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Endothelial fluid shear stress sensing in vascular health and disease
Nicolas Baeyens, … , Sanguk Yun, Martin A. Schwartz
Nicolas Baeyens, … , Sanguk Yun, Martin A. Schwartz
Published March 1, 2016
Citation Information: J Clin Invest. 2016;126(3):821-828. https://doi.org/10.1172/JCI83083.
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Review

Endothelial fluid shear stress sensing in vascular health and disease

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Abstract

Endothelial cells transduce the frictional force from blood flow (fluid shear stress) into biochemical signals that regulate gene expression and cell behavior via specialized mechanisms and pathways. These pathways shape the vascular system during development and during postnatal and adult life to optimize flow to tissues. The same pathways also contribute to atherosclerosis and vascular malformations. This Review covers recent advances in basic mechanisms of flow signaling and the involvement of these mechanisms in vascular physiology, remodeling, and these diseases. We propose that flow sensing pathways that govern normal morphogenesis can contribute to disease under pathological conditions or can be altered to induce disease. Viewing atherosclerosis and vascular malformations as instances of pathological morphogenesis provides a unifying perspective that may aid in developing new therapies.

Authors

Nicolas Baeyens, Chirosree Bandyopadhyay, Brian G. Coon, Sanguk Yun, Martin A. Schwartz

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Figure 1

Fluid shear stress sensing in physiological and pathological vascular remodeling.

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Fluid shear stress sensing in physiological and pathological vascular re...
FSS acts on mechanosensors including the junctional mechanosensory complex consisting of PECAM-1, VEGFRs, and VE-cadherin (VE-Cad), with the latter also linked to the CCM complex (CCM1, CCM2, and CCM3). Left: Changes in flow due to growth or exercise that result in sustained deviation from the set point result in changes in the activation state of flow-dependent pathways, which mediate physiological remodeling to restore normal shear stress levels. Center: Mutations in CCM genes results in abnormal flow sensing and pathological remodeling, with subsequent formation of abnormal, low-flow vessels. Right: Regions of disturbed flow, in the presence of systemic risk factors, result in pathological remodeling to form atherosclerotic plaque. β-cat, β-catenin; HEG, heart-of-glass.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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