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• W4386822939 abstract "Abstract Systemic iron deficiency (SID), even in the absence of anaemia, worsens the prognosis and increases mortality in heart failure (HF). Recent clinical–epidemiological studies, however, have shown that a myocardial iron deficiency (MID) is frequently present in cases of severe HF, even in the absence of SID and without anaemia. In addition, experimental studies have shown a poor correlation between the state of systemic and myocardial iron. MID in animal models lead to severe mitochondrial dysfunction, alterations of mitophagy, and mitochondrial biogenesis, with profound alterations in cardiac mechanics and the occurrence of a fatal cardiomyopathy, all effects prevented by intravenous administration of iron. This shifts the focus to the myocardial state of iron, in the absence of anaemia, as an important factor in prognostic worsening and mortality in HF. There is now epidemiological evidence that SID worsens prognosis and mortality also in patients with acute and chronic coronary heart disease and experimental evidence that MID aggravates acute myocardial ischaemia as well as post-ischaemic remodelling. Intravenous administration of ferric carboxymaltose (FCM) or ferric dextrane improves post-ischaemic adverse remodelling. We here review such evidence, propose that MID worsens ischaemia/reperfusion injury, and discuss possible molecular mechanisms, such as chronic hyperactivation of HIF1-α, exacerbation of cytosolic and mitochondrial calcium overload, amplified increase of mitochondrial [NADH]/[NAD+] ratio, and depletion of energy status and NAD+ content with inhibition of sirtuin 1–3 activity. Such evidence now portrays iron metabolism as a core factor not only in HF but also in myocardial ischaemia." @default.
• W4386822939 created "2023-09-19" @default.
• W4386822939 creator A5012696157 @default.
• W4386822939 creator A5016965595 @default.
• W4386822939 creator A5032724141 @default.
• W4386822939 creator A5067302152 @default.
• W4386822939 date "2023-09-19" @default.
• W4386822939 modified "2023-10-03" @default.
• W4386822939 title "Iron deficiency in myocardial ischemia: molecular mechanisms and therapeutic perspectives" @default.
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