Your browser doesn't support javascript.
loading
Protective Role of Myelocytic Nitric Oxide Synthases against Hypoxic Pulmonary Hypertension in Mice.
Ogoshi, Takaaki; Tsutsui, Masato; Kido, Takashi; Sakanashi, Mayuko; Naito, Keisuke; Oda, Keishi; Ishimoto, Hiroshi; Yamada, Sohsuke; Wang, Ke-Yong; Toyohira, Yumiko; Izumi, Hiroto; Masuzaki, Hiroaki; Shimokawa, Hiroaki; Yanagihara, Nobuyuki; Yatera, Kazuhiro; Mukae, Hiroshi.
Afiliação
  • Ogoshi T; 1 Department of Respiratory Medicine.
  • Tsutsui M; 2 Department of Pharmacology and.
  • Kido T; 1 Department of Respiratory Medicine.
  • Sakanashi M; 2 Department of Pharmacology and.
  • Naito K; 1 Department of Respiratory Medicine.
  • Oda K; 1 Department of Respiratory Medicine.
  • Ishimoto H; 1 Department of Respiratory Medicine.
  • Yamada S; 3 Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; and.
  • Wang KY; 4 Department of Pathology, and.
  • Toyohira Y; 5 Shared-Use Research Center and.
  • Izumi H; 6 Department of Pharmacology, School of Medicine, and.
  • Masuzaki H; 7 Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.
  • Shimokawa H; 8 Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
  • Yanagihara N; 9 Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • Yatera K; 6 Department of Pharmacology, School of Medicine, and.
  • Mukae H; 1 Department of Respiratory Medicine.
Am J Respir Crit Care Med ; 198(2): 232-244, 2018 07 15.
Article em En | MEDLINE | ID: mdl-29480750
RATIONALE: 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. OBJECTIVES: To determine the role of NOSs in BM cells in PH. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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 in the n/i/eNOSs-/- genotype. A total of 69 and 49 mRNAs related to immunity and inflammation, respectively, were significantly upregulated in the lungs of WT genotype mice transplanted with n/i/eNOSs-/--BM compared with those with WT-BM, suggesting the involvement of immune and inflammatory mechanisms in the exacerbation of hypoxia-induced PH caused by n/i/eNOSs-/--BM transplantation. CONCLUSIONS: These results demonstrate that myelocytic n/i/eNOSs play an important protective role in the pathogenesis of PH.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células da Medula Óssea / Óxido Nítrico Sintase / Células Precursoras de Granulócitos / Hipertensão Pulmonar / Hipóxia Limite: Animals / Humans / Male Idioma: En Revista: Am J Respir Crit Care Med Assunto da revista: TERAPIA INTENSIVA Ano de publicação: 2018 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células da Medula Óssea / Óxido Nítrico Sintase / Células Precursoras de Granulócitos / Hipertensão Pulmonar / Hipóxia Limite: Animals / Humans / Male Idioma: En Revista: Am J Respir Crit Care Med Assunto da revista: TERAPIA INTENSIVA Ano de publicação: 2018 Tipo de documento: Article País de publicação: Estados Unidos