Starvation Induces Diverse Autophagic Response in Cardiomyocytes and Noncardiomyocytes.

Abstract

Cardiac autophagy serves as a potential mechanism to be genetically, epigenetically and pharmaceutically manipulated to prevent or alleviate pathological conditions in heart diseases. One of the complexities of this manipulation comes from the cellular heterogeneity of the heart. In this study, we assessed the dynamics of nutrient deprivation-induced autophagy activation in four major cardiac cell types in vitro and in vivo and found a major difference between cardiomyocyte and other three types of noncardiomyocyte. In comparison to the constant increase and maintenance of autophagic activity in noncardiomyocytes, cardiomyocyte undergoes rapid gain and loss of autophagic activity. This difference contributes to at least two aspects of cardiomyocyte pathophysiology: high vulnerability to nutrient deprivation-induced cell death and unresponsiveness to pharmaceutical regulation of autophagy. Our present findings support a cell type-specific targeting of autophagy for therapeutic intervention of cardiac diseases.