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Cholesterol Enrichment Impairs Capacitative Calcium Entry, eNOS Phosphorylation & Shear Stress-Induced NO Production
Journal article   Open access   Peer reviewed

Cholesterol Enrichment Impairs Capacitative Calcium Entry, eNOS Phosphorylation & Shear Stress-Induced NO Production

Allison M. Andrews, Tenderano T. Muzorewa, Kelly A. Zaccheo, Donald G. Buerk, Dov Jaron and Kenneth A. Barbee
Cellular and molecular bioengineering, v 10(1)
06 Jul 2016
DOI: https://doi.org/10.1007/s12195-016-0456-5
PMID: 28138348
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1007/s12195-016-0456-5View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Atherosclerosis Capacitative calcium entry Cholesterol Endothelial cells Nitric oxide Shear stress
Endothelial dysfunction, characterized by decreased production or availability of nitric oxide (NO), is widely believed to be the hallmark of early-stage atherosclerosis. In addition, hypercholesterolemia is considered a major risk factor for development of atherosclerosis and is associated with impaired flow-induced dilation. However, the mechanism by which elevated cholesterol levels leads to decreased production of NO is unclear. NO is released in response to shear stress and agonist-evoked changes in intracellular calcium. Although calcium signaling is complex, we have previously shown that NO production by endothelial nitric oxide synthase (eNOS) is preferentially activated by calcium influx via store-operated channels. We hypothesized that cholesterol enrichment altered this signaling pathway (known as capacitive calcium entry; CCE) ultimately leading to decreased NO. Our results show that cholesterol enrichment abolished ATP-induced eNOS phosphorylation and attenuated the calcium response by the preferential inhibition of CCE. Furthermore, cholesterol enrichment also inhibited shear stress-induced NO production and eNOS phosporylation, consistent with our previous results showing a significant role for ATP autocrine stimulation and subsequent activation of CCE in the endothelial flow response.

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11 Record Views
11 citations in Web of Science
10 citations in Scopus

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UN Sustainable Development Goals (SDGs)

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Collaboration types
Domestic collaboration
Web of Science research areas
Biophysics
Cell & Tissue Engineering
Cell Biology
Engineering, Biomedical
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