Vascular Endothelium, Biomechanical Forces, and the Pathogenesis of Atherosclerosis

The localization of atherosclerotic lesions to regions of disturbed blood flow associated with certain arterial geometries, in humans and experimental animals, suggests an important role for hemodynamic forces in the pathobiology of atherosclerosis. There is increasing evidence that the vascular endothelium, which is directly exposed to various fluid mechanical stimuli generated by pulsatile blood flow, can discriminate among these different biomechanical stimuli and transduce them into genetic regulatory programs that modulate endothelial function in health and disease. In this seminar, we will discuss how biomechanical stimuli generated by blood flow can influence endothelial functional phenotypes, and explore the working concept of "atheroprone" hemodynamic environments as "local risk factors" in atherogenesis. In addition, we will consider the therapeutic implications of the activation of "atheroprotective genes" and their role(s) as "critical regulatory nodes" in vascular hemostasis.