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• W2340395783 abstract "Abstract Pulmonary arterial hypertension (PAH) is a progressive lung disease of the pulmonary microvasculature. Recent studies suggest that bone marrow (BM)-derived circulating cells may play an important role in its pathogenesis. We used a genetic model of PAH, the Bmpr2 mutant mouse, to study the role of bone marrow-derived circulating cells in its pathogenesis. Recipient mice, either Bmpr2R899X mutant or controls, were lethally irradiated and transplanted with either control or Bmpr2R899X BM cells. Donor cells were traced in female recipient mice by Y chromosome painting. Molecular and function insights were provided by expression and cytokine arrays combined with flow cytometry, colony forming and competitive transplant assays. We found that mutant BM cells caused pulmonary arterial hypertension with remodeling and inflammation when transplanted into control mice, while control BM cells had a protective effect against the development of disease, when transplanted into mutant mice. Donor BM derived cells were present in the lungs of recipient mice. Functional and molecular analysis identified mutant BM cells dysfunction suggestive of a PAH phenotype soon after activation of the transgene and long before the development of lung pathology. Our data show that BM cells played key role in PAH pathogenesis and given that the transplanted BM cells were able to drive the lung phenotype. Furthermore the specific cell types involved were derived from HSCs and exhibit dysfunction long before the development of lung pathology." @default.
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• W2340395783 date "2015-12-09" @default.
• W2340395783 modified "2023-09-25" @default.
• W2340395783 title "Bone Marrow-derived Cells Contribute to Pathogenesis of Pulmonary Arterial Hypertension." @default.
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