Cardioprotective role of cardiotrophin-1 gene transfer in a murine model of myocardial infarction

Abstract

We observed the effect of cardiotrophin-1 (CT-1) gene transfer on cardiomyocytes in a murine model of myocardial infarction. Sixty male CD-1 mice weighing approximately 40 g were used in the study. Forty mice were subjected to left coronary artery ligation and randomized to receive AdCT-1 vector (treated group) or AdLacZ vector (control group) treatment, with 20 mice for each group. AdCT-1 or AdLacZ vector was directly injected into the border zone of the ischemic myocardium at six sites, 10 min after ligation (10 μl/site, 2.5 × 10⁶ PFU/100 μl). Twenty mice undergoing thoracotomy and injection of an equal volume of phosphate-buffered saline solution but not coronary ligation served as sham group. Hemodynamics, histopathology and cardiomyocyte apoptosis were detected at 2 weeks after injection. Four animals in sham, nine in control, and six in treated groups died during the experiment. The remaining 41 mice were included in the study. Mean arterial pressure, left ventricular systolic pressure, and the maximum rate of left ventricular pressure rise or fall were significantly higher in treated group than in control group (P < 0.01 for all), whereas left ventricular end-diastolic pressure, infarct size, the ratio of right ventricle or lung weight to body weight, and apoptotic index were significantly lower in treated group than in control group (P < 0.01 for all). The caspase-3 activation and mitochondrial cytochrome c release were also lower in treated group than in control group (P < 0.01 for each). AdCT-1 injection significantly inhibited Fas, Bax and p53, and increased CT-1 and Bcl-2 expression in myocardium. Our results suggest that AdCT-1 vector can be effectively transfected and continued to express bioactive CT-1 protein in myocardium. CT-1 plays an important cardioprotective effect on myocardial damage in the murine model of myocardial infarction.

• Myocardial infarction
• cardiotrophin-1
• gene transfer
• apoptosis