Cardiac ferroptosis: new jigsaw in SCD puzzles

In this issue of Blood, Menon et al(1) demonstrate that excess circulating heme and reduced hemopexin in a murine model of sickle cell disease (SCD) led to excess non-hemopexin-bound heme (free heme). This free heme can enter cardiac cells and, thereby, upregulate the expression of the heme oxygenase 1 (HMOX1), resulting in an increased level of ferrous ion (Fe2+) in cardiac cells. This cardiac Fe2+ overload was found to promote cardiomyocyte ferroptosis, a specific type of regulated cell death, potentially leading to impaired cardiac contractility. These findings revealed important mechanisms underlying cardiac complications in SCD, which enhance our previously limited knowledge of cardiac dysfunction and provide the potential for novel interventional approaches for cardioprotection in patients with SCD.

Automated summary

Excess free heme and reduced hemopexin in sickle cell disease can lead to the overload of ferrous ion in cardiac cells, promoting cardiomyocyte ferroptosis and potentially impairing cardiac contractility.