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Pivotal role of protein kinase C(δ) in angiotensin II-induced endothelial cyclooxygenase-2 expression: a link to vascular inflammation

Item Type:Article
Title:Pivotal role of protein kinase C(δ) in angiotensin II-induced endothelial cyclooxygenase-2 expression: a link to vascular inflammation
Creators Name:Wong, S.L. and Lau, C.W. and Wong, W.T. and Xu, A. and Au, C.L. and Ng, C.F. and Ng, S.S.M. and Gollasch, M. and Yao, X. and Huang, Y.
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 C{delta} (PKC{delta}) inhibitor (rottlerin) prevented extracellular signal-regulated kinase 1/2 phosphorylation and COX-2 expression. The pivotal role of PKC{delta} was further supported by a similar stimulatory effect of the PKC activator on COX-2 expression, signified by Ang II-stimulated translocation of PKC{delta} to the plasma membrane, and confirmed by PKC{delta} phosphorylation at Tyr311. Small interfering RNA targeting PKC{delta} 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. Conclusions: The present study pinpoints a novel role of PKC{delta} 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.
Keywords:Angiotensin II, Endothelium, Cyclooxygenase-2, Monocyte Chemoattractant Protein-1, Protein Kinase C-{Delta}, Animals, Rats
Source:Arteriosclerosis Thrombosis and Vascular Biology
ISSN:1079-5642
Publisher:American Heart Association (U.S.A.)
Volume:31
Number:5
Page Range:1169-1176
Date:May 2011
Official Publication:https://doi.org/10.1161/ATVBAHA.110.216044
PubMed:View item in PubMed

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