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

Fingerprint

CD40 Ligand
Vascular Smooth Muscle
Angiotensin II
Smooth Muscle Myocytes
Blood Vessels
Reactive Oxygen Species
Atherosclerosis
Coronary Vessels
Antioxidants
Electron Spin Resonance Spectroscopy
Atherosclerotic Plaques
Prostaglandin-Endoperoxide Synthases
Interleukin-8
Interleukin-1
Immunoblotting
Superoxides
Transfection
Rupture
Oxidative Stress
Cell Culture Techniques

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Souza, H. P., Frediani, D., Cobra, A. L., Moretti, A. I., Jurado, M. C., Fernandes, T. R., ... 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

Angiotensin II modulates CD40 expression in vascular smooth muscle cells. / Souza, Heraldo P.; Frediani, Denise; Cobra, Ana L.; Moretti, Ana I.; Jurado, Márcia C.; Fernandes, Thadeu R.; Cardounel, Arturo J.; Zweier, Jay L.; Tostes, Rita C.

In: Clinical Science, Vol. 116, No. 5, 03.2009, p. 423-431.

Research output: Contribution to journalArticle

Souza, HP, Frediani, D, Cobra, AL, Moretti, AI, Jurado, MC, Fernandes, TR, Cardounel, AJ, Zweier, JL & Tostes, RC 2009, 'Angiotensin II modulates CD40 expression in vascular smooth muscle cells', Clinical Science, vol. 116, no. 5, pp. 423-431. https://doi.org/10.1042/CS20080155
Souza HP, Frediani D, Cobra AL, Moretti AI, Jurado MC, Fernandes TR et al. Angiotensin II modulates CD40 expression in vascular smooth muscle cells. Clinical Science. 2009 Mar;116(5):423-431. https://doi.org/10.1042/CS20080155
Souza, Heraldo P. ; Frediani, Denise ; Cobra, Ana L. ; Moretti, Ana I. ; Jurado, Márcia C. ; Fernandes, Thadeu R. ; Cardounel, Arturo J. ; Zweier, Jay L. ; Tostes, Rita C. / Angiotensin II modulates CD40 expression in vascular smooth muscle cells. In: Clinical Science. 2009 ; Vol. 116, No. 5. pp. 423-431.
@article{9f464fb339124f35b2e0b7dee5d77aa9,
title = "Angiotensin II modulates CD40 expression in vascular smooth muscle cells",
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.",
keywords = "Atherosclerosis, CD40, Cytokine, Electron paramagnetic resonance, Hypertension, Superoxide",
author = "Souza, {Heraldo P.} and Denise Frediani and Cobra, {Ana L.} and Moretti, {Ana I.} and Jurado, {M{\'a}rcia C.} and Fernandes, {Thadeu R.} and Cardounel, {Arturo J.} and Zweier, {Jay L.} and Tostes, {Rita C.}",
year = "2009",
month = "3",
doi = "10.1042/CS20080155",
language = "English (US)",
volume = "116",
pages = "423--431",
journal = "Clinical Science",
issn = "0143-5221",
publisher = "Portland Press Ltd.",
number = "5",

}

TY - JOUR

T1 - Angiotensin II modulates CD40 expression in vascular smooth muscle cells

AU - Souza, Heraldo P.

AU - Frediani, Denise

AU - Cobra, Ana L.

AU - Moretti, Ana I.

AU - Jurado, Márcia C.

AU - Fernandes, Thadeu R.

AU - Cardounel, Arturo J.

AU - Zweier, Jay L.

AU - Tostes, Rita C.

PY - 2009/3

Y1 - 2009/3

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - CD40

KW - Cytokine

KW - Electron paramagnetic resonance

KW - Hypertension

KW - Superoxide

UR - http://www.scopus.com/inward/record.url?scp=63449130747&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63449130747&partnerID=8YFLogxK

U2 - 10.1042/CS20080155

DO - 10.1042/CS20080155

M3 - Article

C2 - 18785879

AN - SCOPUS:63449130747

VL - 116

SP - 423

EP - 431

JO - Clinical Science

JF - Clinical Science

SN - 0143-5221

IS - 5

ER -