Abstract 12816: Cellular Iron Transport Protein, Transferrin Receptor 1 Plays a Role in the Pathophysiology of Pulmonary Arterial Hypertension
Introduction: Cellular iron transport protein, transferrin receptor 1 (TfR1) is required for the uptake of transferrin-bound iron into the cells. Some reports have shown that iron deficiency is reported to be prevalent in patients with pulmonary arterial hypertension (PAH); however, the role of TfR1 in the pathophysiology of PAH remains unknown.
Hypothesis: We hypothesiged that TfR1 plays a role in the pathophysiology of PAH. Here, we investigate TfR1 in the experimental models of PAH.
Methods: Male Sprague-Dawley rats were subcutaneously injected with monocrotaline (60 mg/kg). Saline-injected rats were served as controls. In addition, we knocked down TfR1 expression in human pulmonary arterial smooth muscle cells (hPASMCs) and primary cardiomyocytes prepared from neonatal rats using its siRNA.
Results: Monocrotaline-injected rats showed pulmonary vascular remodeling, increased right ventricular pressure, and right ventricular hypertrophy. Of interest, TfR1 expression was increased in the pulmonary remodeled artery and the hypertrophied right ventricle of monocrotaline-injected rats, as compared with the controls. Meanwhile, iron content did not differ in the pulmonary artery and right ventricle between the control and monocrotaline-injected rats. Transfection of hPASMCs and cardiomyocytes with TfR1 siRNA significantly reduced TfR1 gene expression. Importantly, TfR1 silencing suppressed platelet-derived growth factor (PDGF)-induced proliferation of hPASMCs. Moreever, TfR1 silencing attenuated phenylephrine-induced increase in cell size of cardiomyocytes.
Conclusions: These results indicate that TfR1 plays a role in the pathophysiology of pulmonary artery remodeling and right ventricular hypertrophy in PAH.
Author Disclosures: M. Hosokawa: None. Y. Naito: None. H. Sawada: None. M. Oboshi: None. T. Iwasaku: None. Y. Okuhara: None. D. Morisawa: None. A. Eguchi: None. S. Hirotani: None. T. Mano: None. T. Tsujino: None. T. Masuyama: None.
- © 2014 by American Heart Association, Inc.