Iron Deficiency Induces Heart Failure with Ectopic Cardiac Calcification in Mice with Metabolic Syndrome
Iron Deficiency Induces Heart Failure with Ectopic Cardiac Calcification in Mice with Metabolic Syndrome
Abstract Iron deficiency is linked to worse clinical status and outcomes in heart failure. Although metabolic syndrome contributes to the development of heart failure, the impact of iron deficiency in heart failure complicated with metabolic syndrome remains obscure. KKAy mice were used as a model of metabolic syndrome. Four-week-old male C57BL/6J and KKAy mice were fed either a normal diet or iron-restricted (IR) diet for 12 weeks. During the experiment, 40% of mice died due to pulmonary congestion in KKAy mice with IR diet (KKAy-IR), while no mice died in other groups. Necropsy showed the presence of multiple white lesions on the cardiac surface in those KKAy-IR mice. Echocardiography and histological analyses revealed that KKAy-IR mice exhibited cardiac hypertrophy and cardiac dysfunction with cardiac calcification. Cardiac mRNA of ectonucleotide pyrophosphatase/phosphodiesterase-1 (Enpp1), a key enzyme for bone mineralization, was highly abundant in KKAy-IR mice. Of note, iron restriction-induced cardiac calcification and dysfunction were attenuated by etidronate, an inhibitor of bone mineralization, with decreased cardiac Enpp1 mRNA abundance in KKAy-IR mice. In conclusion, iron deficiency leads to ectopic cardiac calcification and dysfunction with the increase of Enpp1 in metabolic syndrome model mice.
Nishimura Koichi、Masuyama Tohru、Yasumura Seiki、Tsujino Takeshi、Tahara Saki、Asakura Masanori、Sawada Hisashi、Naito Yoshiro、Ishihara Masaharu、Horimatsu Tetsuo、Okuno Keisuke
Department of Cardiovascular and Renal Medicine, Hyogo College of MedicineDepartment of Cardiovascular and Renal Medicine, Hyogo College of Medicine||Japan Community Health care Organization, Hoshigaoka Medical CenterDepartment of Cardiovascular and Renal Medicine, Hyogo College of MedicineDepartment of Cardiovascular and Renal Medicine, Hyogo College of Medicine||Division of Pharmaceutical Therapeutics, Department of Pharmacy, School of Pharmacy, Hyogo University of Health SciencesDepartment of Cardiovascular and Renal Medicine, Hyogo College of MedicineDepartment of Cardiovascular and Renal Medicine, Hyogo College of MedicineDepartment of Cardiovascular and Renal Medicine, Hyogo College of Medicine||Saha Cardiovascular Research Center, College of Medicine, University of Kentucky||Saha Aortic Center, College of Medicine, University of Kentucky||Department of Physiology, College of Medicine, University of KentuckyDepartment of Cardiovascular and Renal Medicine, Hyogo College of MedicineDepartment of Cardiovascular and Renal Medicine, Hyogo College of MedicineDepartment of Cardiovascular and Renal Medicine, Hyogo College of MedicineDepartment of Cardiovascular and Renal Medicine, Hyogo College of Medicine
基础医学内科学生理学
anemiacardiac calcificationmetabolic syndromeiron deficiencyheart failure
Nishimura Koichi,Masuyama Tohru,Yasumura Seiki,Tsujino Takeshi,Tahara Saki,Asakura Masanori,Sawada Hisashi,Naito Yoshiro,Ishihara Masaharu,Horimatsu Tetsuo,Okuno Keisuke.Iron Deficiency Induces Heart Failure with Ectopic Cardiac Calcification in Mice with Metabolic Syndrome[EB/OL].(2025-03-28)[2025-05-11].https://www.biorxiv.org/content/10.1101/2022.01.20.477010.点此复制
评论