Preexisting heart failure with reduced ejection fraction attenuates renal fibrosis after ischemia reperfusion via sympathetic activation

Abstract

Abstract Although chronic heart failure is clinically associated with acute kidney injury (AKI), the precise mechanism that connects kidney and heart remains unknown. Here, we elucidate the effect of pre-existing heart failure with reduced ejection fraction (HFrEF) on kidney via sympathetic activity, using the combining models of transverse aortic constriction (TAC) and unilateral renal ischemia reperfusion (IR). The evaluation of acute (24 h) and chronic (2 weeks) phases of renal injury following IR 8 weeks after TAC in C57BL/6 mice revealed that the development of renal fibrosis in chronic phase was significantly attenuated in TAC mice, but not in non-TAC mice, whereas no impact of pre-existing heart failure was observed in acute phase of renal IR. Expression of transforming growth factor-β, monocyte chemoattractant protein-1, and macrophage infiltration were significantly reduced in TAC mice. Lastly, to investigate the effect of sympathetic nerve activity, we performed renal sympathetic denervation two days prior to renal IR, which abrogated attenuation of renal fibrosis in TAC mice. Collectively, we demonstrate the protective effect of pre-existing HFrEF on long-term renal ischemic injury. Renal sympathetic nerve may contribute to this protection; however, further studies are needed to fully clarify the comprehensive mechanisms associated with attenuated renal fibrosis and pre-existing HFrEF.