Suppression of microRNA-16 protects against acute myocardial infarction by reversing beta2-adrenergic receptor down-regulation in rats.

Abstract

microRNA-16 (miR-16) has been shown to be up-regulated in ischemic heart. Beta2-adrenoreceptor (β2-AR) exerts cardioprotective property in ischemic injury. This study aims to determine the effect of miR-16 in cardiac injury in rats and the possible involvement of β2-AR in this process. Acute myocardial infarction (AMI) model in rats was induced by ligation of left coronary artery. Neonatal rat ventricular cells (NRVCs) were cultured in vitro tests. The cardiomyocyte model of oxidative injury was mimicked by hydrogen peroxide. The expression of miR-16 was obviously up-regulated and β2-AR was remarkably down-regulated in both AMI rats and NRVCs under oxidative stress. miR-16 over-expression in NRVCs reduced cell viability and increased apoptosis. Conversely, inhibition of endogenous miR-16 with its specific inhibitor reversed these changes. Over-expression of miR-16 using an miR-16 lentivirus in AMI rats markedly increased cardiac infarct area, lactate dehydrogenase and creatine kinase activity, and exacerbated cardiac dysfunction. Lentivirus-mediated knockdown of miR-16 alleviated acute cardiac injury. Moreover, miR-16 over-expression significantly suppressed β2-AR protein expression in both cultured NRVCs and AMI rats, while inhibition of miR-16 displayed opposite effect on β2-AR protein expression. Luciferase assay confirmed that miR-16 could directly target the 3'untranslated region of β2-AR mRNA. miR-16 is detrimental to the infarct heart and suppression of miR-16 protects rat hearts from ischemic injury via up-regulating of β2-AR by binding to the 3'untranslated region of β2-AR gene. This study indicates that targeting miR-16/β2-AR axis may be a promising strategy for ischemic heart disease.

• Authors: Jiaqi Liu, Fei Sun, Yuying Wang, Wanqi Yang, Hongwen Xiao, Yue Zhang, Renzhong Lu, Haixia Zhu, Yuting Zhuang, Zhenwei Pan, Zhiguo Wang, Zhimin Du, Yanjie Lu
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 12 Pg. 20122-20132 (Mar 21 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28423616 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• MIRN16 microRNA, rat
• MicroRNAs
• Protective Agents
• Receptors, Adrenergic, beta-2

Topics

• 3' Untranslated Regions (genetics)
• Acute Disease
• Animals
• Apoptosis
• Cell Proliferation
• Cells, Cultured
• Down-Regulation
• Male
• MicroRNAs (genetics)
• Myocardial Infarction (genetics, metabolism, pathology, prevention & control)
• Myocardium (cytology, metabolism)
• Protective Agents
• Rats
• Rats, Sprague-Dawley
• Receptors, Adrenergic, beta-2 (chemistry, genetics, metabolism)