdelta in vitro. We demonstrate here that the PPARdelta agonist, GW0742X has potent anti-atherogenic activity in the LDLR(-/-) mouse, decreasing lesion area by up to 50%. Administration of GW0742X had no effect on total cholesterol, HDL or LDL cholesterol and modest effects on very low-density lipoprotein (VLDL). Treatment with GW0742X resulted in decreased expression of monocyte chemoattractant protein 1 (MCP-1) and intracellular adhesion moleculae 1 (ICAM-1) in the aortae of treated mice. In addition, GW0742X decreased tumour necrosis factor-alpha (TNFalpha) expression in peritoneal macrophages, aortae and adipose tissue in comparison with control animals. Changes in gene expression were reflected in decreased plasma levels of MCP-1. These observations support an atheroprotective effect of PPARdelta agonists in vivo.
Atherosclerosis 2005 Jul
PMID:The PPARdelta agonist GW0742X reduces atherosclerosis in LDLR(-/-) mice. 1593 51

Since atherosclerosis has been proven to be an inflammatory disease, it is obvious that the proper treatment for dyslipidemia should not only correct lipid parameters but also inhibit inflammation. Monocytes and monocyte-derived proinflammatory cytokines are widely known to be involved in the formation and rupture of the atherosclerotic plaque. The aim of our study was to assess the effect of fenofibrate, a commonly used hypolipidemic drug, on the release of interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) by monocytes from patients with combined hyperlipidemia. Fourteen patients with biochemically confirmed type IIb dyslipidemia who did not respond to a low-fat diet were treated with micronized fenofibrate for 1 month. The control group included 12 healthy, normolipidemic, age-matched subjects. To accurately evaluate the levels of the inflammatory cytokines, we excluded patients with any inflammatory disease. Monocytes were isolated from peripheral blood before and after the treatment. IL-1beta, IL-6 and MCP-1 release was measured by enzyme-linked immunosorbent assay (ELISA) after lipopolysaccharide stimulation. IL-1beta, IL-6 and MCP-1 levels were significantly higher in hyperlipidemic patients compared to the control (143.9 +/- 6.5 vs. 74.4 +/- 4.4 pg/ml; 8212 +/- 285 vs. 6110 +/- 170 pg/ml; 19.6 +/- 0.9 vs. 12.3 +/- 0.6 ng/ml, respectively). Thirty-day fenofibrate treatment decreased the release of IL-1beta by 43% (143.9 +/- 6.5 vs. 86.2 +/- 5.9 pg/ml), of IL-6 by 22% (8212 +/- 285 vs. 6330 +/- 234 pg/ml), and of MCP-1 by 29% (19.6 +/- 0.9 vs. 14.0 +/- 0.8 ng/ml). The evaluated cytokines were markedly elevated in patients with type IIb dyslipidemia. Effective fenofibrate therapy had a significant inhibitory effect on the release of monocyte-derived inflammatory cytokines.
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PMID:Monocyte suppressing action of fenofibrate. 1598 20

Chemokine-driven migration of inflammatory cells has been implicated in pathogenesis of atherosclerosis-associated conditions such as ischemic stroke and myocardial infarction. In this study, a candidate chemokine, monocyte chemoattractant protein (MCP)-1, was investigated in patients with both aforementioned manifestations of atheroslerotic inflammation. MCP-1 levels in serum were determined by ELISA in 40 healthy, control subjects (C), 40 patients with ischemic stroke (IS), and in 64 patients with myocardial infarction (MI). Statistical analysis utilised Mann-Whitney test, Fisher's exact test, and Spearman's rank correlation (P < .05). In comparison to control subjects (C; median/interquartile range: 239/126 pg/mL), MCP-1 serum levels were increased in both investigated patient cohorts (IS: 384/370, P < .001; MI: 360/200, P < .002). There was a substantial variability of MCP-1 serum levels, especially in the IS group. No relationship was observed between chemokine levels and atherosclerosis risk factors (hypertension, diabetes, smoking, and alcohol consumption), and MCP-1 was also not related to age or gender. Elevation of MCP-1 in circulation of patients with atherosclerosis-associated complications implicates this CC chemokine ligand (CCL)2 in inflammatory processes, which contribute to pathogenesis of myocardial infarction and ischemic stroke. Further investigations, including patient stratification, are however necessary to evaluate if MCP-1 can be utilised for clinical management of patients with these diseases.
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PMID:Serum levels of the MCP-1 chemokine in patients with ischemic stroke and myocardial infarction. 1610 5

Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE-/- mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE-/- mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.
Atherosclerosis 2005 Oct
PMID:The potential role of resistin in atherogenesis. 1615 96

Leukocyte recruitment and adhesion to the endothelium are critical steps in the early phase of atherosclerosis. Synthetic ligands of peroxisome proliferator-activated receptors (PPARs) were shown to reduce cytokine-stimulated leukocyte-endothelial cell interactions by inhibiting the NF-kappaB mediated inflammatory response. Conjugated linoleic acids (CLA), which are natural ligands of PPARs, were demonstrated to have anti-inflammatory and anti-atherogenic properties in vivo. With a view to elucidating the anti-atherogenic mechanisms of CLA, the present study aimed to explore the effects of cis-9, trans-11 CLA and trans-10, cis-12 CLA on cytokine-induced chemokine release, surface expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and U937 monocyte adhesion in human aortic endothelial cells (HAEC). Treatment of HAECs with 2 ng/mL of TNFalpha markedly increased expression of adhesion molecules, U937 monocyte adhesion, and release of the monocyte chemoattractant protein (MCP)-1. However, treatment of HAECs with either CLA isomer or linoleic acid did not modulate the cytokine-induced expression of ICAM-1, VCAM-1, and E-selectin, U937 cell adhesion and MCP-1 release. In addition, both CLA isomers and linoleic acid slightly increased PPARgamma DNA-binding activity, but did not alter DNA-binding activity of NF-kappaB. In conclusion, CLA isomers showed no effect on cytokine-induced monocyte-endothelial cell interactions and on the molecular mechanisms regulating these processes in HAEC. This study suggests that anti-atherogenic effects of CLA observed in vivo are probably not mediated by reduced monocyte-endothelial cell interactions.
Atherosclerosis 2006 Jun
PMID:Conjugated linoleic acids have no effect on TNF alpha-induced adhesion molecule expression, U937 monocyte adhesion, and chemokine release in human aortic endothelial cells. 1621 13


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