SHEAR STRESS-MEDIATED SIGNAL TRANSDUCTION

Emerging evidence shows that steady laminar flow is atheroprotective while disturbed flow creates an atheroprone environment in vivo. Chronic inflammation and reactive oxygen species production represent some of the pathogenic features of atherosclerosis formation, and it has become clear that steady laminar flow and disturbed flow or low shear stress have significant roles to modify these atherogenic events via regulating “mechanosignal transduction”. In this chapter, first we will discuss the possible pathological role of mechanosignal transduction in cardiovascular disease. Next the possible role of PECAM-1 as a mechanosensor and its regulatory mechanisms will be reviewed. Third, redox regulation induced by flow and its contribution to endothelial inflammation and apotosis will be summarized. Finally, we will discuss the interplay between cytokine-mediated inflammatory and laminar flow-mediated anti-inflammatory signaling in endothelial cells. The emphasis will be the regulatory mechanism between JNK and ERK5 and post-translational modification of ERK5 by SUMOylation. We believe that the clarification of these mechanosignaling pathways will lead us to understand the process of atherosclerosis formation in areas exposed to disturbed flow, especially in its initial phase of chronic inflammation.