Caveolin-1-Autophagy Pathway Mediated Cardiomyocyte Hypertrophy Induced by Apelin-13.

Abstract

Apelin, an endogenous ligand for apelin receptor (APJ), is reported to be involved in cardiomyocyte hypertrophy. In this study, we explored the mechanism of cardiomyocyte hypertrophy induced by apelin-13/APJ system. Left ventricular hypertrophy (LVH) rat model was established by constricting the abdominal aorta. Western blots were used for protein expression in LVH rats and cultured H9c2 cardiomyocytes. Transmission electron microscopy (TEM) was used to monitor morphological features of cells. In addition, the diameter and volume of H9c2 cells were detected by Scepter™ Handheld Automated Cell Counter. We found that the APJ was increased, but caveolin-1 was decreased in heart of LVH rats. In addition, caveolin-1 was suppressed by apelin-13, and this effect was reversed by APJ antagonist F13A in cultured H9c2 cardiomyocytes. Apelin-13 not only stimulated the formation of autophagolysosomes, autophagosome, and lysosomes but also increased the expression of autophagic markers Beclin-1 and LC3II/I. Besides, the increase of Beclin-1 and LC3 II/I was reversed by F13A or caveolin-1 overexpression and further enhanced by caveolin inhibitor. Furthermore, the cardiomyocyte hypertrophy index brain natriuretic peptide (BNP) induced by apelin-13 was blunt by F13A or autophagy inhibitor 3-methyladenine and further promoted by caveolin inhibitor. And caveolin-1 overexpression reduced the diameter and volume of H9c2 cells induced by apelin-13. Our study indicates that caveolin-1-autophagy pathway mediated cardiomyocyte hypertrophy induced by apelin-13/APJ system, which might provide a novel therapeutic target for cardiac hypertrophy disease.