The Influence of Cyclic and Uniform Shear Stresses Concurrent with Cyclic Stretch on the Gene Expression of Human Umbilical Vein Endothelial Cells

It has been well established that the cellular micromechanical environment plays a significant role in the behavior and function of cells. Endothelial cells, within the vasculature, are subjected to tensile and shear stresses due to pulsatile blood pressure and flow. The aim of this study was to delineate the effects of cyclic stretch concurrent with cyclic or uniform shear stresses on the gene expression of cultured human umbilical vein endothelial cells (HUVECs). Using a custom made bioreactor, two types of loadings, characterized by a 10% cyclic stretch simultaneous with a 5 dyn/cm(2) shear stress in a cyclic or uniform regimes, were applied on cells for 24 hours. The gene expression of three suggestive specific endothelial markers (ECs, FLK-1, vWF, and VE-cadherin), and two smooth muscle specific markers (alpha-SMA, SMMHC) were evaluated by real time PCR. Results indicate that both of the loading regimes, enhanced all the four endothelial markers. However loadings with a cyclic shear stress resulted in a more significant gene expression. The expression of alpha-SMA was declined, while the expression of SMMHC was augmented. Due to the substantial effect of cyclic compared to the uniform shear stress, the cyclic shear stress played a more effective role in opposing the elevation of SMMHC and significantly more effective, diminished the alpha-SMA gene expression. Results also confirmed the effect of tensile stress, especially the cyclic loading regime, on the transdifferentiation potential of endothelial cells toward smooth muscle phenotype. These findings scan be applied in the study of arterial diseases and engineering of endothelial cells for in tissue engineering purposes.