Angiotensin II modulates CD40 expression in vascular smooth muscle cells

  • Souza H
  • Frediani D
  • Cobra A
 et al. 
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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)-1
beta or TNF-alpha (tumour necrosis factor-a) 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 P22(phox) 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.

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Authors

  • Heraldo P Souza

  • Denise Frediani

  • Ana L Cobra

  • Ana I Moretti

  • Marcia C Jurado

  • Thadeu R Fernandes

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