Peroxisome proliferator-activated receptor-γ ameliorates pulmonary arterial hypertension by inhibiting 5-Hydroxytryptamine 2B receptor

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Yahan Liu
  • Xiao Yu Tian
  • Guangmei Mao
  • Xi Fang
  • Man Lung Fung
  • John Y.-J. Shyy
  • Nanping Wang

Detail(s)

Original languageEnglish
Pages (from-to)1471-1478
Journal / PublicationHypertension
Volume60
Issue number6
Publication statusPublished - Dec 2012
Externally publishedYes

Abstract

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-γ (PPARγ) 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 PPARγ 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 PPARγ 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 PPARγ. The pharmacological effect of PPARγ was through the suppression of the 5-HT-induced activator protein-1 activity. These results demonstrated the beneficial effect of PPARγ on 5-HT2BR-mediated vasocontraction, providing a new mechanism for the potential use of PPARγ agonists in PAH. © 2012 American Heart Association, Inc.

Research Area(s)

  • 5-hydroxytryptamine 2B receptor, peroxisome proliferator-activated receptor-γ, pulmonary arterial hypertension, vasoconstriction

Bibliographic Note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

Citation Format(s)

Peroxisome proliferator-activated receptor-γ ameliorates pulmonary arterial hypertension by inhibiting 5-Hydroxytryptamine 2B receptor. / Liu, Yahan; Tian, Xiao Yu; Mao, Guangmei et al.
In: Hypertension, Vol. 60, No. 6, 12.2012, p. 1471-1478.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review