Lipid-lowering Drugs Inhibit The Molecular Pathology Of Arterial Intimal Hyperplasia After Intimal Injury

The relation between total cholesterol and LDL cholesterol levels and the incidence of CAD is well established. oxLDL is believed to play a key role as a triggering molecule in the earliest phase of atherosclerosis. HDL and apoAl act at the cellular level by increasing the resistance of endothelial cells against the cytotoxicity of oxidized LDL. It is noticed that although the success rate is high and up to 95%, 30-50% patients develop restenosis within 3-6 months right after percutanieous transluminal coronary angioplasty(PTCA), and endothelial injury or dysfunction occurs after PTCA, to promote the migration of smooth muscle cells from the media to intima, where SMC become further proliferated under the influence of platelet-derived growth factor(PDGF), basic fibroblast growth factor(bFGF), tissue growth factor(TGF), and LDL. The process of restenosis includes: l)thrombosis formation; 2)inflamatory processes; 3)proliferation of VSMC; 4)formation and disposition of extracellular matrix; 5)vessel remodeling. The proliferated smooth muscle cells, together with macrophages, fibrous tissue, and lipid, form the atherosclerotic plaque. Growth factors, such as PDGF, not only promotes cell proliferation or growth, but also protects cells from dying by suppressing apoptosis; TGF— β 1 stimulates the formation and deposition of extracellular matrx, suppresses inflammatory processes, and suppresses the proliferation of SMC; bFGF was found to stimulate neointima formation and to prevent apoptosis in VSMC.Until recently, remarkable lipid lowering in patients with CAD using HMG-CoA reductase inhibitors (statins family) has been learned to be the most effective means in terms of slowing or arrest of progression of coronary atherosclerosis. However, it is still unknown whether statins have any protective effect against intima proliferation promoted by growth factors.In our study, first, experimental hyperlipidemia models were established by cholesterol feeding in NZW rabbits. Serum TC were assayed, slot blot were used to analyze the expression of apoAl mRNA in liver and intestine. Then, the model of rabbit artery restenosis was set up after balloon catheter-induced de-endothelialization and high dosage of cholesterol intake. simvastatin and gemfibrozil were used to prevent intima proliferation. Serum cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and activity of lecithin-...