HMG CoA Reductase Inhibitors Reduce Plasminogen Activator Inhibitor-1 Expression by Human Vascular Smooth Muscle and Endothelial Cells

作者：ToddBourcier, PeterLibby · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2000 · 被引用次数：233 · 研究领域：Lipoproteins and Cardiovascular Health、Protease and Inhibitor Mechanisms、Cell Adhesion Molecules Research

Abstract—The clinical benefit of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may derive from a qualitative, functional change in atherosclerotic lesions in addition to their lipid-lowering properties. We examined whether statins altered expression of the major determinants of fibrinolytic balance, plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator (tPA) in human vascular smooth muscle (SMC) and endothelial (EC) cells. Simvastatin reduced levels of PAI-1 antigen released from SMCs and ECs stimulated with platelet-derived growth factor or transforming growth factor-β (IC50 ≈1 μmol/L). Levels of EC-derived tPA increased 2-fold over the same concentrations of simvastatin that inhibited release of PAI-1. Simvastatin’s inhibitory effect was mimicked by C3 exoenzyme and prevented by geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate, suggesting the involvement of geranylgeranyl-modified intermediates. Decreased PAI-1 antigen was correlated with ...