Flow-Mediated Signaling Modulates Endothelial Cell Phenotype

Abstract

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.

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“…Of these, shear stress, which is generated by frictional force, has attracted particular attention. Endothelial cells can sense blood flow via mechanoreceptors and transduce these signals to the nucleus, to cause transcriptional and phenotypic changes (Garin and Berk, 2006). Nitric oxide (NO) signaling plays an important role in Vegf-induced angiogenesis (Ziche et al, 1997).…”

Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

“…The biomechanical environment influences endothelial cell function and regulates key functions of blood vessels including vascular permeability and dilation (18,24,44). Mechanical forces are considered to be the triggers that induce a growth response in the overloaded myocardium (22,50).…”

Flow beats inflammation, but not always

“…The latter have been shown to influence granulocyte/monocyte cell development. 2 markers (CD25, CD69), and decreased cytokine production (eg, IL-2).…”

“…I t has been known for some time that being exposed to laminar shear stress is good when you are a vascular endothelial cell. 1,2 It keeps you calm and quiescent and overall relaxed. There seem to be several possible mechano-transduction mechanisms 3 mediating flow-activated effects, including up-regulation of Krupple-like factor 2 4 (KLF2).…”