Heart protection by ischemic preconditioning: A novel pathway initiated by iron and mediated by ferritin

2008 
Abstract Ischemic preconditioning is a well-known procedure transiently protecting the heart against injury associated with prolonged ischemia, through mechanism/s only partly understood. The aim of this study was to test whether preconditioning-induced protection of the heart involves an iron-based mechanism, including the generation of an iron signal followed by accumulation of ferritin. In isolated rat hearts perfused in the Langendorff configuration, we measured heart contractility, ferritin levels, ferritin-iron content, and mRNA levels of ferritin subunits. Ischemic preconditioning caused rapid accumulation of ferritin, reaching 359% of the baseline value (set at 100%). This was accompanied by a parallel decline in ferritin-bound iron: from 2191 ± 548 down to 760 ± 34 Fe atoms/ferritin molecule, p vs 1.23 ± 0.15 (units) in the baseline, p de novo synthesis of ferritin in the heart; the extra ferritin is proposed to serve a ‘sink’ for redox-active iron, thus protecting the heart from iron-mediated oxidative damage associated with ischemia–reperfusion injury. The present results substantiate a novel iron-based mechanism of ischemic preconditioning and could pave the way for the development of new modalities of heart protection.
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