Cross‐talk between Toll‐like receptors and renin angiotensin system in a cardiac hypertrophy model induced by renal ischemia/reperfusion (404.5)

Abstract

Objectives: The cardio‐renal syndrome comprises a set of pathophysiological kidney‐heart interactions. Renal inflammatory conditions are able to promote the release of inflammatory cytokines, which may act through cardiac TLR, promoting cardiovascular diseases such as cardiac hypertrophy (CH), as well as angiotensin II. This study aims to investigate a possible interaction between TLR and RAS in a model of CH induced by ischemic renal injury. Methods: C57BL/6 male mice (n=85) were subjected to surgical occlusion of left renal pedicle. Mice were treated with Los (10 mg/kg/day) or Ena (40 mg/kg/day) and kept under observation for 12, 15 or 20 days of reperfusion (REP). Kidney injury and CH were assessed by morphologic and molecular parameters. Cardiac and serum cytokines and protein and mRNA levels of cardiac RAS components and TLR2 and TLR4 were evaluated. Results: The succesfully‐performed ischemic protocol induced CH after 12d of REP, which was accompanied by enhanced IL‐6 levels in serum. CH were completely reversed by Los and Ena treatment. At the same time point, cardiac AT1, ACE2, TLR2 and TLR4 levels were increased (p<0.001). Treatment with RAS inhibitors abolished this increase to levels similar to control group. Conclusion: RAS may modulate CH through regulation of TLRs levels in the heart, suggesting the existence of a important cross‐talk between TLR and RAS in CH induced by renal ischemia/reperfusion.