Role of epithelial Na+ channels in endothelial function

Abstract

An increasing number of mechano-sensitive ion channels in endothelial cells have been identified in response to blood flow and hydrostatic pressure. However, how these channels respond to flow under different physiological and pathological conditions remains unknown. Our results show that epithelial Na+ channels (ENaCs) colocalize with hemeoxygenase-1 (HO-1) and hemeoxygenase-2 (HO-2) within the caveolae on the apical membrane of endothelial cells and are sensitive to stretch pressure and shear stress. ENaCs exhibited low levels of activity until their physiological environment was changed; in this case, the upregulation of HO-1, which in turn facilitated heme degradation and hence increased the carbon monoxide (CO) generation. CO potently increased the bioactivity of ENaCs, releasing the channel from inhibition. Endothelial cells responded to shear stress by increasing the Na+ influx rate. Elevation of intracellular Na+ concentration hampered the transportation of l-arginine, resulting in impaired nitric oxide (NO) generation. Our data suggest that ENaCs that are endogenous to human endothelial cells are mechano-sensitive. Persistent activation of ENaCs could inevitably lead to endothelium dysfunction and even vascular diseases such as atherosclerosis.

Publication DOI: https://doi.org/10.1242/jcs.168831
Divisions: College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
Additional Information: © 2016. Published by The Company of Biologists Ltd. Non-commercial use only
Uncontrolled Keywords: ENaC,endothelium dysfunction,heme,mechanical stress,NO,Cell Biology
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://jcs.bio ... 90.article-info (Publisher URL)
PURE Output Type: Article
Published Date: 2016-01-01
Published Online Date: 2015-11-30
Accepted Date: 2015-11-21
Authors: Guo, Dongqing
Liang, Shenghui
Wang, Su
Tang, Chengchun
Yao, Bin
Wan, Wenhui
Zhang, Hailing
Jiang, Hui
Ahmed, Asif (ORCID Profile 0000-0002-8755-8546)
Zhang, Zhiren
Gu, Yuchun (ORCID Profile 0000-0002-7558-0447)

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