Yoshiro Naito 1 , Manami Hosokawa 2 , Hisashi Sawada 2 , Makiko Oboshi 2 , Shinichi Hirotani 2 , Toshihiro Iwasaku 2 , Yoshitaka Okuhara 2 , Daisuke Morisawa 2 , Akiyo Eguchi 2 , Koichi Nishimura 2 , Yuko Soyama 2 , Kenichi Fujii 2 , Toshiaki Mano 2 , Masaharu Ishihara 3 , Takeshi Tsujino 4 , Tohru Masuyama 2 Show Affiliations »
Abstract
BACKGROUND: Iron is associated with the pathophysiology of several cardiovascular diseases, including pulmonary hypertension (PH). In addition, disrupted pulmonary iron homeostasis has been reported in several chronic lung diseases. Transferrin receptor 1 (TfR1) plays a key role in cellular iron transport. However, the role of TfR1 in the pathophysiology of PH has not been well characterized. In this study, we investigate the role of TfR1 in the development of hypoxia-induced pulmonary vascular remodeling. METHODS: PH was induced by exposing wild-type (WT) mice and TfR1 hetero knockout mice to hypoxia for 4 weeks and evaluated via assessment of pulmonary vascular remodeling, right ventricular (RV) systolic pressure, and RV hypertrophy. In addition, we assessed the functional role of TfR1 in pulmonary artery smooth muscle cells in vitro. RESULTS: The morphology of pulmonary arteries did not differ between WT mice and TfR1 hetero knockout mice under normoxic conditions. In contrast, TfR1 hetero knockout mice exposed to 4 weeks hypoxia showed attenuated pulmonary vascular remodeling, RV systolic pressure, and RV hypertrophy compared with WT mice. In addition, the depletion of TfR1 by RNA interference attenuated human pulmonary artery smooth muscle cells proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in vitro. CONCLUSIONS: These results suggest that TfR1 plays an important role in the development of hypoxia-induced pulmonary vascular remodeling. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
BACKGROUND: Iron is associated with the pathophysiology of several cardiovascular diseases , including pulmonary hypertension (PH). In addition, disrupted pulmonary iron homeostasis has been reported in several chronic lung diseases . Transferrin receptor 1 (TfR1 ) plays a key role in cellular iron transport. However, the role of TfR1 in the pathophysiology of PH has not been well characterized. In this study, we investigate the role of TfR1 in the development of hypoxia-induced pulmonary vascular remodeling . METHODS: PH was induced by exposing wild-type (WT) mice and TfR1 hetero knockout mice to hypoxia for 4 weeks and evaluated via assessment of pulmonary vascular remodeling , right ventricular (RV) systolic pressure, and RV hypertrophy . In addition, we assessed the functional role of TfR1 in pulmonary artery smooth muscle cells in vitro. RESULTS: The morphology of pulmonary arteries did not differ between WT mice and TfR1 hetero knockout mice under normoxic conditions. In contrast, TfR1 hetero knockout mice exposed to 4 weeks hypoxia showed attenuated pulmonary vascular remodeling , RV systolic pressure, and RV hypertrophy compared with WT mice . In addition, the depletion of TfR1 by RNA interference attenuated human pulmonary artery smooth muscle cells proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in vitro. CONCLUSIONS: These results suggest that TfR1 plays an important role in the development of hypoxia-induced pulmonary vascular remodeling . © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Entities: Chemical
Disease
Gene
Species
Keywords:
blood pressure; pulmonary hypertension; right ventricular hypertrophy; transferrin receptor 1.
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Year: 2015
PMID： 26419445 DOI： 10.1093/ajh/hpv163
Source DB: PubMed Journal: Am J Hypertens ISSN： 0895-7061 Impact factor: 2.689