Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
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Disturbed-Flow-Mediated Vascular Reactive Oxygen Species Induce Endothelial Dysfunction
Kyung-Sun HeoKeigi FujiwaraJun-ichi Abe
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2011 Volume 75 Issue 12 Pages 2722-2730

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Abstract

Emerging evidence is revealing the different roles of steady laminar flow (s-flow) and disturbed flow (d-flow) in the regulation of the vascular endothelium. s-flow is atheroprotective while d-flow creates an atheroprone environment. Most recently, we found unique atheroprone signals, which involve protein kinase C (PKC)ζ activation, elicited by d-flow. We and others have defined a novel role for PKCζ as a shared mediator for tumor necrosis factor alpha (TNF alpha) and d-flow, which cause pro-inflammatory and pro-apoptotic events in endothelial cells (ECs) in the atheroprone environment. Under such conditions, ONOO- formation is increased in a d-flow-mediated PKCζ-dependent manner. Here, we propose a new signaling pathway involving d-flow-induced EC inflammation via PKCζ-ERK5 interaction-mediated downregulation of KLF2/eNOS stability, which leads to PKCζ-mediated p53-SUMOylation and EC apoptosis. In addition, we highlight several mechanisms contributing to endothelial dysfunction, focusing on the relations bet-ween flow patterns and activation of reactive oxygen species generating enzymes. (Circ J 2011; 75: 2722-2730)

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© 2011 THE JAPANESE CIRCULATION SOCIETY
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