Unique Morphology and Focal Adhesion Development of Valvular Endothelial Cells in Static and Fluid Flow Environments

BACKGROUND—The influence of mechanical forces on cell function has been well documented for many different cell types. Endothelial cells native to the aortic valve may play an important role in mediating tissue responses to the complex fluid environment, and may therefore respond to fluid flow in a different manner than more characterized vascular endothelial cells. METHODS AND RESULTS—Porcine endothelial cells of aortic and aortic valvular origin were subjected to 20 dynes/cm steady laminar shear stress for up to 48 hours, with static cultures serving as controls. The aortic valve endothelial cells were observed to align perpendicular to flow, in direct contrast to the aortic endothelial cells, which aligned parallel to flow. Focal adhesion complexes reorganized prominently at the ends of the long axis of aligned cells. Valvular endothelial cell alignment was dependent on Rho-kinase signaling, whereas vascular endothelial cell alignment was dependent on both Rho-kinase and phosphatidylinositol 3-kinase signal pathways. CONCLUSIONS—These differences in response to mechanical forces suggest a unique phenotype of valvular endothelial cells not mimicked by vascular endothelial cells, and could have implications for cardiovascular cell biology and cell-source considerations for tissue-engineered valvular substitutes.