Stretch and Shear Interactions Affect Intercellular Junction Protein Expression and Turnover in Endothelial Cells

Complex hemodynamics plays a role in the localization and development of atherosclerosis. Endothelial cells (ECs) lining blood vessel walls are directly influenced by various hemodynamic forces: simultaneous wall shear stress (WSS), normal stress, and circumferential stress/strain (CS) due to pulsatile flow, pressure, and diameter changes. ECs sense and transduce these forces into biomolecular responses that may affect intercellular junctions. In this study, a hemodynamic simulator was used to investigate the combined effects of WSS and CS on EC junctions with emphasis on the stress phase angle (SPA), the temporal phase difference between WSS and CS. Regions of the circulation with highly negative SPA, such as the coronary arteries and carotid bifurcation, are more susceptible to the development of atherosclerosis. At 5 h, expression of the tight junction (TJ) protein zonula occludens-1 was significantly higher for the atheroprotective SPA = 0A degrees compared to the atherogenic SPA = -180A degrees while the apoptosis rate was significantly higher for SPA = -180A degrees than SPA = 0A degrees. This decrease in TJ protein and increase in apoptosis and associated leaky junctions suggest a decreased junctional stability and a higher paracellular permeability for atherogenic macromolecules for the atherogenic SPA = -180A degrees compared to SPA = 0A degrees.