Shear stress and interleukin-8 (IL-8) on the proliferation, differentiation and tube formation of endothelial progenitor cells (EPCs)

Abstract

Endothelial progenitor cells (EPCs) derived from bone marrow, are also found in circulation and involved in both tumor vasculogenesis and wound healing. During the process of EPCs incorporation into tissues and neovascularization, the cells are exposed to fluid shear stress. Interleukin-8 (IL-8) has been shown to play an important role in tumor growth, angiogenesis and metastasis. In our previous study, IL-8 gene expression of cultured human umbilical vein endothelial cells was significantly increased after stimulation by low shear stress for 1 to 2 h. Hence, there may be some connection between the IL-8 and shear stress in the EPCs incorporation into tissues and neovascularization. This study aimed to investigate whether the shear stress and IL-8 played important role in this process. After the cells were pretreated by shear stress, the cells were stimulated by IL-8, and then the expressions of CD133, VWF, VE-cadherins and VEGFR-2 in EPCs were measured. The proliferation, apoptosis, cell cycle, migration and tube formation of EPCs were detected after the cells expose to shear stress stimulated by IL-8. Results show that IL-8 or shear stress alone can induce EPCs proliferation decreased. 5 and 10 dyne/cm² shear stress can both induce EPCs differentiation into the mature ECs. The shear stress of 10 dyne/cm² on the EPCs developed an extensive tubular network than that of cells stimulated by IL-8 alone, but the shear stress of 5 dyne/cm² depressed the tube formation ability. From the result of transwell assay, shear stress of 10 dyne/cm² enhanced the EPCs cell migration stimulated by IL-8, while shear stress of 5 dyne/cm² decreased it. In addition, the shear stress of 10 dyne/cm² induced an increase in wound healing. These findings suggest that EPCs are sensitive to shear stress. Both shear stress and IL-8 can influence the process of EPCs repair in wound. Also, high shear stress (10 dyne/cm²) combined with IL-8 can induce the differentiation of EPCs to more matured endothelial cells.

Key words: Shear stress, interleukin-8 (IL-8), endothelial progenitor cells (EPCs).