Mechanistic study of angiogenesis induced by shh-transfected BMMSC transplantation after myocardial infarction

Fenglin Song, Ming Wu, Tao Tang, Xiaoming Wu, Wenwu Zhou, Jin Shi, Wei Zhang, Zhiping Tan, Jinfu Yang

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Department of the Cardiothoracic Surgery of the 2nd Xiangya Hosptial, Central South University, Changsha, China.

DOI: 10.4236/scd.2013.32013                

Abstract

Objective: To investigate the changes and mechanism of angiogenesis in myocardium induced by transplantation of the sonic hedgehog (shh) gene transfected in bone marrow mesenchymal stem cells (BMMSC) after myocardial infarction. Methods: A rat model of acute myocardial infarction was made by coronary artery ligation. The rats were randomly divided into five groups of 40 rats each. These were further subdivided into groups of 10 rats. The peripheral regions of the infarcts were injected with either BMMSC^SHH (transfection group), equivalent BMMSC (cell only group), BMMSC and pcDNA3.1-Shh DNA mixture (mixture group), pcDNA3.1-shh DNA alone (gene only group), or equal volumes of low-sugar DMEM medium (control group). One, two, four, and eight weeks after transplantation, specimens were harvested from the transplantation site to determine the expression of SHH signaling pathway downstream genes Ptc1, Gli-2, COUP-TF II, angiogenesis promoting factor VEGF, and Ang-1 using RT-PCR. Results: Seven days after transplantation, the expression of SHH signaling pathway downstream genes, Ptc1, Gli-2, and COUP-TF II was significantly more pronounced in the transfection group than in the control group, cell only group, gene only group, or mixture group (Ptc1: P < 0.01, P < 0.01, P < 0.05, and P < 0.05, respectively; COUP-TF II: P < 0.01, P < 0.01, P < 0.05, and P < 0.05, respectively; Gli-2: P < 0.01, P < 0.01, P < 0.05, and P < 0.05, respectively). The expression of angiogenesis-promoting genes Vegf and Ang-1 was significantly more pronounced than in the control group, cell only group, or gene only group (Vegf: P < 0.01, P < 0.05, P < 0.05 respectively; Ang-1: P < 0.01, P < 0.05, and P < 0.05, respectively). Conclusion: Transplantation of the shh-gene-transfected BMMSCs to the peripheral regions of myocardial infarcts promoted angiogenesis by upregulating downstream gene expression.

Keywords

Shh ; Bone Marrow Mesenchymal Stem Cells; Ptc 1; Gli -2; COUP-TF II; VEGF; Ang -1

Conflicts of Interest

The authors declare no conflicts of interest.

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