Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction

Jian-an Wang, Rong-hua Luo, Xing Zhang, Xiao-jie Xie, Xin-yang Hu, Ai-na He, Jie Chen, Jia-hui Li, Jian-an Wang, Rong-hua Luo, Xing Zhang, Xiao-jie Xie, Xin-yang Hu, Ai-na He, Jie Chen, Jia-hui Li

Abstract

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.

Conclusion: Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.

Figures

Fig. 1
Fig. 1
Biological features of cultivated bone marrow mesenchymal stem cell under inverted phase contrast microscope
Fig. 2
Fig. 2
Six weeks after implantation, DAPI-labelled (blue) MSC was detected in the ischemic portion of the myocardium
Fig. 3
Fig. 3
Masson’s trichrome staining of left ventricular tissue of rat in infraction area among 4 group (magnification, ×40). Masson’s trichrome stain was used to identify alterations of collagen in infraction area. (a) MSC+ACEI group; (b) ACEI group; (c) MSC group; (d) Control group
Fig. 3
Fig. 3
Masson’s trichrome staining of left ventricular tissue of rat in infraction area among 4 group (magnification, ×40). Masson’s trichrome stain was used to identify alterations of collagen in infraction area. (a) MSC+ACEI group; (b) ACEI group; (c) MSC group; (d) Control group
Fig. 3
Fig. 3
Masson’s trichrome staining of left ventricular tissue of rat in infraction area among 4 group (magnification, ×40). Masson’s trichrome stain was used to identify alterations of collagen in infraction area. (a) MSC+ACEI group; (b) ACEI group; (c) MSC group; (d) Control group
Fig. 3
Fig. 3
Masson’s trichrome staining of left ventricular tissue of rat in infraction area among 4 group (magnification, ×40). Masson’s trichrome stain was used to identify alterations of collagen in infraction area. (a) MSC+ACEI group; (b) ACEI group; (c) MSC group; (d) Control group
Fig. 4
Fig. 4
Expression of MMP2 and MMP9 in infraction area six weeks after implantation Lane 1: MSC+ACEI group; Lane 2: ACEI group; Lane 3: MSC group; Lane 4: Control group
Fig. 5
Fig. 5
PCR reaction product revealed by agarose gel electrophoresis (upper) and relative contents of (a) MMP2, (b) MMP9 and (c) TIMP1 mRNA to β-actin values are expressed as mean±SD (lower) M: DNA marker; Lane 1: MSC+ACEI group; Lane 2: ACEI group; Lane 3: MSC group; Lane 4: Control group
Fig. 5
Fig. 5
PCR reaction product revealed by agarose gel electrophoresis (upper) and relative contents of (a) MMP2, (b) MMP9 and (c) TIMP1 mRNA to β-actin values are expressed as mean±SD (lower) M: DNA marker; Lane 1: MSC+ACEI group; Lane 2: ACEI group; Lane 3: MSC group; Lane 4: Control group
Fig. 5
Fig. 5
PCR reaction product revealed by agarose gel electrophoresis (upper) and relative contents of (a) MMP2, (b) MMP9 and (c) TIMP1 mRNA to β-actin values are expressed as mean±SD (lower) M: DNA marker; Lane 1: MSC+ACEI group; Lane 2: ACEI group; Lane 3: MSC group; Lane 4: Control group

Source: PubMed

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