The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression

Endothelial cells lining the walls of blood vessels are exposed simultaneously to wall shear stress (WSS) and circumferential stress (CS) that can be characterized by the temporal phase angle between WSS and CS (stress phase angle-SPA). Regions of the circulation with highly asynchronous hemodynamics (SPA close to -180 degrees) such as coronary arteries are associated with the development of pathological conditions such as atherosclerosis and intimal hyperplasia whereas more synchronous regions (SPA closer to 0 degrees) are spared of disease. The present study evaluates endothelial cell gene expression of 42 atherosclerosis-related genes under asynchronous hemodynamics (SPA=-180 degrees) and synchronous hemodynamics (SPA= 0 degrees). This study used a novel bioreactor to investigate the cellular response of bovine aortic endothelial cells (BAECS) exposed to a combination of pulsatile WSS and CS at SPA= 0 or SPA=-180. Using a PCR array of 42 genes, we determined that BAECS exposed to non-reversing sinusoidal WSS (10 +/- 10 dyne/cm(2)) and CS (4 +/- 4 %) over a 7 hour testing period displayed 17 genes that were up regulated by SPA = -180 degrees, most of them proatherogenic, including NF kappa B and other NF kappa B target genes. The up regulation of NF kappa B p50/p105 and p65 by SPA =-180 degrees was confirmed by Western blots and immunofluorescence staining demonstrating the nuclear translocation of NF kappa B p50/p105 and p65. These data suggest that asynchronous hemodynamics (SPA=-180 degrees) can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA may be an important parameter characterizing arterial susceptibility to disease.