Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Biochem Biophys Res Commun. 2013 Jun 28;436(2):145-51. doi: 10.1016/j.bbrc.2013.05.059. Epub 2013 May 23.
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.
肺动脉高压（PH）的特征是肺血管重构导致右心室（RV）衰竭。最近，有报道称 PH 患者普遍存在铁缺乏。然而，PH 患者发生铁缺乏的机制尚不清楚。在这里，我们研究了饮食中铁限制对野百合碱诱导的肺血管重构的发展及其涉及的机制的影响。雄性 Sprague-Dawley 大鼠皮下注射野百合碱（60mg/kg）。之后，将野百合碱注射大鼠随机分为两组，分别给予正常饮食（n=6）或铁限制饮食（n=6）4 周。给予正常饮食的盐水注射大鼠作为对照（n=6）。野百合碱注射大鼠 4 周后表现出肺血管重构、RV 压力升高、RV 肥厚和 RV 射血分数降低，随后出现 RV 衰竭。相比之下，铁限制减轻了肺血管重构和 RV 衰竭的发展。有趣的是，与对照组相比，野百合碱注射大鼠的肺重构动脉和衰竭右心室中铁细胞转运蛋白转铁蛋白受体 1 的表达增加。此外，铁稳态的关键调节因子铁调素基因在野百合碱注射大鼠的衰竭右心室中表达增加。铁限制减轻了野百合碱诱导的肺血管重构和 RV 衰竭的发展。细胞铁转运可能参与 PH 和 PH 诱导的 RV 衰竭的病理生理学。
