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.
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.
Authors: Renata da Silva Pereira; Etiane Tatsch; Guilherme Vargas Bochi; Helena Kober; Thiago Duarte; Greice Franciele Feyh dos Santos Montagner; José Edson Paz da Silva; Marta Maria Medeiros Frescura Duarte; Ivana Beatrice Mânica da Cruz; Rafael Noal Moresco Journal: Inflammation Date: 2013-08 Impact factor: 4.092
Authors: Jun Wang; Min Liang; Jie Xu; Wei Cao; Guo B Wang; Zhan M Zhou; Jian W Tian; Nan Jia; Zhenhai Zhang; Jing Nie; Youhua Liu; Fan F Hou Journal: Lab Invest Date: 2014-07-28 Impact factor: 5.662
Authors: Gunther Marsche; Sasa Frank; Andelko Hrzenjak; Michael Holzer; Sabine Dirnberger; Christian Wadsack; Hubert Scharnagl; Tatjana Stojakovic; Akos Heinemann; Karl Oettl Journal: Circ Res Date: 2009-01-29 Impact factor: 17.367