TY - JOUR
T1 - Iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice
AU - Naito, Yoshiro
AU - Hosokawa, Manami
AU - Sawada, Hisashi
AU - Oboshi, Makiko
AU - Iwasaku, Toshihiro
AU - Okuhara, Yoshitaka
AU - Eguchi, Akiyo
AU - Nishimura, Koichi
AU - Soyama, Yuko
AU - Hirotani, Shinichi
AU - Mano, Toshiaki
AU - Ishihara, Masaharu
AU - Masuyama, Tohru
N1 - Publisher Copyright:
© 2016, Springer Japan.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - Iron
KW - Pulmonary hypertension
KW - Right ventricular failure
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U2 - 10.1007/s00380-016-0860-8
DO - 10.1007/s00380-016-0860-8
M3 - Article
C2 - 27311944
AN - SCOPUS:84975748827
SN - 0910-8327
VL - 31
SP - 2074
EP - 2079
JO - Heart and Vessels
JF - Heart and Vessels
IS - 12
ER -