Sildenafil attenuates hypoxic pulmonary remodelling by inhibiting bone marrow progenitor cells.

Détails

Ressource 1Télécharger: Favre_et_al-2017-Journal_of_Cellular_and_Molecular_Medicine.pdf (1004.42 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_BB5BD3229159
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Sildenafil attenuates hypoxic pulmonary remodelling by inhibiting bone marrow progenitor cells.
Périodique
Journal of cellular and molecular medicine
Auteur(s)
Favre S., Gambini E., Nigro P., Scopece A., Bianciardi P., Caretti A., Pompilio G., Corno A.F., Vassalli G., von Segesser L.K., Samaja M., Milano G.
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
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
Données d'usage