title: Impact of dietary iron restriction on the development of monocrotaline-induced pulmonary vascular remodeling and right ventricular failure in rats.
abstract: Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling leading to right ventricular (RV) failure. Recently, iron deficiency is reported to be prevalent in patients with PH. However, the mechanism by which iron deficiency occurs in patients with PH remains unknown. Here, we investigated the effects of dietary iron restriction on the development of monocrotaline-induced pulmonary vascular remodeling and the involved mechanisms. Male Sprague-Dawley rats were subcutaneously injected with monocrotaline (60mg/kg). Afterwards, monocrotaline-injected rats were randomly divided into two groups and were given a normal diet (n=6) or an iron-restricted diet (n=6) for 4weeks. Saline-injected rats given a normal diet were served as controls (n=6). Monocrotaline-injected rats showed pulmonary vascular remodeling, increased RV pressure, RV hypertrophy, and decreased RV ejection fraction, followed by RV failure after 4weeks. In contrast, iron restriction attenuated the development of pulmonary vascular remodeling and RV failure. Of interest, expression of cellular iron transport protein, transferrin receptor 1 was increased in the pulmonary remodeled artery and the failing right ventricle of monocrotaline-injected rats, as compared with the controls. Moreover, a key regulator of iron homeostasis, hepcidin gene expression was increased in the failing right ventricle of monocrotaline-injected rats. Iron restriction attenuated the development of monocrotaline-induced pulmonary vascular remodeling and RV failure. Cellular iron transport might be involved in the pathophysiology of PH and PH induced RV failure.
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.forename: Manami
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hao
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sawada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Iwasaku
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okuhara
authors.forename: Akiyo
authors.initials: A
authors.lastname: Eguchi
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Ohyanagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D064451:Hepcidins; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology*; D007150:Immunohistochemistry; D019266:Iron, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced / Q000503:physiopathology*; D016278:Ventricular Function, Right / Q000187:drug effects
chemical_list: D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; C578703:Hamp protein, rat; D064451:Hepcidins; D019266:Iron, Dietary; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; D016686:Monocrotaline