Academic Journal
Sildenafil Attenuates Hypoxic Pulmonary Remodelling by Inhibiting Bone Marrow Progenitor Cells
| العنوان: | Sildenafil Attenuates Hypoxic Pulmonary Remodelling by Inhibiting Bone Marrow Progenitor Cells |
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| المؤلفون: | Favre, Shirley, Gambini, Elisa, Nigro, Patrizia, Scopece, Alessandro, Bianciardi, Paola, Caretti, Anna, Pompilio, Giulio, Corno, Antonio F, Vassalli, Giuseppe, von Segesser, Ludwig K, Samaja, Michele, Milano, Giuseppina |
| المصدر: | Favre, Shirley; Gambini, Elisa; Nigro, Patrizia; Scopece, Alessandro; Bianciardi, Paola; Caretti, Anna; Pompilio, Giulio; Corno, Antonio F; Vassalli, Giuseppe; von Segesser, Ludwig K; Samaja, Michele; Milano, Giuseppina (2017). Sildenafil Attenuates Hypoxic Pulmonary Remodelling by Inhibiting Bone Marrow Progenitor Cells. Journal of Cellular and Molecular Medicine, 21(5):871-880. |
| بيانات النشر: | Wiley Open Access |
| سنة النشر: | 2017 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Clinic for Cardiac Surgery, Cardiocentro Ticino, 610 Medicine & health, CXCR4 receptor, bone marrow progenitor cells, c-kit cells, chronic hypoxia, pulmonary Hypertension, sildenafil |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1582-1838 |
| Relation: | https://www.zora.uzh.ch/id/eprint/144305/1/Favre_et_al-2017-Journal_of_Cellular_and_Molecular_Medicine.pdf; info:pmid/27860185; urn:issn:1582-1838 |
| DOI: | 10.1111/jcmm.13026 |
| الاتاحة: | https://www.zora.uzh.ch/id/eprint/144305/ https://doi.org/10.1111/jcmm.13026 |
| Rights: | info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.F217CF55 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15821838 |
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| DOI: | 10.1111/jcmm.13026 |