Attenuation of cardiac dysfunction and remodeling of myocardial infarction by microRNA-130a is mediated by suppression of PTEN and activation of PI3K dependent signaling

Autor: Xia Zhang, Chen Lu, Race L. Kao, Yuanping Hu, Tuanzhu Ha, Honghui Yu, John Kalbfleisch, Xiaohui Wang, Chuanfu Li, David B. Williams, Li Liu, Jonathan Miao
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Male
Vascular Endothelial Growth Factor A
Cardiotonic Agents
Ischemia
Myocardial Infarction
Apoptosis
Myocardial Reperfusion Injury
Ligands
Transfection
Article
Phosphatidylinositol 3-Kinases
Cell Movement
medicine
Human Umbilical Vein Endothelial Cells
PTEN
Animals
cardiovascular diseases
Myocardial infarction
Phosphorylation
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Regulation of gene expression
biology
business.industry
Myocardium
Lentivirus
Toll-Like Receptors
PTEN Phosphohydrolase
Heart
medicine.disease
Enzyme Activation
Mice
Inbred C57BL
MicroRNAs
Microvessels
cardiovascular system
Cancer research
biology.protein
Matrix Metalloproteinase 2
Collagen
Signal transduction
Cardiology and Cardiovascular Medicine
business
Reperfusion injury
Proto-Oncogene Proteins c-akt
Signal Transduction
Popis: 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.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.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.
Databáze: OpenAIRE
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