TY - JOUR
T1 - Transferrin Receptor 1 in Chronic Hypoxia-Induced Pulmonary Vascular Remodeling
AU - Naito, Yoshiro
AU - Hosokawa, Manami
AU - Sawada, Hisashi
AU - Oboshi, Makiko
AU - Hirotani, Shinichi
AU - Iwasaku, Toshihiro
AU - Okuhara, Yoshitaka
AU - Morisawa, Daisuke
AU - Eguchi, Akiyo
AU - Nishimura, Koichi
AU - Soyama, Yuko
AU - Fujii, Kenichi
AU - Mano, Toshiaki
AU - Ishihara, Masaharu
AU - Tsujino, Takeshi
AU - Masuyama, Tohru
N1 - Publisher Copyright:
© 2015 American Journal of Hypertension, Ltd 2015. All rights reserved.
PY - 2016/6/20
Y1 - 2016/6/20
N2 - 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.
AB - 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.
KW - blood pressure
KW - pulmonary hypertension
KW - right ventricular hypertrophy
KW - transferrin receptor 1
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U2 - 10.1093/ajh/hpv163
DO - 10.1093/ajh/hpv163
M3 - Article
C2 - 26419445
AN - SCOPUS:84973483685
SN - 0895-7061
VL - 29
SP - 713
EP - 718
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 6
ER -
