Abstract 9519: Acute Myocardial Ischemia Results in Renal Dysfunction via Systemic and Local Inflammation and Oxidant Stress, and LOX-1 Abrogation Attenuates This Phenomenon
Aims It is assumed that acute myocardial infarction (MI) affects renal function.We tested this assumption in mice subjected to left coronary artery (LCA) occlusion. We also tested the hypothesis that LOX-1 deletion may inhibit systemic inflammation and oxidant stress and reduce renal dysfunction following MI.
Methods Wild-type (WT) and LOX-1 KO mice were subjected to total and permanent LCA occlusion resulting in acute and extensive MI.Cardiac function (LVEF) was analyzed by echocardiography at days 3 and 21 post-MI.Renal function (serum BUN and creatinine) and morphology (H&E and trichrome staining) were assessed at same time points.The pro-inflammatory signals and markers of fibrosis were measured by Western blotting in the renal tissues.
Results On day 3 after LCA ligation, there was a marked rise in pro-inflammatory cytokines in circulation (Multiplex system®). Importantly, there was a decline in renal function in association with >2-fold increase in renal mass,swelling of renal gomeruli and tubules and mild fibrosis in the renal medulla. There was a significant increase in the expression IL- 1β and VCAM-1, LOX-1, NADPH oxidase, and markers of fibrosis (collagen IV, procollagen-I and fibronectin) in renal tissues. On day 21, renal size was smaller, renal function and morphology were improved except for more fibrosis, and signals of inflammation and oxidant stress were less marked (P<0.05 vs. day 3). Deletion of LOX-1 resulted in a marked decline in systemic and renal pro-inflammatory and oxidant stress markers(all P<0.05 vs. wild-type mice) and better renal function. Cardiac function as well as survival were better in LOX-1 KO mice than in the wild-type mice (P<0.01) - all subjected to total LCA occlusion.
Conclusion We demonstrate that acute MI results in renal dysfunction and histologic abnormalities reminiscent of acute injury to the kidneys. LOX-1 deletion by reducing pro-inflammatory and pro-oxidant signals results in significantly less renal dysfunction.
- © 2011 by American Heart Association, Inc.