Lung Progenitor Cells Expressing PW1 Gene Participate in Vascular Remodeling During Pulmonary Arterial Hypertension

AIM: PW1+ progenitors were identified in adult tissues and can differentiate in smooth muscle cells (SMC) in vitro. Our hypothesis is that PW1+ progenitors are recruited to participate in the vascular remodeling during pulmonary hypertension (PAH). METHODS: PW1IRESnLacZ+/- mice express the β-galactosidase as a reporter gene for PW1 expression allowing to follow the lineage of PW1+ cells. These mice were exposed to chronic hypoxia (CH) to induce PAH and lung vessels neomuscularisation. RESULTS: In rodent and human lung, PW1+ cells were adjacent to small vessels. They express c-Kit, PDGFRα and pericyte markers and differentiate in vitro into SMC. After 4 days of CH, proliferating lung PW1+ cells were increased (x3, p<0.01) as well as PDGFR-α+/PW1+ and c-Kit+/PW1+ cells (x2 and x8, p<0.001). In small pulmonary vessels, the proportion of β-Gal+ vascular SMC derived from PW1+ cells was increased (64% vs 35%, p<0.05) suggesting a recruitment and differentiation of PW1+ cells into lung vascular SMC. Moreover, WT...