Protective Role of Myelocytic Nitric Oxide Synthases against Hypoxic Pulmonary Hypertension in Mice

American Journal of Respiratory and Critical Care Medicine
Takaaki OgoshiHiroshi Mukae

Abstract

Nitric oxide (NO), synthesized by NOSs (NO synthases), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive. To determine the role of NOSs in BM cells in PH. Experiments were performed on 36 patients with idiopathic pulmonary fibrosis and on wild-type (WT), nNOS (neuronal NOS)-/-, iNOS (inducible NOS)-/-, eNOS (endothelial NOS)-/-, and n/i/eNOSs-/- mice. In the patients, there was a significant correlation between higher pulmonary artery systolic pressure and lower nitrite plus nitrate levels in the BAL fluid. In the mice, hypoxia-induced PH deteriorated significantly in the n/i/eNOSs-/- genotype and, to a lesser extent, in the eNOS-/- genotype as compared with the WT genotype. In the n/i/eNOSs-/- genotype exposed to hypoxia, the number of circulating BM-derived vascular smooth muscle progenitor cells was significantly larger, and transplantation of green fluorescent protein-transgenic BM cells revealed the contribution of BM cells to pulmonary vascular remodeling. Importantly, n/i/eNOSs-/--BM transplantation significantly aggravated hypoxia-induced PH in the WT genotype, and WT-BM transplantation significantly ameliorated hypoxia-induced PH...Continue Reading

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Citations

Mar 3, 2020·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Takaaki OgoshiHiroshi Mukae
Aug 8, 2018·International Journal of Molecular Sciences·Andrew J BryantLyle L Moldawer
Mar 29, 2018·American Journal of Respiratory and Critical Care Medicine·Jarrod W Barnes, Rakesh P Patel

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Methods Mentioned

BETA
flow cytometry
nucleotide exchange

Software Mentioned

IPA
ingenuity pathways analysis ( IPA
Subio
DAVID

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