FNDC5/irisin mitigates the cardiotoxic impacts of cancer chemotherapeutics by modulating ROS-dependent and -independent mechanisms.

ABSTRACT: Cardiotoxicity remains a major limiting factor in the clinical implementation of anthracycline chemotherapy. Though the etiology of doxorubicin-dependent heart damage has yet to be fully elucidated, the ability of doxorubicin to damage DNA and trigger oxidative stress have been heavily implicated in the pathogenesis of chemotherapy-associated cardiomyopathy. Here, we demonstrate that fibronectin type III domain-containing protein 5 (FNDC5), the precursor protein for myokine irisin, is depleted in the hearts of human cancer patients or mice exposed to chemotherapeutics. In cardiomyocytes, restoration of FNDC5 expression was sufficient to mitigate reactive oxygen species (ROS) accumulation and apoptosis following doxorubicin exposure, effects dependent on the irisin encoding domain of FNDC5

SUBMITTER: Kumar M 

PROVIDER: S-EPMC11850786 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature