Transferrin Receptor 1 in Chronic Hypoxia-Induced Pulmonary Vascular Remodeling
| Autor: | Yoshitaka Okuhara, Takeshi Tsujino, Hisashi Sawada, Toshiaki Mano, Akiyo Eguchi, Manami Hosokawa, Daisuke Morisawa, Toshihiro Iwasaku, Shinichi Hirotani, Yuko Soyama, Kenichi Fujii, Tohru Masuyama, Koichi Nishimura, Yoshiro Naito, Makiko Oboshi, Masaharu Ishihara |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Pathology Lung business.industry Transferrin receptor 030204 cardiovascular system & hematology Hypoxia (medical) medicine.disease Pulmonary hypertension 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology medicine.anatomical_structure Blood pressure Right ventricular hypertrophy medicine.artery Internal medicine Knockout mouse Pulmonary artery Internal Medicine medicine medicine.symptom business |
| Zdroj: | American Journal of Hypertension. 29:713-718 |
| ISSN: | 1941-7225 0895-7061 |
| DOI: | 10.1093/ajh/hpv163 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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