Angiotensin II modulates CD40 expression in vascular smooth muscle cells

Autor(es)

Souza, Heraldo P. ^[1] ; Frediani, Denise ^[1] ; Cobra, Ana L. ^[2] ; Moretti, Ana I. ^[1] ; Jurado, Marcia C. ^[1] ; Fernandes, Thadeu R. ^[1] ; Cardounel, Arturo J. ^[3] ; Zweier, Jay L. ^[3] ; Tostes, Rita C. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Emergency Med, BR-02146901 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo - Brazil

^[3] Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 - USA

• Tipo de documento: Artigo Científico
• Fonte: Clinical Science; v. 116, n. 5-6, p. 423-431, MAR 2009.
• Citações Web of Science: 13

Resumo

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. (AU)

• Processo FAPESP: 02/02930-0 - A via de sinalizacao cd40/cd40l na aterosclerose: controle da sua atividade por especies reativas de oxigenio e modificacao de mecanismos aterogenicos atraves do seu bloqueio.
• Beneficiário: Heraldo Possolo de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular