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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.