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 BMMSCSHH (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.