Pivotal role of protein kinase Cδ in angiotensin II-induced endothelial cyclooxygenase-2 expression: A link to vascular inflammation

Siu Ling Wong, Chi Wai Lau, Wing Tak Wong, Aimin Xu, Chak Leung Au, Chi Fai Ng, Simon Siu Man Ng, Maik Gollasch, Xiaoqiang Yao, Yu Huang

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Objective- The purpose of this study was to examine the hypothesis that angiotensin II (Ang II) induced endothelial cyclooxygenase-2 (COX-2) expression, which in turn mediated the generation of proinflammatory cytokines. Methods and Results- Western blot analysis on primary rat endothelial cells showed Ang II induced COX-2 expression, which was abolished by cotreatment of p38 mitogen-activated protein kinase (SB 202190) and extracellular signal-regulated kinase 1/2 (PD 98059) inhibitors. Protein kinase Cδ (PKCδ) inhibitor (rottlerin) prevented extracellular signal-regulated kinase 1/2 phosphorylation and COX-2 expression. The pivotal role of PKCδ was further supported by a similar stimulatory effect of the PKC activator on COX-2 expression, signified by Ang II-stimulated translocation of PKCδ to the plasma membrane, and confirmed by PKCδ phosphorylation at Tyr311. Small interfering RNA targeting PKCδ diminished COX-2 expression, which was further abrogated by SB 202190. Human mesenteric arteries incubated with Ang II showed increased levels of endothelial COX-2 and monocyte chemoattractant protein-1; the former was inhibited by SB 202190 plus rottlerin, whereas the latter was prevented by COX-2 inhibitor. Conclusion- The present study pinpoints a novel role of PKCδ in Ang II-induced endothelial COX-2 upregulation and identifies a COX-2-dependent proatherosclerotic cytokine monocyte chemoattractant protein-1. The findings raise the possibility of curtailing endothelial COX-2 expression as a means of limiting or preventing vascular inflammation.

Original languageEnglish (US)
Pages (from-to)1169-1176
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • angiotensin II
  • cyclooxygenase-2
  • endothelium
  • monocyte chemoattractant protein-1
  • protein kinase Cδ

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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