Background Resistin is an adipocyte secreted molecule induced during adipocyte differentiation. Recombinant resistin up regu lates cytokines and adhesion molecule expression on human endothelial cells, suggesting a potential role in atherosclerosis. Resistin has been shown to have potent proinflammatory properties.Resistin promotes endothelial cell activation and Tenatoprazole? causes endothelial selleckchem Pacritinib dys function of porcine coronary arteries. Recently, resistin was found to have a potential role in atherosclerosis because resistin increases MCP 1 and sVCAM 1 expres sion in vascular endothelial cells and resistin promotes vascular smooth muscle cell proliferation. More recently, resistin was found to be secreted from macro phages in atheromas and promotes atherosclerosis.
Plasma resistin levels are correlated with markers of inflammation and are predictive of coronary atherosclero sis in humans, independent of plasma C reactive pro tein. Resistin may represent a novel link between metabolic signals, inflammation, and atherosclerosis. The 3 hydroxy 3 methyl glutaryl CoA reductase inhibitors or statins have been proved to reduce inflammation and exert beneficial effects in the prevention of atherosclerosis progression. The pleio tropic effect of statins, independent of their lipid lowering effects have been described to improve endothelial func tion, stabilize atheroslerotic plaque, inhibit vascular smooth muscle cell proliferation as well as platelet aggre gation, and reduce vascular inflammation.
Ichida et al reported that atorvastatin decreases resistin expression in adipocytes and monocytes macrophages.
Atorvasta tin decreased resistin mRNA expression in a dose and time dependent manner. However, the mechanism of reducing resistin expression by atorvastatin is not known. Therefore, we sought to investigate the molecular mecha nisms of atorvastatin Batimastat for reducing resistin expression after proinflammatory GSK-3 cytokine, TNF stimulation in macro phages. Materials and methods Drugs Atorvastatin, a calcium salt of a pentasubstituted pryole, was supplied by Pfizer. A 10 mmole l stock solution was made in inhibitor licensed 100% DMSO. Recombinant TNF protein and mevalonate were purchased from Sigma. Polyclonal Rac, and polyclonal phospho Rac1 antibodies from Cell Signaling. Resistin antibody from R D Systems. Rac 1 inhibitor, PD 98059, SB 203580, and anisomycin from quality control CALBIOCHEM. Resistin siRNA from Invitrogen. Cell culture Human peripheral mononuclear cells were iso lated from heparinized whole blood obtained from nor mal healthy volunteers by Ficoll Hypaque gradient centrifugation.