• Xuan Zhang, Long Cheng, Longhe Xu, Yunliang Zhang, Yitian Yang, Qiang Fu, Weidong Mi, and Hao Li.
• Anesthesia and Operation Centre, Chinese PLA General Hospital, Beijing, China.
• Shock. 2019 Aug 1; 52 (2): 249-256.

BackgroundIschemic postconditioning (I/Post) is an endogenous protection mechanism that reduces injury induced by ischemia-reperfusion (I/R). It remains controversial whether I/Post protects against I/R injury to the aging heart. The long non-coding RNA, H19 protects H9c2 cells against hypoxia-induced injury. This study aimed to elucidate the role of H19 in the hypoxic postconditioning (H/Post) of aged cardiomyocytes.MethodsSenescence induced by D-galactose in primary cardiomyocytes from neonatal Sprague-Dawley rats was measured by senescence-associated β-galactosidase staining. Hypoxic injury was evaluated by cell viability and apoptosis assays. H19 expression before and after hypoxia-reoxygenation (H/R) and H/Post was evaluated by real-time polymerase chain reactions. miR-29b-3p-binding sites in H19 and the cellular inhibitor of apoptosis protein 1 (cIAP1) were predicted by bioinformatics analysis, and interaction was verified by luciferase assay. The effects of altered H19, miR-29b-3p, and cIAP1 expression on the viability and apoptosis of senescent cardiomyocytes following H/Post were determined.ResultsH/Post prevented H/R injury in normal but not senescent cardiomyocytes. H19 expression was remarkably down-regulated after H/Post in senescent compared with normal cardiomyocytes. Small interfering RNA-mediated knockdown of H19 in senescent cardiomyocytes increased H/Post-induced injury. miR-29b-3p was regulated by H19 and led to a greater injury. miR-29b-3p directly targeted the 3'-untranslated region of cIAP1 and suppressed its expression. Furthermore, knockdown of cIAP1 damaged senescent cardiomyocytes following H/Post.ConclusionsThese findings suggest that H19 mediated the antiapoptotic effect of H/Post against H/R-induced injury to aged cardiomyocytes by inhibiting miR-29b-3p expression.

40 keywords...

hide…