Flow-Mediated Signaling Modulates Endothelial Cell Phenotype

The focal development of atherosclerosis in the vascular tree may be explained in part by the local nature of blood flow. Bifurcations and branching points, prone to early atherogenesis, experience disturbed and oscillatory flow, whereas straight vascular regions, resistant to atherosclerosis, are exposed to steady laminar flow. A large number of studies suggest that the antiatherosclerotic effects of laminar flow are in part due to the ability of flow to modulate endothelial cell phenotype. Under steady laminar flow, endothelial cells generate molecules that promote a vasoactive, anticoagulant, anti-inflammatory, and growth-inhibitory surface. In contrast, disturbed flow induces a proliferative, prothrombotic, and adhesive phenotype. Endothelial cells are able to sense the variations of flow via mechanosensitive cell surface proteins and to transduce these signals via intracellular pathways to transcription factors in the nucleus leading to phenotypic changes. This review summarizes the "outside-in" signaling events initiated by flow that modulate endothelial cell phenotype.