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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1156.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Advanced Oxidation Protein Products Accelerate Atherosclerosis Through Promoting Oxidative Stress and Inflammation

Shang Xi Liu; Fan Fan Hou; Zhi Jian Guo; Ryoji Nagai; Wei Ru Zhang; Zhi Qiang Liu; Zhan Mei Zhou; Mei Zhou; Di Xie; Guo Bao Wang; Xun Zhang

From the Division of Nephrology (S.X.L., F.F.H., Z.J.G., W.R.Z., Z.Q.L., Z.M.Z., M.Z., D.X., G.B.W., X.Z.), Nanfang Hospital, Southern Medical University, Guangzhou, PR China; and the Department of Medical Biochemistry (R.N.), Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University.

Correspondence to Dr Fan-Fan Hou, Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, PR China. E-mail ffhou{at}public.guangzhou.gd.cn

Objective— Increased level of plasma advanced oxidation protein products (AOPPs) has been found in patients with uremia and nonuremic subjects with coronary artery disease. This study was conducted to test the hypothesis that AOPPs play a causal role in atherosclerosis.

Methods and Results— Hypercholesterolemic (0.5% wt/wt diet) or normal rabbits received either repeated intravenous injections of AOPPs modified rabbit serum albumin (AOPPs-RSA) or unmodified RSA for 8 weeks. Compared with RSA- or vehicle-treated hypercholesterolemic rabbits, AOPPs-RSA–treated animals displayed increased atherosclerotic plaque area oxidized low-density lipoprotein (oxLDL) deposition, macrophage infiltration, and smooth muscle cell proliferation. Aortic sections from AOPPs-RSA–treated normal rabbits showed significant focal intima proliferation and mild Oil-Red-O staining lipid deposition in the affected areas, a phenomenon not observed in the RSA- or vehicle-treated controls. Plasma AOPPs levels in AOPPs-treated groups significantly increased in both hypercholesterolemic and normal rabbits compared with their relevant controls. Close correlations were found between plasma levels of AOPPs and the parameters of oxidative stress, eg, oxLDL and thiobarbituric acid reactive substances levels, or glutathione peroxidase activity. A highly significant correlation was also observed between plasma AOPPs and tumor necrosis factor (TNF)- levels.

Conclusions— This study provides in vivo evidence for a causal relationship between chronic AOPPs accumulation and atherosclerosis.

Increased levels of plasma advanced oxidation protein products (AOPPs) have been found in patients with uremia and in subjects with coronary artery disease. This study investigated the role of AOPPs in the development of atherosclerosis. The results demonstrated that AOPPs accelerate atherosclerosis via enhancing oxidative stress and inflammation.

Key Words: advanced oxidation protein products • atherosclerosis • hypercholesterolemia • inflammation • oxidative stress

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