Angiotensin II modulates CD40 expression in vascular smooth muscle cells

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

Research output: Contribution to journalArticle

Abstract

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 p22phox antisense. 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.

Original languageEnglish (US)
Pages (from-to)423-431
Number of pages9
JournalClinical Science
Volume116
Issue number5
DOIs
StatePublished - Mar 2009
Externally publishedYes

Keywords

  • Atherosclerosis
  • CD40
  • Cytokine
  • Electron paramagnetic resonance
  • Hypertension
  • Superoxide

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Souza, H. P., Frediani, D., Cobra, A. L., Moretti, A. I., Jurado, M. C., Fernandes, T. R., Cardounel, A. J., Zweier, J. L., & Tostes, R. C. (2009). Angiotensin II modulates CD40 expression in vascular smooth muscle cells. Clinical Science, 116(5), 423-431. https://doi.org/10.1042/CS20080155