CTRP1 prevents sepsis-induced cardiomyopathy via Sirt1-dependent pathways

Abstract

C1q/tumor necrosis factor-related protein 1 (CTRP1) has recently been identified as a key regulator of cardio-metabolic diseases. It has been reported that CTRP1 could inhibit the hypertrophic response in mice. However, the effect of CTRP1 on sepsis-induced cardiomyopathy remains completely unknown. Cardiomyocyte-specific CTRP1 overexpression was achieved using an adeno associated virus system in mice. CTRP1 deficiency mice were also subjected to lipopolysaccharide (LPS) injection. We found that CTRP1 overexpression improved survival rate and cardiac function, and suppressed myocardial inflammation, oxidative damage and apoptosis without affecting metabolic disturbance in LPS-treated mice. CTRP1 depletion further decreased survival rate and cardiac function, and promoting myocardial inflammation, oxidative damage and apoptosis in sepsis mice. In addition, we showed that CTRP1 provided protection against LPS-induced cell injury in vitro. CTRP1 activated sirtuin 1 (Sirt1) signaling pathway, and Sirt1 inhibition or deficiency blocked CTRP1-mediated cardioprotective effects in vivo and in vitro. More importantly, our study found that recombinant human globular domain of CTRP1 infusion was also capable of blocking sepsis-induced cardiomyopathy in mice. In conclusion, CTRP1 improved survival rate and attenuated LPS-induced cardiac injury via activating Sirt1 signaling pathway.