Advanced oxidation protein products accelerate atherosclerosis through promoting oxidative stress and inflammation.
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.


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)-alpha levels.


CONCLUSIONS
This study provides in vivo evidence for a causal relationship between chronic AOPPs accumulation and atherosclerosis.
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
Shang Xi
SX
Liu
Fan Fan
FF
Hou
Zhi Jian
ZJ
Guo
Ryoji
R
Nagai
Wei Ru
WR
Zhang
Zhi Qiang
ZQ
Liu
Zhan Mei
ZM
Zhou
Mei
M
Zhou
Di
D
Xie
Guo Bao
GB
Wang
Xun
X
Zhang
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D001798:Blood Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood; D007249:Inflammation / Q000150:complications*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001798:Blood Proteins; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein