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

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 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.