Targeting of cold-inducible RNA-binding protein alleviates sepsis via alleviating inflammation, apoptosis and oxidative stress in heart.

Abstract

A systemic inflammatory response is observed in patients undergoing shock and sepsis. This study aimed to explore the effects of cold-inducible RNA-binding protein (CIRP) on sepsis-associated cardiac dysfunction and the underlying mechanism. In vivo and in vitro lipopolysaccharide (LPS)-induced sepsis models were established in mice and neonatal rat cardiomyocytes (NRCMs), respectively. CRIP expressions were increased in the mouse heart and NRCMs treated with LPS. CIRP knockdown alleviated LPS-induced decreases of left ventricular ejection fraction and fractional shortening. CIRP downregulation attenuated the increases of inflammatory factors in the LPS-induced septic mouse heart, and NRCMs. The enhanced oxidative stress in the LPS-induced septic mouse heart and NRCMs was suppressed after CIRP knockdown. By contrast, CIRP overexpression yielded the opposite results. Our current study indicates that the knockdown of CIRP protects against sepsis-induced cardiac dysfunction through alleviating inflammation, apoptosis and oxidative stress of cardiomyocytes.