Iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice

Yoshiro Naito, Manami Hosokawa, Hisashi Sawada, Makiko Oboshi, Toshihiro Iwasaku, Yoshitaka Okuhara, Akiyo Eguchi, Koichi Nishimura, Yuko Soyama, Shinichi Hirotani, Toshiaki Mano, Masaharu Ishihara, Tohru Masuyama

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2074-2079
Number of pages6
JournalHeart and Vessels
Volume31
Issue number12
DOIs
StatePublished - Dec 1 2016

Bibliographical note

Publisher Copyright:
© 2016, Springer Japan.

Keywords

  • Iron
  • Pulmonary hypertension
  • Right ventricular failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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