Vascular endothelial responses to disturbed flow: Pathologic implications for atherosclerosis

Atherosclerosis is prone to develop at branches and bends of the arterial tree, where laminar blood flow is disturbed by recirculation, with a non-uniform and irregular distribution of wall shear stress. Vascular endothelial cells (ECs) form an interface between the flowing blood and the vessel wall, and are exposed to blood flow-induced shear stress. Recent evidence suggests that laminar blood flow and sustained high shear stress modulate the expression of EC genes and proteins that function to protect against atherosclerosis, whereas disturbed flow and the associated oscillatory and low shear stress up-regulate pro-atherosclerotic genes and proteins that promote development of atherosclerosis. Understanding of the effects of disturbed flow on ECs not only provides mechanistic insights into the role of complex flow patterns in the pathogenesis of atherosclerosis, but also helps to define the differences between quiescent (non-atherogenic) and activated (atherogenic) ECs, which may lead to the discovery and identification of new therapeutic strategies. In this chapter, we summarize the current experimental and theoretical knowledge on the effects of disturbed flow on ECs, in terms of their signal transduction, gene expression, structure, and function. Our purpose is to provide the basic information on the effects of disturbed flow on ECs that is necessary to understand the etiology of lesion development in the disturbed flow-regions of the arterial tree.