Apocynin attenuates diabetic cardiomyopathy by suppressing ASK1-p38/JNK signaling

Abstract

Diabetic cardiomyopathy (DCM) significantly increased the morbidity of heart failure in diabetic patients. Long-time oxidative stress is an indisputable contributor for DCM development. Apocynin (APO) has been suggested to be a potential drug against oxidative stress. The study aims to find out the effects of APO on DCM and the related mechanisms. Mice were randomly divided into four groups: control (CON), APO, DCM and DCM + APO. Echocardiography analyses, histological analyses, Western blot and RT-PCR were used to explore the roles and mechanisms of APO in DCM. Isolated neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) were used for further confirming the APO treatment effects in vitro. Deteriorated cardiac function, enlarged cardiomyocytes, excess cardiac fibrosis and significant cardiac oxidative stress were observed in DCM group. However, APO treatment successfully improved cardiac function, decreased cardiac hypertrophy and fibrosis, and depressed oxidative stress. Mechanistically, APO treatment markedly suppressed apoptosis signal regulating kinase 1(ASK1)-p38/c-jun N-terminal kinase (JNK) signaling and reduced apoptosis. It also inhibited NRCM apoptosis and CF activation via depressing ASK1-p38/JNK signaling in vitro. Moreover, adenovirus-mediated ASK1 overexpression completely removed the protection of APO in vitro. In conclusion, APO treatment could effectively attenuate DCM-associated injuries in vivo and protect against high glucose-induced NRCM and CF injuries in vitro via suppressing ASK1-p38/JNK signaling. APO might be a potential ASK1 inhibitor for treating DCM.