Improve Cardiac Systolic Function By Integrin-linked Kinase Overexpression In Myocardial Infarction Rat Partly Mediated Through Reduced Cardiomyocyte Apoptosis

Objective: Left ventricular (LV) remodeling is frequently associated with the development of heart failure in patients with myocardial infarction. Cardiomyocyte apoptosis may play a causal role in the LV remodeling. Integrin-linked kinase (ILK), a serine/threonine (Ser/Thr) protein kinase, was discovered in 1996. ILK is a crucial regulatory factor in the cell-extracellular matrix interaction which is relative with cell survival. In the present study, we investigated whether ILK may reduce the cardiomyocyte apoptosis and regulate LV function after myocardial infarction.Methods: Adenoviral vector expressing ILK or empty adeno-null was directly injected into rat peri-infarct myocardium following left anterior descending coronary artery ligation. ILK expression was confirmed by western blotting. Echocardiographic analysis was performed 4 weeks after viral delivery to determine LV dimension, LV wall thickness and percent LV fractional shortening (%FS). TUNEL analysis and the activation of caspase-3 (western blotting) were determined as indicators of cardiomyocyte apoptosis.Results: Echocardiographic demonstrated relatively preserved cardiac function in the ILK group (%FS:46.01±5.71 VS 40.93±5.81,P<0.05). ILK treatment was associated with preservation of LV geometry (LVEDD:6.93±0.76 VS 7.82±1.06,P<0.05;LVESD:3.77±0.75 VS 4.62±0.79,P<0.05). TUNEL analysis revealed a reduction in apoptosis in the ILK group both in border zone (0.1866±0.0328 VS 0.3613±0.0841,P<0.05) and the remote zone (0.1049±0.0367 VS 0.2429±0.0445,P<0.05) of MI. The activity of caspase-3 in the ILK group also decreased significantly compared to controls.Conclusions: ILK gene therapy improves cardiac remodeling and systolic function in rats following myocardial infarction, and this effects, at least partly, mediated through reduced cardiomyocyte apoptosis.