on February 23, 2006
Published online before print February 23, 2006, doi: 10.1161/01.ATV.0000214960.85469.68
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Submitted on September 13, 2005
Accepted on February 5, 2006
Advanced Oxidation Protein Products Accelerate Atherosclerosis Through Promoting Oxidative Stress and Inflammation
Shang Xi Liu ;
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, Nanfang Medical University, Guangzhou, PR China; and the Department of Medical Biochemistry (R.N.), Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University.
* To whom correspondence should be addressed. 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.
Key words: advanced oxidation protein products • atherosclerosis • hypercholesterolemia • inflammation • oxidative stress
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