Cardioprotective Effects of 3-Phosphoinositide-Dependent Protein Kinase-1 on Hypoxic Injury in Cultured Neonatal Rat Cardiomyocytes and Myocardium in a Rat Myocardial Infarct Model

  • SHIM Tae-Jin
    Department of Internal Medicine, College of Medicine, Chungbuk National University College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University
  • BAE Jang-Whan
    Department of Internal Medicine, College of Medicine, Chungbuk National University
  • KIM Yeon-Jung
    Department of Internal Medicine, College of Medicine, Chungbuk National University
  • KIM Dae Joong
    College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University
  • HWANG Kyung-Kuk
    Department of Internal Medicine, College of Medicine, Chungbuk National University
  • KIM Dong-Woon
    Department of Internal Medicine, College of Medicine, Chungbuk National University
  • CHO Myeong-Chan
    Department of Internal Medicine, College of Medicine, Chungbuk National University

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3-Phosphoinositide-dependent protein kinase-1 (PDK1) is involved in numerous cellular responses. In this study, we investigated the protective effects of PDK1 gene expression against hypoxic conditions in cultured rat CMCs (rCMCs) and in a rat myocardial infarction (MI) model using the lentiviral vector (LeV) system. LeV-PDK1 transfer effectively reduced the apoptotic cell death caused by hypoxic injury as compared to LeV-GFP transfer in rCMCs the expression of survival proteins increased in the LeV-PDK1 group, whereas apoptosis signaling decreased in the rCMCs and in infarcted hearts treated with LeV-PDK1. LeV-PDK1 transfer also reduced apoptosis and infarct size and attenuated myocardial wall thinning and ventricular remodeling in a rat MI model. These findings suggest that PDK1 has a protective role in the injured ischemic myocardium via overexpression of the cell survival pathway in CMCs. Hence PDK1 can be used as a treatment strategy for myocardial salvage inin hypoxic injury.

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