Shear Stress Modulates Endothelial VCAM-1 Expression via Endoplasmic Reticulum Stress Response Pathways

IntroductionComplications from atherosclerosis remain the leading cause of death and disability in the U.S. This inflammatory disease is characterized by the accumulation of lipid-rich plaques within the artery wall at predictable locations, which correlate strongly with the local arterial geometry and associated hemodynamic environment, notably low magnitude and reversing fluid shear stress (SS). Mechano-responsive endothelial cells (EC) moderate vascular inflammation, including cell adhesion molecule (CAM) presentation and subsequent leukocyte recruitment. Endoplasmic reticulum (ER) stress and associated responses have emerged as signaling pathways linking cellular stress to inflammation and cardiovascular risk. Chronic activation of the ER stress response in endothelium has been observed in regions of disturbed flow in the arteries of lesion free swine, and in response to disturbed flow in cultured EC, demonstrating its importance as a possible signature of endothelial dysfunction and atherosusceptibil...