| First Author | Marchesi C | Year | 2013 |
| Journal | Cardiovasc Res | Volume | 97 |
| Issue | 3 | Pages | 562-70 |
| PubMed ID | 23250918 | Mgi Jnum | J:210280 |
| Mgi Id | MGI:5569894 | Doi | 10.1093/cvr/cvs362 |
| Citation | Marchesi C, et al. (2013) Protective role of vascular smooth muscle cell PPARgamma in angiotensin II-induced vascular disease. Cardiovasc Res 97(3):562-70 |
| abstractText | AIMS: Vascular peroxisome proliferator-activated receptor gamma (PPARgamma) activation improves vascular remodelling and endothelial function in hypertensive rodents. The goal of this study was to determine that vascular smooth muscle cell (VSMC) PPARgamma exerts a vascular protective role beyond its metabolic effects. METHODS AND RESULTS: We generated a model of adult inducible VSMC-specific Ppargamma inactivation to test the hypothesis that PPARgamma counteracts angiotensin (Ang) II-induced vascular remodelling and endothelial dysfunction. Inducible VSMC Ppargamma knockout mice were generated by crossing Ppargamma floxed mice with mice expressing a tamoxifen-inducible Cre recombinase Smooth muscle (Sm) myosin heavy chain promoter control. Eight-to-ten-week-old SmPpargamma(-/-) 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 SmPpargamma(-/-) mice. Endothelium-dependent relaxation to acetylcholine was reduced in SmPpargamma(-/-) mice and further impaired by Ang II infusion, and was unaffected by an inhibitor of NO synthase, suggesting a defect of NO-mediated relaxation. SmPpargamma deletion increased the sensitivity to Ang II-induced contraction. SmPpargamma(-/-) 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 SmPpargamma deletion. Ang II infusion increased the expression of CD3 T-cell co-receptor chain delta and decreased Adiponectin in perivascular adipose tissue of SmPpargamma(-/-) mice. CONCLUSION: Inducible Ppargamma 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 PPARgamma in angiotensin II-induced vascular injury. |
