title: Attenuation of cardiac dysfunction and remodeling of myocardial infarction by microRNA-130a are mediated by suppression of PTEN and activation of PI3K dependent signaling.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Chen
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States; Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Honghui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Miao
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States; Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Race
authors.initials: R
authors.lastname: Kao
authors.affiliation: Department of Biometry and Medical Computing, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States; Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: John
authors.initials: J
authors.lastname: Kalbfleisch
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States; Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States; Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States. Electronic address: Li@etsu.edu.
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D002316:Cardiotonic Agents / Q000378:metabolism; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D004789:Enzyme Activation; D006321:Heart / Q000503:physiopathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D016086:Lentivirus / Q000378:metabolism; D008024:Ligands; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D055806:Microvessels / Q000473:pathology; D009203:Myocardial Infarction / Q000150:complications / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D008024:Ligands; C554019:MIRN130 microRNA, human; C582652:MIRN130 microRNA, mouse; D035683:MicroRNAs; D051193:Toll-Like Receptors; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D020778:Matrix Metalloproteinase 2
keywords: Angiogenesis; MicroRNA-130a; Myocardial infarction; PI3K/Akt signaling; PTEN