Expression of integrin-linked kinase improves cardiac function in a swine model of myocardial infarction.

Abstract

Previous studies have described the beneficial effects of overexpressing integrin-linked kinase (ILK) after myocardial infarction (MI) in small animal models. However, the effects of ILK in pre-clinical large animals are not known. To move closer to clinical translation, we examined the effects of ILK gene transfer in a swine model of ischemic heart disease. Swine received percutaneous intracoronary injections of adenoviral vector expressing ILK (n=10) or empty ad-null (n=10) in the left anterior descending coronary artery (LAD) following LAD occlusion. Four weeks after transfection, we confirmed that transgene expression was restricted to the infarcted area in the cardiac tissue. Imaging studies demonstrated preserved cardiac function in the ILK group. ILK treatment was associated with reduced infarcted scar size and preserved left ventricular (LV) geometry (LV diameter and LV wall thickness). Enhanced angiogenesis was preserved in the ILK animals, along with reduction of apoptosis. ILK gene therapy improves cardiac remodeling and function in swine following MI associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation with no signs of toxicity. These results may deliver a new approach to treat post-infarct remodeling and subsequent heart failure.