Adiponectin up‐regulates the decrease of myocardial autophagic flux induced by β₁‐adrenergic receptor autoantibody partly dependent on AMPK

Abstract

Abstract Cardiomyocytes autophagy is essential for maintaining cardiac function. Our previous studies have found that β 1 ‐adrenergic receptor autoantibody (β 1 ‐AA) induced the decreased myocardial autophagic flux, which resulted in cardiomyocyte death and cardiac dysfunction. And other studies demonstrated that β 1 ‐AA induced the decrease of AMPK phosphorylation, the key hub of autophagy pathway, while adiponectin up‐regulated autophagic flux mediated by AMPK. However, it is not clear whether adiponectin improves the inhibition of myocardial autophagic flux induced by β 1 ‐AA by up‐regulating the level of AMPK phosphorylation. In this study, it has been confirmed that β 1 ‐AA induced the decrease of AMPK phosphorylation level in both vivo and vitro. Moreover, pretreatment of cardiomyocytes with AMPK inhibitor Compound C could further reduce the autophagic flux induced by β 1 ‐AA. Adiponectin deficiency could aggravate the decrease of myocardial AMPK phosphorylation level, autophagic flux and cardiac function induced by β 1 ‐AA. Further, exogenous adiponectin could reverse the decline of AMPK phosphorylation level and autophagic flux induced by β 1 ‐AA and even reduce cardiomyocyte death. While pretreated with the Compound C, the adiponectin treatment did not improve the decreased autophagosome formation, but still improved the decreased autophagosome clearance induced by β 1 ‐AA in cardiomyocytes. This study is the first time to confirm that β 1 ‐AA could inhibit myocardial autophagic flux by down‐regulating AMPK phosphorylation level. Adiponectin could improve the inhibition of myocardial autophagic flux induced by β 1 ‐AA partly dependent on AMPK, so as to provide an experimental basis for the treatment of patients with β 1 ‐AA‐positive cardiac dysfunction.