Iron Deficiency Induces Heart Failure With Ectopic Cardiac Calcification in Mice With Metabolic Syndrome

Autor: Yoshiro Naito, Hisashi Sawada, Seiki Yasumura, Tetsuo Horimatsu, Keisuke Okuno, Saki Tahara, Koichi Nishimura, Masanori Asakura, Takeshi Tsujino, Tohru Masuyama, Masaharu Ishihara
Rok vydání: 2022
Předmět:
Zdroj: Circulation: Heart Failure. 15
ISSN: 1941-3297
1941-3289
DOI: 10.1161/circheartfailure.121.009034
Popis: 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.
Databáze: OpenAIRE