Medicine and Health Sciences Commons^™

Mir15a/Mir16-1 Cluster And Its Novel Targeting Molecules Negatively Regulate Cardiac Hypertrophy., Hongchang Guo, Ke Ma, Wenjing Hao, Yao Jiao, Ping Li, Jing Chen, Chen Xu, Fu-Jian Xu, Wayne Bond Lau, Jie Du, Xin-Liang Ma, Yulin Li

Department of Emergency Medicine Faculty Papers

In response to pathological stimuli, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. miRNAs are increasingly recognized as pathogenic factors, clinically relevant biomarkers, and potential therapeutic targets. We identified that mir15a/mir16-1 cluster was negatively correlated with hypertrophic severity in patients with hypertrophic cardiomyopathy. The mir15a/mir16-1 expression was enriched in cardiomyocytes (CMs), decreased in hypertrophic human hearts, and decreased in mouse hearts after transverse aortic constriction (TAC). CM-specific mir15a/mir16-1 knockout promoted cardiac hypertrophy and dysfunction after TAC. CCAAT/enhancer binding protein (C/EBP)β was responsible for the downregulation of mir15a/mir16-1 cluster transcription. Mechanistically, mir15a/mir16-1 cluster attenuated the insulin/IGF1 …