Peroxisome proliferator-activated receptor-ß/δ, the acute signaling factor in prostacyclin-induced pulmonary vasodilation.
Am J Respir Cell Mol Biol
; 46(3): 372-9, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22021335
ABSTRACT
As powerful vasodilators, prostacyclin analogues are presently the mainstay in the treatment of severe pulmonary arterial hypertension. Although the hemodynamic effects of prostacyclin analogues are well known, the molecular mechanism of their acute effects on pulmonary vascular tone and systemic vascular tone remains poorly understood. Peroxisome proliferator-activated receptor-ß/δ (PPARß/δ) was previously identified as a putative receptor responsible for the modulation of target gene expression in response to prostacyclin analogues. The present study investigated the signaling pathway of prostacyclin in human pulmonary arterial smooth muscle cells (PASMCs), and sought to define the role of PPARß/δ in the acute vasodilating effect. In human PASMCs, prostacyclin rapidly activated TWIK-related acid-sensitive K channel 1 (TASK-1) and calcium-dependent potassium channels (K(Ca)). This pathway was mediated via the prostanoid I receptor-protein kinase A pathway. The silencing of PPARß/δ demonstrated that the downstream K(Ca) activation was exclusively dependent on PPARß/δ signaling, whereas the activation of TASK-1 was not. In addition, the PPARß/δ-induced activation of K(Ca) was independent of NO. The acute prostacyclin-induced K(Ca) activation is critically dependent on PPARß/δ as a rapid signaling factor. This accounts in part for the vasodilating effect of prostacyclin in pulmonary arteries, and provides insights into a new molecular explanation for the effects of prostanoids.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatação
/
Vasodilatadores
/
Transdução de Sinais
/
Iloprosta
/
Epoprostenol
/
Canais de Potássio Cálcio-Ativados
/
Miócitos de Músculo Liso
/
PPAR delta
/
PPAR gama
/
Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Am J Respir Cell Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Áustria