Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion and transendothelial migration of leukocytes into the vascular wall is a crucial step in atherogenesis. Expression of cell adhesion molecules by endothelial cells plays a leading role in this process. We investigated the effect of simvastatin, an inhibitor of HMG-CoA reductase administered to reduce plasma levels of LDL-cholesterol, on the expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) by human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor alpha (TNFalpha). We found the expression to be significantly inhibited by the drug in a time and concentration-dependent manner and to a greater extent in the case of VCAM-1 as compared with ICAM-1. In TNFalpha-stimulated HUVEC, simvastatin decreased VCAM-1 and ICAM-1 mRNA levels, inhibited TNFalpha-induced activation of nuclear factor kappaB (NF-kappaB) and enhanced expression of peroxisome proliferator-activated receptor alpha (PPARalpha). These effects were associated with reduction of adherence of monocytes and lymphocytes to HUVEC. The present findings suggest that the benefits of statins in vascular disease may include the inhibition of expression of VCAM-1 and ICAM-1 through effects on NF-kappaB.
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PMID:Simvastatin modulates TNFalpha-induced adhesion molecules expression in human endothelial cells. 1523 87

Adhesion and migration of leukocytes into the surrounding tissue are crucial steps in inflammation, immunity and atherogenesis. Expression of cell adhesion molecules by endothelial cells plays a role in these processes. Propionate is a naturally occurring short chain fatty acid produced by bacterial fermentation of dietary fibre. High intake of dietary fibre has been associated with an improved bowel function and with a reduced risk of cardiovascular disease. However, the molecular mechanisms responsible for these effects remain unknown. In this study, the effects of propionate on the expression of endothelial leukocyte adhesion molecules by cytokine-stimulated human umbilical vein endothelial cells (HUVEC) were investigated. Pretreatment of HUVEC with propionate significantly inhibited the tumor necrosis factor alpha (TNF-alpha)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in a time- and dose-dependent manner. At 10 mM, propionate also inhibited the interleukin-1 (IL- 1)-mediated VCAM-1 and ICAM-1 expression, with the latter effect being more pronounced, as well as decreased the TNF-alpha-induced VCAM-1 and ICAM-1 mRNA expression in a similar manner. The decrease in VCAM-1 and ICAM-1 expression was associated with a reduction of adherence of monocytes and lymphocytes to the cytokine-stimulated HUVEC. In addition, propionate significantly inhibited the TNF-alpha-induced activation of nuclear factor-kappa B (NF-kappaB) and significantly increased the expression of peroxisome proliferator-activated receptor alpha (PPARalpha) in HUVEC. These results demonstrate that propionate may have antiinflammatory and possibly antiatherogenic properties. Our findings warrant further investigation into the therapeutic effects of propionate on a number of pathological events nvolving leukocyte recruitment.
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PMID:Propionate reduces the cytokine-induced VCAM-1 and ICAM-1 expression by inhibiting nuclear factor-kappa B (NF-kappaB) activation. 1961 55