Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction

Research output: Contribution to journalReview article

56 Citations (Scopus)

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 between flow patterns and activation of reactive oxygen species generating enzymes.

Original languageEnglish (US)
Pages (from-to)2722-2730
Number of pages9
JournalCirculation Journal
Volume75
Issue number12
DOIs
StatePublished - Dec 5 2011

Fingerprint

Protein Kinase C
Blood Vessels
Reactive Oxygen Species
Endothelial Cells
Sumoylation
Vascular Endothelium
Down-Regulation
Tumor Necrosis Factor-alpha
Apoptosis
Inflammation
Enzymes

Keywords

  • Atherosclerosis
  • Blood flow
  • Endothelial dysfunction
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. / Heo, Kyung Sun; Fujiwara, Keigi; Abe, Jun Ichi.

In: Circulation Journal, Vol. 75, No. 12, 05.12.2011, p. 2722-2730.

Research output: Contribution to journalReview article

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