MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6. (27th February 2014)

• Record Type: Journal Article
• Authors: Wang, Xiaohui; Ha, Tuanzhu; Zou, Jianghuan; Ren, Danyang; Liu, Li; Zhang, Xia; Kalbfleisch, John; Gao, Xiang; Williams, David; Li, Chuanfu
• Is Part Of: Cardiovascular research. Volume 102:Number 3(2014)
• Page Start: 385
• Page End: 395
• Publication Date: 2014-02-27
• Subjects: MicroRNA-125b -- Myocardial I/R -- NF-κB -- Apoptosis -- p53; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvu044
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Aims: The present study examined the role of microRNA-125b (miR-125b) in myocardial ischaemia/reperfusion (I/R) injury. We constructed lentivirus-expressing miR-125b (LmiR-125b) and developed transgenic mice with overexpression of miR-125b. Methods and results: LmiR-125b was transfected into mouse hearts through the right common carotid artery. Lentivirus vector (LmiR-Con) served as vector control. Untreated mice served as I/R control. Sham operation served as sham control. Seven days after transfection, the hearts were subjected to ischaemia (45 min) followed by reperfusion (4 h). Myocardial infarct size was analysed by 2, 3, 5-triphenyltetrazolium chloride staining. In separate experiments, hearts were subjected to ischaemia (45 min) followed by reperfusion for up to 7 days. Cardiac function was measured by echocardiography before, as well as 3 and 7 days after myocardial I/R. Increased expression of miR-125b significantly decreased I/R-induced myocardial infarct size by 60% and prevented I/R-induced decreases in ejection fraction (EF%) and fractional shortening (%FS). Transgenic mice with overexpression of miR-125b also showed the protection against myocardial I/R injury. Increased expression of miR-125b attenuated I/R-induced myocardial apoptosis and caspase-3/7 and -8 activities. Western blot showed that increased expression of miR-125b suppresses p53 and Bak1 expression in the myocardium. In addition, transfection of LmiR-125b decreased the levels of TNF receptor-associated factor 6 (TRAF6) and prevented I/R-induced NF-κB activation. Conclusion: miR-125 protects the myocardium from I/R injury by preventing p53-mediated apoptotic signalling and suppressing TRAF6-mediated NF-κB activation.