期刊
CARDIOVASCULAR RESEARCH
卷 97, 期 3, 页码 562-570出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvs362
关键词
Hypertension; Small arteries; Vascular protection; PPAR gamma; Angiotensin II
资金
- Canadian Institutes of Health Research (CIHR) [37917, 82790]
- Canada Research Chair (CRC) on Hypertension and Vascular Research by the CRC Government of Canada/CIHR Program
- Canada Fund for Innovation (CFI)
- Pfizer Canada
Vascular peroxisome proliferator-activated receptor (PPAR) activation improves vascular remodelling and endothelial function in hypertensive rodents. The goal of this study was to determine that vascular smooth muscle cell (VSMC) PPAR exerts a vascular protective role beyond its metabolic effects. We generated a model of adult inducible VSMC-specific Ppar inactivation to test the hypothesis that PPAR counteracts angiotensin (Ang) II-induced vascular remodelling and endothelial dysfunction. Inducible VSMC Ppar knockout mice were generated by crossing Ppar floxed mice with mice expressing a tamoxifen-inducible Cre recombinase Smooth muscle (Sm) myosin heavy chain promoter control. Eight-to-ten-week-old SmPpar(/) 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 SmPpar(/) mice. Endothelium-dependent relaxation to acetylcholine was reduced in SmPpar(/) mice and further impaired by Ang II infusion, and was unaffected by an inhibitor of NO synthase, suggesting a defect of NO-mediated relaxation. SmPpar deletion increased the sensitivity to Ang II-induced contraction. SmPpar(/) 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 SmPpar deletion. Ang II infusion increased the expression of CD3 T-cell co-receptor chain and decreased Adiponectin in perivascular adipose tissue of SmPpar(/) mice. Inducible Ppar 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 PPAR in angiotensin II-induced vascular injury.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据