Expression of TGF-beta1 in smooth muscle cells regulates endothelial progenitor cells migration and differentiation

Abstract

Objective: Endothelial angiogenesis in the intima of the arterial wall is one of key events in the pathogenesis of arteriosclerosis. The molecular mechanisms by which transforming growth factor beta 1 (TGFbeta1) and endothelial progenitor cells may be responsible for angiogenesis of arteriosclerosis lesions are poorly understood.

Materials and methods: Primary culture smooth muscle cells were transfected with pMAMneoTGFbeta1. ELISA checked VEGF expression in smooth muscle cells. Human EPCs (CD34+ cells) were cultured in pMAMneoTGFbeta1 or pMAMneo transfected smooth muscle cells conditional medium. After 21 days, differentiated endothelial colonies were confirmed by immunofluorescence for von Willebrand factor (vWF) and vascular-endothelial (VE)-cadherin. The VEGFR-1 expression in differentiated endothelial colonies was detected by ELISA. Cells migration and adhesion toward pMAMneoTGFbeta1 and pMAMneo transfected smooth muscle cells were also measured in parallel flow chamber.

Results: Abundant TGFbeta1 stable expressed in smooth muscle cells. TGFbeta1 transfected smooth muscle cells expressed significantly higher level VEGF than pMAMneo group. As judged by positive staining for endothelial markers vWF and VE-cadherin, the combination of TGFbeta1 transfected smooth muscle cells conditional medium produced significantly more endothelial colonies (P<0.05) than did pMAMneo group. The adhesion force between endothelial progenitor cells and smooth muscle cells in TGFbeta1 group was higher than control.

Conclusion: TGFbeta1 expressed smooth muscle cells can be helpful for increasing endothelial progenitor cells adhesion and differentiation. It may be responsible for angiogenesis of arteriosclerosis lesions and useful for blood vessel tissue engineering.