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学科主题: 基础医学
题名:
PPAR delta Activation Protects Endothelial Function in Diabetic Mice
作者: Tian, Xiao Yu1; Wong, Wing Tak1,2; Wang, Nanping3,4; Lu, Ye1; Cheang, Wai San1; Liu, Jian1; Liu, Limei1,5; Liu, Yahan4; Lee, Susanna Sau-Tuen6; Chen, Zhen Yu6; Cooke, John P.2; Yao, Xiaoqiang1; Huang, Yu1
刊名: DIABETES
发表日期: 2012-12-01
DOI: 10.2337/db12-0117
卷: 61, 期:12, 页:3285-3293
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Endocrinology & Metabolism
研究领域[WOS]: Endocrinology & Metabolism
关键词[WOS]: INFLAMMATORY ADHESION MOLECULES ; RECEPTOR-DELTA ; SIGNALING PATHWAY ; OXIDATIVE STRESS ; PROGENITOR CELLS ; INSULIN SENSITIVITY ; LIPID-PEROXIDATION ; ACID OXIDATION ; UP-REGULATION ; GAMMA
英文摘要:

Recent evidence highlights the therapeutic potential of peroxisome proliferator-activated receptor-delta (PPAR delta) agonists to increase insulin sensitivity hi diabetes. However, the role of PPAR delta in regulating vascular function is incompletely characterized. We investigate whether PPAR delta activation improves endothelial function in diabetic and obese mice. PPAR delta knockout (KO) and wild-type (WT) mice fed with high-fat diet and db/db mice were used as diabetic mouse models, compared with PPAR delta KO and WT mice on normal diet and db/m(+) mice. Endothelium-dependent relaxation (EDR) was measured by wire myograph. Flow-mediated vasodilatation (FMD) was measured by pressure myograph. Nitric oxide (NO) production was examined in primary endothelial cells from mouse aortae. PPAR delta agonist GW1516 restored EDRs in mouse aortae under high-glucose conditions or in db/db mouse aortae ex vivo. After oral treatment with GW1516, EDRs in aortae and FMDs in mesenteric resistance arteries were improved in obese mice in a PPAR delta-specific manner. The effects of GW1516 on endothelial function were mediated through phosphatidylinositol 3-kinase (PI3K) and Ala with a subsequent increase of endothelial nitric oxide synthase (eNOS) activity and NO production. The current study demonstrates an endothelial-protective effect of PPAR delta agonists in diabetic mice through PI3K/Akt/eNOS signaling, suggesting the therapeutic potential of PPAR delta agonists for diabetic vasculopathy. Diabetes 61:3285-3293, 2012

语种: 英语
所属项目编号: N_CUHK428/09 ; 30890041 ; 30931160434 ; 2010CB912502 ; 2012CB517805 ; 2140676 ; 465611
项目资助者: Natural Science Foundation of China/Research Grants Council of Hong Kong Joint Research Scheme ; National Science Foundation of China ; Ministry of Science and Technology of China (973 programs) ; Hong Kong General Research Fund
WOS记录号: WOS:000312041700036
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52789
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Chinese Univ Hong Kong, Inst Vasc Med, Li Ka Shing Inst Hlth Sci, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China
2.Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA
3.Xi An Jiao Tong Univ, Cardiovasc Res Ctr, Xian 710049, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100871, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China
6.Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China

Recommended Citation:
Tian, Xiao Yu,Wong, Wing Tak,Wang, Nanping,et al. PPAR delta Activation Protects Endothelial Function in Diabetic Mice[J]. DIABETES,2012,61(12):3285-3293.
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