0074 : Resident PW1+ progenitor cells participate in vascular remodeling during pulmonary arterial hypertension

Rationale Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and neomuscularization. PW1+ progenitor cells can differentiate into smooth muscle cells (SMC) in vitro. Objective To determine the role of pulmonary PW1+ progenitor cells in vascular remodeling characteristic of PAH. Methods and results We investigated their contribution during chronic hypoxia (CH)-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, three distinct myogenic PW1+ cell populations were isolated from the mouse lung of which two were significantly increased after 4 days of CH. 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 CH-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 (MCT) injection. In the human PAH lung, 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 PAHassociated vascular remodeling. The author hereby declares no conflict of interest