DIFFERENTIAL GENE EXPRESSION OF ENDOTHELIAL CELLS UNDER HIGH WALL SHEAR STRESS AND SPATIAL GRADIENTS

摘要

In both human and animal models, cerebral aneurysms tend to develop at the apices of bifurcations in the cerebral vasculature. Due to the focal nature of aneurysm development it has long been speculated that hemodynamics are an important factor in aneurysm susceptibility. The local hemodynamics of bifurcations are complex, being characterized by flow impingement causing a high frictional force on the vessel wall known as wall shear stress (WSS) and significant flow acceleration or deceleration, manifested as the positive or negative spatial gradient of WSS (WSSG). In vivo studies have recently identified that aneurysm initiation occurs at areas of the vessel wall that experience a combination of both high WSS and positive WSSG [1,2]rnAs the inner most lining of the blood vessel wall, endothelial cells (ECs) are uniquely situated to act as the signal transduction interface between the WSS generated by flowing blood and the underlying tissue. WSS can modulate EC morphology, ion channel activation, and gene expression [3]. Under baseline WSS conditions (15-25 dyn/cm2) ECs enter a quiescent, anti-thrombotic and anti-inflammatory state [4]. However, very little is known about the effect of the high WSS and spatial WSSGs that are implicated in the initiation of cerebral aneurysms. This study identifies the comprehensive gene expression profiles of ECs subjected to high WSS and spatial WSSGs using eDNA microarrays.