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Protective role of vascular smooth muscle cell PPARγ in angiotensin II-induced vascular disease.
Marchesi, Chiara; Rehman, Asia; Rautureau, Yohann; Kasal, Daniel A; Briet, Marie; Leibowitz, Avshalom; Simeone, Stefania M C; Ebrahimian, Talin; Neves, Mario F; Offermanns, Stefan; Gonzalez, Frank J; Paradis, Pierre; Schiffrin, Ernesto L.
Afiliação
  • Marchesi C; Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Cardiovasc Res ; 97(3): 562-70, 2013 Mar 01.
Article em En | MEDLINE | ID: mdl-23250918
AIMS: Vascular peroxisome proliferator-activated receptor γ (PPARγ) activation improves vascular remodelling and endothelial function in hypertensive rodents. The goal of this study was to determine that vascular smooth muscle cell (VSMC) PPARγ exerts a vascular protective role beyond its metabolic effects. METHODS AND RESULTS: We generated a model of adult inducible VSMC-specific Pparγ inactivation to test the hypothesis that PPARγ counteracts angiotensin (Ang) II-induced vascular remodelling and endothelial dysfunction. Inducible VSMC Pparγ knockout mice were generated by crossing Pparγ floxed mice with mice expressing a tamoxifen-inducible Cre recombinase Smooth muscle (Sm) myosin heavy chain promoter control. Eight-to-ten-week-old SmPparγ(-/-) and control mice were infused with a nonpressor dose of Ang II for 7 days. Blood pressure was unaffected. Mesenteric arteries showed eutrophic remodelling in Ang II-infused control mice and hypertrophic remodelling in Ang II-infused SmPparγ(-/-) mice. Endothelium-dependent relaxation to acetylcholine was reduced in SmPparγ(-/-) mice and further impaired by Ang II infusion, and was unaffected by an inhibitor of NO synthase, suggesting a defect of NO-mediated relaxation. SmPparγ deletion increased the sensitivity to Ang II-induced contraction. SmPparγ(-/-) mice exhibited enhanced Ang II-induced vascular NADPH oxidase activity and adhesion molecule ICAM-1 and chemokine monocyte chemotactic protein-1 expression. The antioxidant Superoxide dismutase 3 expression was decreased by SmPparγ deletion. Ang II infusion increased the expression of CD3 T-cell co-receptor chain δ and decreased Adiponectin in perivascular adipose tissue of SmPparγ(-/-) mice. CONCLUSION: Inducible Pparγ inactivation in VSMCs exacerbated Ang II-induced vascular remodelling and endothelial dysfunction via enhanced vascular oxidative stress and inflammation, revealing the protective role of VSMC PPARγ in angiotensin II-induced vascular injury.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Vasculares / Angiotensina II / PPAR gama / Músculo Liso Vascular Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cardiovasc Res Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Vasculares / Angiotensina II / PPAR gama / Músculo Liso Vascular Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cardiovasc Res Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Canadá