title: Transferrin Receptor 1 in Chronic Hypoxia-Induced Pulmonary Vascular Remodeling.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  These results suggest that TfR1 plays an important role in the development of hypoxia-induced pulmonary vascular remodeling.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan; ynaito@hyo-med.ac.jp.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Manami
authors.initials: M
authors.lastname: Hosokawa
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sawada
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Makiko
authors.initials: M
authors.lastname: Oboshi
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Iwasaku
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okuhara
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morisawa
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Akiyo
authors.initials: A
authors.lastname: Eguchi
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Yuko
authors.initials: Y
authors.lastname: Soyama
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Kenichi
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mano
authors.affiliation: Division of Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Department of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan;
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000818:Animals; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D011651:Pulmonary Artery / Q000473:pathology; D011990:Receptors, Transferrin / Q000502:physiology*; D066253:Vascular Remodeling
chemical_list: D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse
keywords: blood pressure; pulmonary hypertension; right ventricular hypertrophy; transferrin receptor 1.