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Review
. 2014 Jun;37(6):435-40.
doi: 10.14348/molcells.2014.0078. Epub 2014 Apr 30.

Shear stress and atherosclerosis

Kyung-Sun Heo  1 , Keigi Fujiwara, Jun-ichi Abe
Affiliations
Review

Shear stress and atherosclerosis

Kyung-Sun Heo et al. Mol Cells. 2014 Jun.

Abstract

Hemodynamic shear stress, the frictional force acting on vascular endothelial cells, is crucial for endothelial homeostasis under normal physiological conditions. When discussing blood flow effects on various forms of endothelial (dys)function, one considers two flow patterns: steady laminar flow and disturbed flow because endothelial cells respond differently to these flow types both in vivo and in vitro. Laminar flow which exerts steady laminar shear stress is atheroprotective while disturbed flow creates an atheroprone environment. Emerging evidence has provided new insights into the cellular mechanisms of flow-dependent regulation of vascular function that leads to cardiovascular events such as atherosclerosis, atherothrombosis, and myocardial infarction. In order to study effects of shear stress and different types of flow, various models have been used. In this review, we will summarize our current views on how disturbed flow-mediated signaling pathways are involved in the development of atherosclerosis.

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Figures

Fig. 1.
Fig. 1.
En Face immunohistochemistry. The greater curvature of the aortic arch indicated by the blue circle is exposed to steady laminar flow and is protected from atherosclerosis. Regions of curvature indicated by the red circle and side branches indicated by numbers (1, 2, and 3) are exposed to disturbed flow and are athero-prone areas. The aorta was prepared from a 7 weeks old C57BL/6 wild type mouse. En face endothelial cells stained by anti-VE-cadherin show the general cell morphology in the steady laminar flow (blue square) and disturbed flow (red square) areas. Scale bars, 20 μm.
Fig. 2.
Fig. 2.
Disturbed flow induces EC dysfunction via p53 and ERK5 SUMOylation. Disturbed flow down-regulates SENP2 activity, which then cause EC apoptosis via p53 SUMOylation and subsequent p53-Bcl2 binding. On the other hand, steady laminar flow, through activation of ERK5, increases activity of MEF2/KLF2/eNOS, which are responsible for inducting anti-inflammatory responses. Disturbed flow-induced down-regulation of SENP2 triggers ERK5 SUMOylation and inhibits its transcriptional activity. S-flow, steady laminar flow; D-flow, disturbed flow; SUMO, small ubiquitin-like modifier.
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