Abrogation of lectin-like oxidized LDL receptor-1 attenuates acute myocardial ischemia-induced renal dysfunction by modulating systemic and local inflammation
Objective To It is assumed, but never proven, that acute myocardial infarction affectsrenal function. We tested this phenomenon in mice subjected to left coronary artery ( LCA) ligation.Further, we tested the hypothesis that LOX-1 abrogation may inhibit systemic inflammation, collagenaccumulation and attenuate renal dysfunction following LCA occlusion. Methods Wild-type (WT) andLOX-1 KO mice were subjected to permanent LCA ligation resulting in extensive myocardial infarction.Cardiac function was analyzed by echocardiography on Day 3 and on Day 21 post-surgery. Renal function andmorphology were assessed at the same time points. The pro-inflammatory signals and markers of fibrosis weremeasured in the serum and kidney. Results Soon after LCA ligation, there was a marked in rise in pro-inflammatory cytokines and MDA levels in circulation in the WT mice. On Day 3, renal function assessmentshowed a marked decline in association with swelling of gomeruli and tubules and mild fibrosis ( P < 0. 05 vs.Sham LCA ligation). There was a significant increase in the expression LOX-1, IL-1 (5 and VCAM-1,TBARS levels, and markers of fibrosis (collagen IV and procollagen-I) in the kidney. On Day 21, renalfunction showed some recovery, but there was extensive fibrosis in the kidneys accompanied with worse LVfunction. LOX-1 KO mice subjected to total LCA ligation showed much less increase in systemic and renalpro-inflammatory cytokines and MDA levels, and much less structural alterations and functional decline thanthe WT mice (all P <0. 05). Cardiac function and survival rate were better in the LOX-1 KO mice than inthe WT mice ( P < 0. 05). Conclusions We demonstrate for the first time that severe myocardial ischemiaresults in renal dysfunction and histologic abnormalities reminiscent of acute renal injury. LOX-1 deletion byreducing pro-inflammatory and pro-oxidant signals results in significantly less renal abnormality anddysfunction. This study suggests that LOX-1 is a key modulator among the multiple mechanisms underlyingcardio-renal syndrome.
LOX-1 inflammation myocardium infarction renal function
吕箐君 魏捷 Wang Xianwei Jawahar L．Mehta
武汉大学人民医院急诊室 Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, USA Depart
国内会议
西宁
英文
181-182
2012-08-01（万方平台首次上网日期，不代表论文的发表时间）