Cardioprotective Effect by Adenovirus-mediated Protein Kinase C-ε Gene Transfer to Myocardium of Mouse

Objective Protein kinase C-epsilon （PKC ε） transgenic mice exhibit inherent cardioprotection against myocardial ischemia-reperfusion injury. The present study aims to investigate the role of the adenovirus-mediated PKC ε gene transfer to myocardium of adult mouse on myocardial ischemia-reperfusion insult. Methods Recombinant adenovirus expressing rabbit PKC ε gene was generated by cloning PKC ε cDNA into E1 region of human adenoviral type 5 genomic DNA. 3.3×1010 plaque forming units （pfu）/kg body weight of the PKC ε adenovirus were directly injected to myocardium of mice. Control mice were directly injected same dose of empty vector adenoviruses. PKC ε protein levels were determined by Western immunoblotting. Left ventricular infarction was established by 30 min of coronary occlusion followed by 24 hours of reperfusion. Infarct size analyses were performed by staining with 2, 3, 5-triphenyltetrazolium chloride and phthalo blue dye, photographing and calculating. Results PKC ε gene transfer mice were associated with a approximate 4-fold of increase in PKC ε transgene protein levels at 48 hours after direct myocardial injection when compared to control mice. There were no significant differences in heart weight, LV weight, risk area weight and percentage of risk area weight to LV weight between PKC ε gene transfer mice and control mice. However, infarct weight （35.4±3.1）mg vs （10.3±1.3） mg, percentage of infarct to risk area （51.1±0.3 vs 17.0±2.6） and percentage of infarct to LV （30.0±3.0 vs 9.2±0.5） in PKC ε gene transfer mice were reduced significantly when compared with control mice. Conclusion Adenovirus-mediated, myocardium-directed PKC ε gene transfer enhanced resistance against myocardial ischemia- reperfusion insult.