[Bone marrow mesenchymal cell transplantation reduces left ventricular remodeling in heart failure following acute myocardial infarction].
OBJECTIVE
Bone marrow mesenchymal cell (MSC) transplantation has been shown to improve heart failure but the mechanism and the subsequent effects are unclear. We tested the hypothesis that MSC transplantation reduces left ventricular remodeling through the MMP/TIMP system in heart failure following acute myocardial infarction.


METHODS
Female SD rats underwent coronary artery ligation to induce myocardial infarction. Four weeks later, the rats were divided into the test group (n = 7) and the control group (n = 7), respectively. The donor MSCs were harvested and expanded from male SD rats (5 x 10(6) in 50 microl PBS) and injected into the ischemic myocardium, while the control group received the same volume of PBS. Left ventricular morphology was then evaluated in both groups through staining with H&E and Masson's trichrome. Immunohistochemical staining was used to examine the expressions of MMP2 and TIMP1, as well as type I and type III collagens, in the scar zones. The protein levels of MMP2 and TIMP1 were determined by Western blotting.


RESULTS
MSC differentiated into fibroblast-like cells at 21 days after transplantation in the test group. In addition, many inflammatory cells infiltrated and aggregated in the scar area, but this effect was reduced at day 7 after transplantation. The following changes were noted in the test group compared to the control group: ejection fraction and shortening fraction were higher [(63.43 +/- 3.97)% vs. (36.20 +/- 3.99)%, (31.71 +/- 1.98)% vs. (18.00 +/- 2.07)%, P < 0.05]; dp/dt(min) was reduced [(-4756.24 +/- 270.00) mm Hg/s vs. -2789.53 +/- 624.13) mm Hg/s, P < 0.05]; the left ventricular thinning ratio was significantly higher [(76.34 +/- 2.66)% vs. (64.37 +/- 2.36)%, P < 0.05]; the infarct size was smaller [(36.19 +/- 0.83)% vs. (42.12 +/- 1.88)%, P < 0.05]; type I collagen expression in the scar area was much higher; type III collagen expression was much lower; MMP2 expression was reduced and TIMP1 expression was increased.


CONCLUSIONS
MSC transplantation led to dynamic changes in the collagen network through regulation of MMP2/TIMP1 system and consequently interrupted the progress of adverse LV remodeling in heart failure following acute myocardial infarction.
Guo
Yu-tao
YT
Department of Geriatric Cardiology, General Hospital of the Chinese PLA, Beijing 100853, China.
Li
Xiao-ying
XY
Wu
Di
D
Yao
Ke-qun
KQ
Chen
Ping
P
Ma
Kang-tao
KT
Zhou
Chun-yan
CY
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000601:surgery; D011480:Protease Inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020778:Matrix Metalloproteinase 2