Bone marrow-derived progenitor cells contribute to the pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension

Abstract Circulating BM-derived progenitor cells (PCs) might preserve the ability to differentiate into endothelial cells (ECs) or smooth-muscle cells (SMCs) and be involved in postnatal neovascularization and the pathogenesis of various vascular diseases. To elucidate the role of circulating PCs in the pathogenesis of pulmonary hypertension (PH), we used hypoxia-induced PH model in chimeric mice. BM cells were purified from Rosa26 transgenic mice that ubiquitously express lacZ (b-gal) gene and were transplanted into the lethally irradiated wild-type mice. Four weeks after the BM transplantation, these mice were exposed to hypoxia (FiO 2  = 0.1) for 5 weeks. Both the right ventricular (RV) systolic pressure and gravimetric index for RV hypertrophy (RV/LV + septum) were higher in the hypoxic mice than in the normoxic mice(34 ± 3mmHg vs 21 ± 3mmHg and 0.37 ± 0.03 vs 0.25 ± 0.03, respectively, p