ADAR2 increases in exercised heart and protects against myocardial infarction and doxorubicin-induced cardiotoxicity

Exercise training benefits the heart. The knowledge of posttranscription regulation, especially RNA editing, in hearts remain rare. ADAR2 is an enzyme that edits adenosine to inosine nucleotides in double-stranded RNA, and RNA editing is associated with many human diseases. We found that ADAR2 was upregulated in hearts during exercise training. AAV9-mediated cardiac-specific ADAR2 overexpression attenuated acute myocardial infarction (AMI), MI remodeling, and pression of ADAR2 inhibited DOX-induced cardiomyocyte (CM) apoptosis. but it could also induce neonatal rat CM proliferation. Mechanistically, ADAR2 could regulate the abundance of mature miR-34a in CMs. Regulations of miR-34a or its target genes (Sirt1, Cyclin D1, and Bcl2) could affect the pro-proliferation and anti-apoptosis effects of ADAR2 on CMs. These data demonstrated that exercise-induced ADAR2 protects the heart from MI and DOX-induced cardiotoxicity. Our work suggests that ADAR2 overexpression or a post-transcriptional associated RNA editing via ADAR2 may be a promising therapeutic strategy for heart diseases.

Automated summary

Exercise training benefits the heart and upregulates ADAR2 expression in the heart. ADAR2 can regulate the abundance of mature miR-34a in cardiomyocytes and affect their proliferation and apoptosis. This study suggests that ADAR2 overexpression or RNA editing via ADAR2 may be a promising therapeutic strategy for heart diseases.