Attenuation of Cardiac Dysfunction and Remodeling of Myocardial Infarction by microRNA-130a are Mediated by Suppression of PTEN and Activation of PI3K Dependent Signaling
Document Type
Article
Publication Date
12-1-2015
Description
Objective: Activation of PI3K/Akt signaling protects the myocardium from ischemia/reperfusion injury. MicroRNAs have been demonstrated to play an important role in the regulation of gene expression at the post-transcriptional level. In this study, we examined whether miR-130a will attenuate cardiac dysfunction and remodeling after myocardial infarction (MI) via PI3K/Akt dependent mechanism. Approaches and results: To determine the role of miR-130a in the proliferation and migration of endothelial cells, HUVECs were transfected with miR-130a mimics before the cells were subjected to scratch-induced wound injury. Transfection of miR-130a mimics stimulated the migration of endothelial cells into the wound area and increased phospho-Akt levels. To examine the effect of miR-130a on cardiac dysfunction and remodeling after MI, Lentivirus expressing miR-130a (LmiR-130a) was delivered into mouse hearts seven days before the mice were subjected to MI. Cardiac function was assessed by echocardiography before and for up to 21 days after MI. Ejection fraction (EF%) and fractional shortening (FS%) in the LmiR-130a transfected MI hearts were significantly greater than in LmiR-control and untransfected control MI groups. LmiR-130a transfection increased capillary number and VEGF expression, and decreased collagen deposition in the infarcted myocardium. Importantly, LmiR-130a transfection significantly suppressed PTEN expression and increased the levels of phosphorylated Akt in the myocardium. However, treatment of LmiR-130a-transfected mice with LY294002, a PI3K inhibitor, completely abolished miR-130a-induced attenuation of cardiac dysfunction after MI. Conclusions: miR-130a plays a critical role in attenuation of cardiac dysfunction and remodeling after MI. The mechanisms involve activation of PI3K/Akt signaling via suppression of PTEN expression.
Citation Information
Lu, Chen; Wang, Xiaohui; Ha, Tuanzhu; Hu, Yuanping; Liu, Li; Zhang, Xia; Yu, Honghui; Miao, Jonathan; Kao, Race; Kalbfleisch, John; Williams, David; and Li, Chuanfu. 2015. Attenuation of Cardiac Dysfunction and Remodeling of Myocardial Infarction by microRNA-130a are Mediated by Suppression of PTEN and Activation of PI3K Dependent Signaling. Journal of Molecular and Cellular Cardiology. Vol.89 87-97. https://doi.org/10.1016/j.yjmcc.2015.10.011 PMID: 26458524 ISSN: 0022-2828