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

TitleResident PW1+ Progenitor Cells Participate in Vascular Remodeling During Pulmonary Arterial Hypertension.
Publication TypeJournal Article
Year of Publication2016
AuthorsDierick F, Héry T, Hoareau-Coudert B, Mougenot N, Monceau V, Claude C, Crisan M, Besson V, Dorfmüller P, Marodon G, Fadel E, Humbert M, Yaniz-Galende E, Hulot J-S, Marazzi G, Sassoon D, Soubrier F, Nadaud S
JournalCirc Res
Date Published2016 Mar 4
KeywordsAnimals, Cells, Cultured, Humans, Hypertension, Pulmonary, Kruppel-Like Transcription Factors, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Smooth, Vascular, Rats, Stem Cells, Vascular Remodeling

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.

Alternate JournalCirc. Res.
PubMed ID26838788
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