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Leveraging FHF modulation to inhibit arrhythmogenic late sodium current

Nature Cardiovascular Research volume 1, pages 548–549 (2022)Cite this article

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Fibroblast growth factor homologous factors (FHFs) are an auxiliary subunit of the cardiac voltage-gated sodium channel. We found that FHFs can inhibit the arrhythmogenic late sodium current (INa,L) in an isoform-specific manner, and engineered an FHF-based cell-penetrating peptide that acts as an inhibitor of INa,L and opens avenues for developing future therapeutics.

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Fig. 1: FHFs as potent INa,L inhibitors.

References

  1. Remme, C. A., Wilde, A. A. M. & Bezzina, C. R. Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations. Trends Cardiovasc. Med. 18, 78–87 (2008). A review article that summaries variable clinical manifestations of cardiac NaV1.5 channelopathies.

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  2. Horvath, B. & Bers, D. The late sodium current in heart failure: pathophysiology and clinical relevance. ESC Heart Fail. 1, 26–40 (2014). A review article that presents recent advances in understanding of the role of INa,L in cardiac pathophysiology.

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  3. Abrams, J. M. et al. Fibroblast growth factor homologous factors tune arrhythmogenic late NaV1.5 current in calmodulin-binding-deficient channels. JCI Insight 5, e141736 (2020). A paper that shows that FHF inhibits INa,L.

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This is a summary of: Chakouri, N. et al. Fibroblast growth factor homologous factors serve as a molecular rheostat in tuning arrhythmogenic cardiac late sodium current. Nat. Cardiovasc. Res. https://doi.org/10.1038/s44161-022-00060-6 (2022).

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Leveraging FHF modulation to inhibit arrhythmogenic late sodium current. Nat Cardiovasc Res 1, 548–549 (2022). https://doi.org/10.1038/s44161-022-00077-x

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