| First Author | Bayoumi AS | Year | 2018 |
| Journal | J Mol Cell Cardiol | Volume | 114 |
| Pages | 72-82 | PubMed ID | 29122578 |
| Mgi Jnum | J:257500 | Mgi Id | MGI:6115212 |
| Doi | 10.1016/j.yjmcc.2017.11.003 | Citation | Bayoumi AS, et al. (2018) A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes. J Mol Cell Cardiol 114:72-82 |
| abstractText | BACKGROUND: Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy, and has been proposed as a biomarker of heart failure. We previously reported that the beta-blocker carvedilol promotes cardioprotection via beta-arrestin-biased agonism of beta1-adrenergic receptor while stimulating miR-125b-5p processing in the mouse heart. We hypothesize that beta1-adrenergic receptor/beta-arrestin1-responsive miR-125b-5p confers the improvement of cardiac function and structure after acute myocardial infarction. METHODS AND RESULTS: Using cultured cardiomyocyte (CM) and in vivo approaches, we show that miR-125b-5p is an ischemic stress-responsive protector against CM apoptosis. CMs lacking miR-125b-5p exhibit increased susceptibility to stress-induced apoptosis, while CMs overexpressing miR-125b-5p have increased phospho-AKT pro-survival signaling. Moreover, we demonstrate that loss-of-function of miR-125b-5p in the mouse heart causes abnormalities in cardiac structure and function after acute myocardial infarction. Mechanistically, the improvement of cardiac function and structure elicited by miR-125b-5p is in part attributed to repression of the pro-apoptotic genes Bak1 and Klf13 in CMs. CONCLUSIONS: In conclusion, these findings reveal a pivotal role for miR-125b-5p in regulating CM survival during acute myocardial infarction. |
