Advanced oxidation protein products accelerate atherosclerosis through promoting oxidative stress and inflammation
Advanced oxidation protein products accelerate atherosclerosis through promoting oxidative stress and inflammation
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DOI：
10.1161/01.atv.0000214960.85469.68
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发表时间：
2006-05-01
影响因子：
8.7
通讯作者：
Zhang, X
中科院分区：
文献类型：
--
作者：
Liu, SX;Hou, FF;Zhang, X
目的：尿毒症和非尿毒症冠心病患者血浆晚期氧化蛋白产物（AOPP）水平升高。本研究进行测试的假设，AOPPs发挥因果关系的作用，在atherosclerosis.Methods和Results -高胆固醇血症（0.5%wt/wt饮食）或正常的兔子接受重复静脉注射AOPPs修改的兔血清白蛋白（AOPPs-RSA）或未修改的RSA 8周。与RSA或溶剂处理的高胆固醇血症兔相比，AOPPs-RSA处理的动物显示动脉粥样硬化斑块面积增加，氧化低密度脂蛋白（oxLDL）沉积，巨噬细胞浸润和平滑肌细胞增殖。AOPPs-RSA处理的正常家兔的主动脉切片显示受影响区域的显著局灶性内膜增殖和轻度油红O染色脂质沉积，在RSA或溶剂处理的对照中未观察到这种现象。AOPPs处理组血浆AOPPs水平在高胆固醇血症和正常家兔中均显著高于相应对照组。血浆AOPPs水平与氧化应激参数（如oxLDL和硫代巴比妥酸反应物质水平或谷胱甘肽过氧化物酶活性）密切相关。血浆AOPPs和肿瘤坏死因子（TNF）-α levels.Conclusions之间也观察到一个高度显着的相关性-这项研究提供了在体内的证据慢性AOPPs积累和动脉粥样硬化之间的因果关系。
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)-alpha levels.Conclusions - This study provides in vivo evidence for a causal relationship between chronic AOPPs accumulation and atherosclerosis.