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学科主题: 基础医学
题名:
Peroxisome Proliferator-Activated Receptor-gamma Ameliorates Pulmonary Arterial Hypertension by Inhibiting 5-Hydroxytryptamine 2B Receptor
作者: Liu, Yahan1; Tian, Xiao Yu2; Mao, Guangmei1; Fang, Xi1; Fung, Man Lung3; Shyy, John Y. -J.4; Huang, Yu2; Wang, Nanping1,4
关键词: vasoconstriction ; pulmonary arterial hypertension ; 5-hydroxytryptamine 2B receptor ; peroxisome proliferator-activated receptor-gamma
刊名: HYPERTENSION
发表日期: 2012-12-01
DOI: 10.1161/HYPERTENSIONAHA.112.198887
卷: 60, 期:6, 页:1471-U261
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Peripheral Vascular Disease
研究领域[WOS]: Cardiovascular System & Cardiology
关键词[WOS]: ADENOVIRUS-MEDIATED OVEREXPRESSION ; INTERCELLULAR-ADHESION MOLECULE-1 ; PLASMA SEROTONIN LEVELS ; SMOOTH-MUSCLE-CELLS ; THERAPEUTIC TARGETS ; ENDOTHELIAL-CELLS ; C-JUN ; RATS ; ANTAGONIST ; DISEASE
英文摘要:

An elevated plasma level of 5-hydroxytryptamine (5-HT) or upregulation of 5-HT receptor signaling or both is implicated in vascular contraction and remodeling in pulmonary arterial hypertension (PAH). Recently, peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists have been shown to ameliorate PAH. However, their effects on the 5-HT-induced contraction of pulmonary arteries remain unknown. Here, we examined the role of PPAR gamma in inhibiting 5-HT2B receptor (5-HT2BR) to ameliorate PAH. Pulmonary arteries from PAH rats induced by monocrotaline or chronic hypoxia showed an enhanced vasoconstriction in response to BW723C86, a specific agonist for 5-HT2BR. Expression of 5-HT2BR was also increased in pulmonary arteries from the PAH rats, accompanied by vascular remodeling and right ventricular hypertrophy. Treatment with the PPAR gamma agonist rosiglitazone in vivo reversed the expression and the vasocontractive effect of 5-HT2BR as well as the thickening of pulmonary arteries. In pulmonary artery smooth muscle cells, 5-HT induced the gene expression of 5-HT2BR, which was inhibited by rosiglitazone, pioglitazone, or adenovirus-mediated overexpression of constitutively activated PPAR gamma. The pharmacological effect of PPAR gamma was through the suppression of the 5-HT-induced activator protein-1 activity. These results demonstrated the beneficial effect of PPAR gamma on 5-HT2BR-mediated vasocontraction, providing a new mechanism for the potential use of PPAR gamma agonists in PAH. (Hypertension. 2012;60:1471-1478.)

语种: 英语
所属项目编号: N_CUHK428/09 ; 30931160434 ; 30890041 ; 2010CB912500 ; CUHK46610
项目资助者: National Natural Science Foundation of China/Research Grants Council ; National Science Foundation of China ; Ministry of Science and Technology of China ; Hong Kong General Research Fund
WOS记录号: WOS:000311105900027
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56092
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.Peking Univ, Inst Cardiovasc Sci, Hlth Sci Ctr, Beijing 100191, Peoples R China
2.Chinese Univ Hong Kong, Sch Biomed Sci, Li Ka Shing Inst Hlth Sci, Inst Vasc Med, Hong Kong, Hong Kong, Peoples R China
3.Univ Hong Kong, Li Ka Shing Fac Med, Dept Physiol, Hong Kong, Hong Kong, Peoples R China
4.Xi An Jiao Tong Univ, Cardiovasc Res Ctr, Xian, Peoples R China

Recommended Citation:
Liu, Yahan,Tian, Xiao Yu,Mao, Guangmei,et al. Peroxisome Proliferator-Activated Receptor-gamma Ameliorates Pulmonary Arterial Hypertension by Inhibiting 5-Hydroxytryptamine 2B Receptor[J]. HYPERTENSION,2012,60(6):1471-U261.
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