Impact of dietary iron restriction on the development of monocrotaline-induced pulmonary vascular remodeling and right ventricular failure in rats

•We examine the effects of iron restriction on the development of pulmonary hypertension in rats.•Iron restriction reduces the development of monocrotaline-induced pulmonary hypertension.•The expression of cellular iron transporter was increased in the hypertensive pulmonary arteries.•The expression...

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Published in:Biochemical and biophysical research communications 2013-06, Vol.436 (2), p.145-151
Main Authors: Naito, Yoshiro, Hosokawa, Manami, Hao, Hiroyuki, Sawada, Hisashi, Hirotani, Shinichi, Iwasaku, Toshihiro, Okuhara, Yoshitaka, Eguchi, Akiyo, Hirota, Seiichi, Ohyanagi, Mitsumasa, Tsujino, Takeshi, Masuyama, Tohru
Format: Article
Language:English
Subjects:
Animals
Antimicrobial Cationic Peptides - genetics
Antimicrobial Cationic Peptides - metabolism
Gene Expression - drug effects
Hepcidins
Hypertension, Pulmonary - chemically induced
Hypertension, Pulmonary - physiopathology
Hypertrophy, Right Ventricular - chemically induced
Hypertrophy, Right Ventricular - physiopathology
Immunohistochemistry
Iron
Iron, Dietary - administration & dosage
Iron, Dietary - pharmacology
Kaplan-Meier Estimate
Lung - drug effects
Lung - metabolism
Lung - physiopathology
Male
Monocrotaline
Pulmonary Artery - drug effects
Pulmonary Artery - metabolism
Pulmonary Artery - physiopathology
Pulmonary hypertension
Random Allocation
Rats
Rats, Sprague-Dawley
Receptors, Transferrin - genetics
Receptors, Transferrin - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Right ventricular failure
Transferrin receptor 1
Ventricular Dysfunction, Right - chemically induced
Ventricular Dysfunction, Right - physiopathology
Ventricular Function, Right - drug effects
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Summary:•We examine the effects of iron restriction on the development of pulmonary hypertension in rats.•Iron restriction reduces the development of monocrotaline-induced pulmonary hypertension.•The expression of cellular iron transporter was increased in the hypertensive pulmonary arteries.•The expression of cellular iron transporter was increased in the hypertrophied right ventricle.•The gene expression of a key iron regulator was increased in the hypertrophied right ventricle. 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2013.05.059