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

TitlePivotal role of protein kinase Cδ in angiotensin II-induced endothelial cyclooxygenase-2 expression: A link to vascular inflammation
Authors
Keywordsangiotensin II
cyclooxygenase-2
endothelium
monocyte chemoattractant protein-1
protein kinase Cδ
Issue Date2011
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.lww.com/product/?1079-5642
Citation
Arteriosclerosis, Thrombosis, And Vascular Biology, 2011, v. 31 n. 5, p. 1169-1176 How to Cite?
AbstractObjective- 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. Copyright © 2011 American Heart Association. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/139453
ISSN
2015 Impact Factor: 5.969
2015 SCImago Journal Rankings: 3.356
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilCUHK465308M
CUHK466110
HKU2/07C
HKU4/CRF10
Deutsche Forschungsgemeinschaft
Chinese University of Hong Kong
Funding Information:

This study was supported by the Hong Kong Research Grant Council (Grants CUHK465308M, CUHK466110, HKU2/07C, and HKU4/CRF10), Deutsche Forschungsgemeinschaft, Germany-Hong Kong Joint Research Scheme, and Focused Investment Scheme of Chinese University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorWong, SLen_HK
dc.contributor.authorLau, CWen_HK
dc.contributor.authorWong, WTen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorAu, CLen_HK
dc.contributor.authorNg, CFen_HK
dc.contributor.authorNg, SSMen_HK
dc.contributor.authorGollasch, Men_HK
dc.contributor.authorYao, Xen_HK
dc.contributor.authorHuang, Yen_HK
dc.date.accessioned2011-09-23T05:50:14Z-
dc.date.available2011-09-23T05:50:14Z-
dc.date.issued2011en_HK
dc.identifier.citationArteriosclerosis, Thrombosis, And Vascular Biology, 2011, v. 31 n. 5, p. 1169-1176en_HK
dc.identifier.issn1079-5642en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139453-
dc.description.abstractObjective- 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. Copyright © 2011 American Heart Association. All rights reserved.en_HK
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.lww.com/product/?1079-5642en_HK
dc.relation.ispartofArteriosclerosis, Thrombosis, and Vascular Biologyen_HK
dc.subjectangiotensin IIen_HK
dc.subjectcyclooxygenase-2en_HK
dc.subjectendotheliumen_HK
dc.subjectmonocyte chemoattractant protein-1en_HK
dc.subjectprotein kinase Cδen_HK
dc.subject.meshAngiotensin II - administration and dosage - metabolism-
dc.subject.meshAtherosclerosis - enzymology-
dc.subject.meshCyclooxygenase 2 - metabolism-
dc.subject.meshEndothelial Cells - drug effects - enzymology-
dc.subject.meshInflammation - enzymology-
dc.titlePivotal role of protein kinase Cδ in angiotensin II-induced endothelial cyclooxygenase-2 expression: A link to vascular inflammationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1524-4636 (Electronic) 1079-5642 (Linkin&volume=31&issue=5&spage=1169&epage=76&date=2011&atitle=Pivotal+role+of+protein+kinase+Cdelta+in+angiotensin+II-induced+endothelial+cyclooxygenase-2+expression:+a+link+to+vascular+inflammationen_US
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1161/ATVBAHA.110.216044en_HK
dc.identifier.pmid21311042-
dc.identifier.scopuseid_2-s2.0-79955613595en_HK
dc.identifier.hkuros194039en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955613595&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume31en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1169en_HK
dc.identifier.epage1176en_HK
dc.identifier.eissn1524-4636-
dc.identifier.isiWOS:000289720800033-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWong, SL=26634414200en_HK
dc.identifier.scopusauthoridLau, CW=7401968520en_HK
dc.identifier.scopusauthoridWong, WT=35932584500en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridAu, CL=7102805672en_HK
dc.identifier.scopusauthoridNg, CF=8519137200en_HK
dc.identifier.scopusauthoridNg, SSM=47661276100en_HK
dc.identifier.scopusauthoridGollasch, M=7003908655en_HK
dc.identifier.scopusauthoridYao, X=7402529434en_HK
dc.identifier.scopusauthoridHuang, Y=34770945300en_HK

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