Golgi protein 73 promotes LPS-induced cardiac dysfunction via mediating myocardial apoptosis and autophagy

Abstract

Sepsis-induced cardiac dysfunction represents a major cause of high mortality in intensive care units with limited therapeutic options. Golgi protein 73 (GP73) has been implicated in various diseases. However, the role of GP73 in LPS-induced cardiac dysfunction is unclear. Here, we established sepsis-induced cardiac dysfunction model by LPS administration in wild type (WT) and GP73 knockout (GP73 -/- ) mice. We found GP73 was increased in LPS-treated mouse hearts and LPS-cultured neonatal rat cardiomyocytes (NRCMs). Knockout of GP73 alleviated myocardial injury and improved cardiac dysfunction. Moreover, depletion of GP73 in NRCMs relieved LPS-induced cardiomyocyte apoptosis and activated myocardial autophagy. Therefore, GP73 is a negative regulator in LPS-induced cardiac dysfunction by promoting cardiomyocyte apoptosis and inhibiting cardiomyocyte autophagy.