Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction.
OBJECTIVE
This study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction.


METHODS
Forty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson's trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis.


RESULTS
The fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group, ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4 groups.


CONCLUSIONS
Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.
Wang
Jian-an
JA
Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. wang_jian_an@tom.com
Luo
Rong-hua
RH
Zhang
Xing
X
Xie
Xiao-jie
XJ
Hu
Xin-yang
XY
He
Ai-na
AN
Chen
Jie
J
Li
Jia-hui
JH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000201:enzymology; D020913:Perindopril / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D020257:Ventricular Remodeling
D000806:Angiotensin-Converting Enzyme Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020913:Perindopril