Impact of dietary iron restriction on the development of monocrotaline-induced pulmonary vascular remodeling and right ventricular failure in rats
| Autor: | Takeshi Tsujino, Tohru Masuyama, Yoshitaka Okuhara, Shinichi Hirotani, Manami Hosokawa, Yoshiro Naito, Akiyo Eguchi, Hiroyuki Hao, Toshihiro Iwasaku, Hisashi Sawada, Seiichi Hirota, Mitsumasa Ohyanagi |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Normal diet Hypertension Pulmonary Ventricular Dysfunction Right Biophysics Gene Expression Transferrin receptor Kaplan-Meier Estimate Pulmonary Artery Biology Biochemistry Rats Sprague-Dawley Random Allocation Hepcidins Hepcidin Internal medicine Receptors Transferrin medicine Animals Lung Molecular Biology Monocrotaline Ejection fraction Hypertrophy Right Ventricular Reverse Transcriptase Polymerase Chain Reaction Cell Biology Iron deficiency medicine.disease Immunohistochemistry Pulmonary hypertension Rats medicine.anatomical_structure Endocrinology Ventricle Ventricular Function Right biology.protein Iron Dietary Antimicrobial Cationic Peptides Artery |
| Zdroj: | Biochemical and Biophysical Research Communications. 436:145-151 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2013.05.059 |
| Popis: | 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 (60 mg/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 4 weeks. 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 4 weeks. 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. |
| Databáze: | OpenAIRE |
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