The signalling pathway CD40/CD40L (CD40 ligand) plays an important role in atherosclerotic plaque formation and rupture. AngII (angiotensin II), which induces oxidative stress and inflammation, is also implicated in the progression of atherosclerosis. In the present study, we tested the hypothesis that AngII increases CD40/CD40L activity in vascular cells and that ROS (reactive oxygen species) are part of the signalling cascade that controls CD40/CD40L expression. Human CASMCs (coronary artery smooth muscle cells) in culture exposed to IL (interleukin)-1β or TNF-α (tumour necrosis factor-α) had increased superoxide generation and enhanced CD40 expression, detected by EPR (electron paramagnetic resonance) and immunoblotting respectively. Both phenomena were abolished by previous incubation with membrane-permeant antioxidants or cell transfection with p22phoxantisense. AngII (50–200 nmol/l) induced an early and sustained increase in CD40 mRNA and protein expression in CASMCs, which was blocked by treatment with antioxidants. Increased CD40 expression led to enhanced activity of the pathway, as AngII-treated cells stimulated with recombinant CD40L released higher amounts of IL-8 and had increased COX-2 (cyclo-oxygenase-2) expression. We conclude that AngII stimulation of vascular cells leads to a ROS-dependent increase in CD40/CD40L signalling pathway activity. This phenomenon may be an important mechanism modulating the arterial injury observed in atherosclerosis-related vasculopathy.
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March 2009
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Research Article|
February 02 2009
Angiotensin II modulates CD40 expression in vascular smooth muscle cells
Heraldo P. Souza;
*Department of Emergency Medicine, School of Medicine, University of Sao Paulo, 01246-9013 Sao Paulo, Brazil
Correspondence: Dr Heraldo P. Souza (email [email protected]).
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Denise Frediani;
Denise Frediani
*Department of Emergency Medicine, School of Medicine, University of Sao Paulo, 01246-9013 Sao Paulo, Brazil
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Ana L. Cobra;
Ana L. Cobra
†Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-900 Sao Paulo, Brazil
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Ana I. Moretti;
Ana I. Moretti
*Department of Emergency Medicine, School of Medicine, University of Sao Paulo, 01246-9013 Sao Paulo, Brazil
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Márcia C. Jurado;
Márcia C. Jurado
*Department of Emergency Medicine, School of Medicine, University of Sao Paulo, 01246-9013 Sao Paulo, Brazil
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Thadeu R. Fernandes;
Thadeu R. Fernandes
*Department of Emergency Medicine, School of Medicine, University of Sao Paulo, 01246-9013 Sao Paulo, Brazil
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Arturo J. Cardounel;
Arturo J. Cardounel
‡Davis Heart & Lung Research Institute, Ohio State University, Columbus, OH 43210, U.S.A.
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Jay L. Zweier;
Jay L. Zweier
‡Davis Heart & Lung Research Institute, Ohio State University, Columbus, OH 43210, U.S.A.
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Rita C. Tostes
Rita C. Tostes
†Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-900 Sao Paulo, Brazil
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Publisher: Portland Press Ltd
Received:
May 14 2008
Revision Received:
July 17 2008
Accepted:
September 11 2008
Accepted Manuscript online:
September 11 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2009 Biochemical Society
2009
Clin Sci (Lond) (2009) 116 (5): 423–431.
Article history
Received:
May 14 2008
Revision Received:
July 17 2008
Accepted:
September 11 2008
Accepted Manuscript online:
September 11 2008
Citation
Heraldo P. Souza, Denise Frediani, Ana L. Cobra, Ana I. Moretti, Márcia C. Jurado, Thadeu R. Fernandes, Arturo J. Cardounel, Jay L. Zweier, Rita C. Tostes; Angiotensin II modulates CD40 expression in vascular smooth muscle cells. Clin Sci (Lond) 1 March 2009; 116 (5): 423–431. doi: https://doi.org/10.1042/CS20080155
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