Adiponectin up-regulates the decrease of myocardial autophagic flux induced by β 1 -adrenergic receptor autoantibody partly dependent on AMPK.

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.
(© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)