This review highlights how local haemodynamic forces and shear stress dictate endothelial cell phenotype, explaining the focal nature of atherosclerotic plaque development at arterial branches.
Haemodynamic forces influence the functional properties of vascular endothelium. Endothelial cells (ECs) have a variety of receptors, which sense flow and transmit mechanical signals through mechanosensitive signalling pathways to recipient molecules that lead to phenotypic and functional changes. Arterial architecture varies greatly exhibiting bifurcations, branch points and curved regions, which are exposed to various flow patterns. Clinical studies showed that atherosclerotic plaques develop preferentially at arterial branches and curvatures, that is in the regions exposed to disturbed flow and shear stress. In the atheroprone regions, the endothelium has a proinflammatory phenotype associated with low nitric oxide production, reduced barrier function and increased proadhesive, procoagulant and proproliferative properties. Atheroresistant regions are exposed to laminar flow and high shear stress that induce prosurvival antioxidant signals and maintain the quiescent phenotype in ECs. Indeed, various flow patterns contribute to phenotypic and functional heterogeneity of arterial endothelium whose response to proatherogenic stimuli is differentiated. This may explain the preferential development of endothelial dysfunction in arterial sites with disturbed flow.
Chistiakov et al. (2016) studied this question.