Effects of transplantation of tissue inhibitor-3 of matrix metalloproteinase gene-transfected vascular smooth muscle cells on heart structure and function after myocardial infarction

AIM: To investigate the effects of transplantation of tissue inhibitor-3 of matrix metalloproteinase (TIMP-3) gene-transfected vascular smooth muscle cells (VSMCs) on heart structure and function after myocardial infarction (MI) in rats. METHODS: VSMCs were obtained from rat thoracic aorta by tissue-piece inoculation. TIMP-3 gene was transfected into VSMCs by lipidosome-mediated method. One hundred and twenty-one female Wistar rats, aged 12 weeks and weighing between 200 and 250 g, were prepared. Acute MI models were established in 93 rats by ligating the descending left coronary artery; 84 survived and were divided randomly into three groups (n=28). Three days after MI, rat chests were opened again and 0.3 ml Dulbecco’s modified Eagle’s medium (DMEM) containing 3×106 TIMP-3 gene-transfected VSMCs (group A), 3×106 VSMCs (group B) or 0.3 ml DMEM (group C) was immediately injected into the infarcted myocardium. The control group (group D) consisted of 28 rats without any treatment. Heart function was detected by ultrasonic echocardiogram. Heart samples were harvested and heart left ventricular volume and volume index were measured. Heart structure was also observed by tissue morphologic examination. RESULTS: VSMCs were cultivated and had a high purity (98%). TIMP-3 gene was transfected into VSMCs successfully. Four weeks after gene transfer, heart function in group A was improved over group B and group C (P<0.05), group B was improved over group C (P<0.05), but they were all poorer than group D (P<0.05. Left ventricular volume was (94.4±158.3) mm3, (1 126.5±284.7) mm3, (1 372.8±181.9) mm3 and (420.2±39.6) mm3 in the four groups, and volume index was (2.957±0.362) mm3/g, (3.604±0.710) mm3/g, (4.538±0.259) mm3/g and (1.009±0.134) mm3/g. The results of histological observation showed MI in group C. Clustering muscle cells were seen in infarction field in group B and heart ventricle wall was thicker than in group C. Infarction field in group A was smaller than in groups B and C. Heart ventricle wall in group A was thicker than in groups B and C. CONCLUSION: Implanted TIMP-3 gene transfected VSMCs in infarcted myocardium at 3 days after acute MI noticeably improves heart structure and function in rats.