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. Key Words: advanced oxidation protein products Ⅲ atherosclerosis Ⅲ hypercholesterolemia Ⅲ inflammation Ⅲ oxidative stress T he high prevalence of atherosclerotic lesions has been amply documented in patients with chronic renal failure (CRF). 1,2 However, the factors that may promote atherosclerosis in CRF patients remain to be determined. Of particular importance in this context may be the recent observation of 3 who found that advanced oxidation protein products (AOPPs) significantly increased in patients with CRF. Conclusions-ThisBiochemical characterization has revealed that AOPPs are carried by plasma proteins, especially albumin. 3 AOPPs can be formed in vitro by exposure of serum albumin to hypochlorous acid (HOCl). In vivo, plasma concentration of AOPPs closely correlated with levels of dityrosine, a hallmark of oxidized protein, and pentosidine, a marker of protein glycoxidation tightly related to oxidative stress. 4 Thus, AOPPs might be formed during oxidative stress by reaction of plasma proteins with chlorinated oxidants, and have been considered as novel markers of oxidant-mediated protein damage. 3 More interesting is the finding that AOPPs are highly correlated to carotid intima media thickness 5 and may even be related to atherosclerotic cardiovascular events. 6 More recently, increased levels of AOPPs were also found in diabetic 7,8 and nonuremic subjects with coronary artery disease, 9 suggesting that accumulation of AOPPs may be relevant in atherosclerosis and not uremia-specific. However, although the observational studies suggest a close relationship between AOPPs and atherosclerosis,...

Accumulation of plasma advanced oxidation protein products (AOPP) has been found in patients with chronic kidney disease. However, the biologic consequences of AOPP consumption on progression of renal disease still are unclear. For testing of the hypothesis that AOPP accelerate progression of chronic kidney disease, Sprague-Dawley rats were subjected to five-sixths nephrectomy (5/6 Nx) or to sham operation. Rats in each group were randomly assigned in three subgroups (n ‫؍‬ 30 in each group) and treated with repeated intravenous injections of AOPP-modified rat serum albumin (RSA), unmodified RSA, or vehicle for indicated period. Compared with RSA-or vehicle-treated 5/6 Nx rats, AOPP RSA-treated 5/6 Nx rats displayed greater proteinuria, higher serum creatinine, and lower creatinine clearance. AOPP challenge resulted in more renal hypertrophy, higher macrophage influx, and greater renal fibrosis in the remnant kidney. Chronic administration of AOPP in sham-operated rats increased urinary protein excretion and renal macrophage infiltration, but histologic renal fibrosis was not observed during the study period. AOPP treatment enhanced AOPP level in renal tissue. This was associated with marked increase of thiobarbituric acid reactive substances, decrease of glutathione peroxidase activity, and upregulated expression of monocyte chemoattractant protein-1 and TGF-␤1 in renal cortex. These data indicate that AOPP might be a new and potentially important mediator of renal fibrosis in the remnant kidney. Chronic accumulation of AOPP promotes renal fibrosis probably via a redox-sensitive inflammatory pathway.

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