Author:
Dominguez Jesus H.,Mehta Jawahar L.,Li Dayuan,Wu Pengfei,Kelly Katherine J.,Packer C. Subah,Temm Constance,Goss Erin,Cheng Liang,Zhang Shaobo,Patterson Carolyn E.,Hawes John W.,Peterson Richard
Abstract
LOX-1 is a multifunctional membrane receptor that binds and internalizes oxidized LDL (oxLDL). We tested the hypothesis that blockade of LOX-1 with an anti-LOX-1 antibody limits nephropathy in male rats with diabetes and dyslipidemia (ZS rats; F1hybrid product of Zucker fatty diabetic rats and spontaneous hypertensive heart failure rats). Lean ZS rats were controls, while untreated obese ZS (OM), ZS obese rats injected with nonspecific rabbit IgG (OM-IgG; 2 μg intravenous injection given weekly), and obese ZS rats given anti-LOX-1 rabbit antibody (OM-Ab; 2 μg intravenous injection given weekly) were the experimental groups. The rats were treated from 6 to 21 wk of age. All obese groups had severe dyslipidemia and hyperglycemia. Kidneys of obese rats expressed LOX-1 in capillaries and tubules, were larger, accumulated lipid, had intense oxidative stress, leukocyte infiltration, depressed mitochondrial enzyme level and function, and peritubular fibrosis (all P < 0.05 vs. lean ZS rats). Injections with LOX-1 antibody limited these abnormalities ( P < 0.01 vs. data in OM or OM-lgG rats). In vitro, renal epithelial LOX-1 expression was verified in a cultured proximal tubule cell line. Our study indicates that anti-LOX-1 (vascular and epithelial) therapy may effectively reverse critical pathogenic elements of nephropathy in diabetes and dyslipidemia.
Publisher
American Physiological Society
Cited by
42 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献