Background and Objectives: Protections of cardiomyocytes (CMCs) from noxious injuries are important therapeutic targets in heart diseases. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been implicated in numerous cellular processes especially related with malignancy and survival signals. Very scarce data of PDK-1 in cardiovascular research field exist. Therefore, we investigated the effects of PDK1 in hypoxic injured CMCs and in the rat myocardial infarction (MI).
Methods: To achieve efficient and sustained gene expression and transfer, we used Lentiviral vector system. In vitro, rCMCs (5��10⁵cells) were infected by Lentiviral-PDK1 or GFP (1.5��107IU) then left in hypoxic condition for 24 hours. CMCs were examined by FACS and western blot to know the survival signal. In vivo, Lentiviral-PDK1 or GFP was injected in vicinity of rat MI tissue generated by coronary artery ligation for 2 weeks (wks). After 2 wks, Masson's trichrome stain, western blot, IHC were performed with collected hearts.
Results: In Lentiviral-PDK1 group, apoptosis and expression of caspase-3, p53 was decreased, expressions of PDK1, pAkt/Akt, pGSK-3棺/GSK-3棺, Bcl-2/Bax were increased compared to control group. Also infarction size (6.41짹2.75 vs 12.01짹1.48 mm², p<0.05) of Lentiviral-PDK1 group reduced, and myocardial volume (70.4짹3.0 vs 57.8짹8.9 mm², p<0.05) and myocardial thickness (2883.37짹252.6 vs 1999.8짹430.8 ���) increased than control group (Fig.). In IHC for Lentiviral-PDK1 group, expression of PDK1 increased, and expression of p53 and caspase-3 decreased.
Conclusion: These experiments results proved the PDK1 signaling plays an important role in regulating cardiac viability. It suggests the PDK1 is one of the candidates for ischemic protection of myocardium.