| Title: |
Resident PW1(+) Progenitor Cells Participate in Vascular Remodeling During Pulmonary Arterial Hypertension |
| Authors: |
Dierick, France; Héry, Tiphaine; Hoareau, Bénédicte; Mougenot, Nathalie; Monceau, Virginie; Claude, Caroline; Crisan, Mihaela; Besson, Vanessa; Dorfmüller, Peter; Marodon, Gilles; Fadel, Elie; Humbert, Marc; Yaniz-Galende, Elisa; Hulot, Jean-Sébastien; Marazzi, Giovanna; Sassoon, David; Soubrier, Florent; Nadaud, Sophie |
| Contributors: |
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN); Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU); Plateforme Cytométrie Pitié-Salpêtrière (LUMIC-CYPS); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Unité Mixte de Service d'Imagerie et de Cytométrie (UMS LUMIC); Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM); PECMV core; Université Pierre et Marie Curie - Paris 6 (UPMC); Erasmus University Medical Center Rotterdam (Erasmus MC); Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique (HPPIT); Université Paris-Sud - Paris 11 (UP11)-Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM); Service d’Anatomie Pathologique Centre Chirurgical Marie Lannelongue; Centre Chirurgical Marie Lannelongue (CCML); Centre d'Immunologie et de Maladies Infectieuses (CIMI); Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Service de Chirurgie Thoracique et Vasculaire Centre Chirurgical Marie Lannelongue; Université Paris-Saclay; Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Centre de Référence de l’Hypertension Pulmonaire Sévère CHU Le Kremlin Bicêtre; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre; ANR-15-CE14-0020,PAHVAP,IDENTIFIER LES DRIVERS DU RECRUTEMENT DES PROGENITEURS VASCULAIRES PULMONAIRES RESIDENTS QUI PARTICIPENT AU DEVELOPPEMENT DE L'HYPERTENSION ARTERIELLE PULMONAIRE(2015) |
| Source: |
ISSN: 0009-7330. |
| Publisher Information: |
CCSD; American Heart Association |
| Publication Year: |
2016 |
| Subject Terms: |
adult stem cells; hypertension; pulmonary; hypoxia; muscle; smooth; vascular; vascular remodeling; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Description: |
International audience ; Rationale: Pulmonary arterial hypertension is characterized by vascular remodeling and neomuscularization. PW1+ progenitor cells can differentiate into smooth muscle cells (SMCs) in vitro.Objective: To determine the role of pulmonary PW1+ progenitor cells in vascular remodeling characteristic of pulmonary arterial hypertension.Methods and Results: We investigated their contribution during chronic hypoxia–induced vascular remodeling in Pw1nLacZ+/− mouse expressing β-galactosidase in PW1+ cells and in differentiated cells derived from PW1+ cells. PW1+ progenitor cells are present in the perivascular zone in rodent and human control lungs. Using progenitor markers, 3 distinct myogenic PW1+ cell populations were isolated from the mouse lung of which 2 were significantly increased after 4 days of chronic hypoxia. The number of proliferating pulmonary PW1+ cells and the proportion of β-gal+ vascular SMC were increased, indicating a recruitment of PW1+ cells and their differentiation into vascular SMC during early chronic hypoxia–induced neomuscularization. CXCR4 inhibition using AMD3100 prevented PW1+ cells differentiation into SMC but did not inhibit their proliferation. Bone marrow transplantation experiments showed that the newly formed β-gal+ SMC were not derived from circulating bone marrow–derived PW1+ progenitor cells, confirming a resident origin of the recruited PW1+ cells. The number of pulmonary PW1+ cells was also increased in rats after monocrotaline injection. In lung from pulmonary arterial hypertension patients, PW1-expressing cells were observed in large numbers in remodeled vascular structures.Conclusions: These results demonstrate the existence of a novel population of resident SMC progenitor cells expressing PW1 and participating in pulmonary hypertension–associated vascular remodeling. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1161/CIRCRESAHA.115.307035 |
| Availability: |
https://hal.sorbonne-universite.fr/hal-01304194; https://hal.sorbonne-universite.fr/hal-01304194v1/document; https://hal.sorbonne-universite.fr/hal-01304194v1/file/Dierick_2016_Resident_PW1%28%2B%29.pdf; https://doi.org/10.1161/CIRCRESAHA.115.307035 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.C0F1851F |
| Database: |
BASE |