Sildenafil attenuates hypoxic pulmonary remodelling by inhibiting bone marrow progenitor cells.
Détails
Télécharger: Favre_et_al-2017-Journal_of_Cellular_and_Molecular_Medicine.pdf (1004.42 [Ko])
Etat: Public
Version: Final published version
Etat: Public
Version: Final published version
ID Serval
serval:BIB_BB5BD3229159
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Sildenafil attenuates hypoxic pulmonary remodelling by inhibiting bone marrow progenitor cells.
Périodique
Journal of cellular and molecular medicine
ISSN
1582-4934 (Electronic)
ISSN-L
1582-1838
Statut éditorial
Publié
Date de publication
05/2017
Peer-reviewed
Oui
Volume
21
Numéro
5
Pages
871-880
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
The recruitment of bone marrow (BM)-derived progenitor cells to the lung is related to pulmonary remodelling and the pathogenesis of pulmonary hypertension (PH). Although sildenafil is a known target in PH treatment, the underlying molecular mechanism is still elusive. To test the hypothesis that the therapeutic effect of sildenafil is linked to the reduced recruitment of BM-derived progenitor cells, we induced pulmonary remodelling in rats by two-week exposure to chronic hypoxia (CH, 10% oxygen), a trigger of BM-derived progenitor cells. Rats were treated with either placebo (saline) or sildenafil (1.4 mg/kg/day ip) during CH. Control rats were kept in room air (21% oxygen) with no treatment. As expected, sildenafil attenuated the CH-induced increase in right ventricular systolic pressure and right ventricular hypertrophy. However, sildenafil suppressed the CH-induced increase in c-kit(+) cells in the adventitia of pulmonary arteries. Moreover, sildenafil reduced the number of c-kit(+) cells that colocalize with tyrosine kinase receptor 2 (VEGF-R2) and CD68 (a marker for macrophages), indicating a positive effect on moderating hypoxia-induced smooth muscle cell proliferation and inflammation without affecting the pulmonary levels of hypoxia-inducible factor (HIF)-1α. Furthermore, sildenafil depressed the number of CXCR4(+) cells. Collectively, these findings indicate that the improvement in pulmonary haemodynamic by sildenafil is linked to decreased recruitment of BM-derived c-kit(+) cells in the pulmonary tissue. The attenuation of the recruitment of BM-derived c-kit(+) cells by sildenafil may provide novel therapeutic insights into the control of pulmonary remodelling.
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/12/2016 22:51
Dernière modification de la notice
20/08/2019 16:29