[Effects of tissue inhibitor-3 of matrix metalloproteinases gene-transfected vascular smooth muscle cells transplantation on initial myocardium remodeling after acute myocardial infarction].
OBJECTIVE
To investigate the effects of tissue inhibitor-3 of matrix metalloproteinases (TIMP-3) gene-transfected vascular smooth muscle cells (VSMCs) transplantation on heart structure after acute myocardial infarction (AMI) in rats and to explore the potential mechanisms.


METHODS
Sixty-one female Wistar rats were produced AMI models by ligating the descending left coronary artery. Fifty-four rats were survived and divided into 3 groups randomly (n= 18): 0.5 ml PBS containing 1 x 10(6) TIMP-3 gene-transfected VSMCs (group A), 1 x 10(6) VSMCs (group B) or 0.5 ml PBS without cell(group C) were injected into the ischemic myocardium immediately. Ischemic myocardium samples were harvested at 1 week after operation. The heart structure was observed through the tissue morphologic examination. The activity of TIMP-3 gene-transfected VSMCs were measured by immunohistochemical method. Proteins of TIMP-3 and matrix metalloproteinase 9(MMP-9) were determined by Western blot.


RESULTS
VSMCs were cultivated and had a high purity (98%). TIMP-3 gene was transfected into VSMCs successfully. One week after operation in groups A, B and C, the average percentage of infarction myocardium size and left ventricle free wall area were 28.73%+/-1.56%, 39.63%+/-1.84% and 46.32%+/-2.16% separately. Group A was significantly lower than groups B and C (P<0.01), group B was significantly lower than group C (P<0.01). In groups A, B and C the average left ventricle volume indexes were 5.27+/-0.21 mm3/g, 6.69+/-0.34 mm3/g and 9.67+/-0.88 mm3/g respectively. Group A was significantly smaller than groups B and C (P<0.01), group B was significantly smaller than group C (P<0.01). The immunohistochemical observation confirmed that the implanted VSMCs and TIMP-3 gene were survival in ischemic area. The protein content of TIMP-3 in ischemic myocardium was significantly higher in group A (300 704.8+/-3 692.8) than in groups B and C (195548.8+/-3014.2, 177991.1+/-2502.1) (P<0.01), the protein content of MMP-9 in ischemic myocardium was significantly lower in group A (594827.4+/-5708.5) than in groups B and C (921461.4+/-8887.4, 1044445.0+/-8788.6) (P<0.01).


CONCLUSIONS
Implanted TIMP-3 gene transfected VSMCs in ischemic myocardium can conspicuously reduce the myocardium remodeling after AMI.
Jia
Zhibo
Z
Department of Cardiovascular Surgery, the Second Affiliated Hospital, Harbin Medical University, Harbin Heilongjiang, 150086, P. R. China. doctor_jiazhibo@yahoo.com.cn
Tian
Hai
H
Liu
Kaiyu
K
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D020257:Ventricular Remodeling
D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9