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Circ Res. 2016 Mar 4;118(5):822-33. doi: 10.1161/CIRCRESAHA.115.307035. Epub 2016 Jan 12.

Resident PW1+ Progenitor Cells Participate in Vascular Remodeling During Pulmonary Arterial Hypertension.

Author information

1
From the INSERM, Institute of Cardiometabolism and Nutrition, UMR_S 1166-ICAN (F.D., T.H., V.M., C.C., V.B., E.Y.-G., J.-S.H., G.M., D.S., F.S., S.N.), UMS-030 CyPS, Paris, France (B.H.-C.), PECMV UMS28 (N.M.), INSERM, CNRS, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI), U1135, ERL 8255 (G.M.), Sorbonne Universités, UPMC Univ Paris 06, Paris, France; Erasmus MC Stem Cell Institute, Rotterdam, The Netherlands (M.C.); Univ Paris-Sud, Université Paris Saclay, INSERM UMR-S 999, Labex LERMIT, Le Plessis-Robinson, Paris, France (P.D., E.F., M.H.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France (P.D.); Service de Chirurgie Thoracique et Vasculaire, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Univ Paris-Sud, Université Paris Saclay, Le Kremlin-Bicêtre, Paris, France (M.H.); and Assistance Publique Hôpitaux de Paris, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, Hôpital Bicêtre, Le Kremlin Bicêtre, France (M.H.).
2
From the INSERM, Institute of Cardiometabolism and Nutrition, UMR_S 1166-ICAN (F.D., T.H., V.M., C.C., V.B., E.Y.-G., J.-S.H., G.M., D.S., F.S., S.N.), UMS-030 CyPS, Paris, France (B.H.-C.), PECMV UMS28 (N.M.), INSERM, CNRS, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI), U1135, ERL 8255 (G.M.), Sorbonne Universités, UPMC Univ Paris 06, Paris, France; Erasmus MC Stem Cell Institute, Rotterdam, The Netherlands (M.C.); Univ Paris-Sud, Université Paris Saclay, INSERM UMR-S 999, Labex LERMIT, Le Plessis-Robinson, Paris, France (P.D., E.F., M.H.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France (P.D.); Service de Chirurgie Thoracique et Vasculaire, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Univ Paris-Sud, Université Paris Saclay, Le Kremlin-Bicêtre, Paris, France (M.H.); and Assistance Publique Hôpitaux de Paris, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, Hôpital Bicêtre, Le Kremlin Bicêtre, France (M.H.). sophie.nadaud@upmc.fr.

Abstract

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 Pw1(nLacZ+/-) 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.

KEYWORDS:

adult stem cells; hypertension, pulmonary; hypoxia; muscle, smooth, vascular; vascular remodeling

PMID:
26838788
DOI:
10.1161/CIRCRESAHA.115.307035
[Indexed for MEDLINE]

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