Iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice.
Several recent observations provide the association of iron deficiency with pulmonary hypertension (PH) in human and animal studies. However, it remains completely unknown whether PH leads to iron deficiency or iron deficiency enhances the development of PH. In addition, it is obscure whether iron is associated with the development of pulmonary vascular remodeling in PH. In this study, we investigate the impacts of dietary iron restriction on the development of hypoxia-induced pulmonary vascular remodeling in mice. Eight- to ten-week-old male C57BL/6J mice were exposed to chronic hypoxia for 4 weeks. Mice exposed to hypoxia were randomly divided into two groups and were given a normal diet or an iron-restricted diet. Mice maintained in room air served as normoxic controls. Chronic hypoxia induced pulmonary vascular remodeling, while iron restriction led a modest attenuation of this change. In addition, chronic hypoxia exhibited increased RV systolic pressure, which was attenuated by iron restriction. Moreover, the increase in RV cardiomyocyte cross-sectional area and RV interstitial fibrosis was observed in mice exposed to chronic hypoxia. In contrast, iron restriction suppressed these changes. Consistent with these changes, RV weight to left ventricular + interventricular septum weight ratio was increased in mice exposed to chronic hypoxia, while this increment was inhibited by iron restriction. Taken together, these results suggest that iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice.
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan. ynaito@hyo-med.ac.jp.
Yoshiro
Y
Naito
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Manami
M
Hosokawa
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Hisashi
H
Sawada
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Makiko
M
Oboshi
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Toshihiro
T
Iwasaku
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Yoshitaka
Y
Okuhara
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Akiyo
A
Eguchi
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Koichi
K
Nishimura
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Yuko
Y
Soyama
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Shinichi
S
Hirotani
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Toshiaki
T
Mano
Division of Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Masaharu
M
Ishihara
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Tohru
T
Masuyama
D000818:Animals; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D066253:Vascular Remodeling; D018497:Ventricular Dysfunction, Right / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016278:Ventricular Function, Right; D020257:Ventricular Remodeling
D019266:Iron, Dietary; D007501:Iron
Iron; Pulmonary hypertension; Right ventricular failure