FGF13 Regulates Myocardial Ischemia-Reperfusion Injury via PGRN Glycosylation.

FGF13 upregulation in mouse cardiomyocytes after myocardial ischemia-reperfusion is linked to worse I/R injury, and cardiomyocyte-specific FGF13 loss alleviates dysfunction.

• Why it matters: Macrophage polarization and complement activation are central to myocardial I/R damage, but how FGF13 shapes these immune processes was unclear.
• What they did: The study used cardiomyocyte-specific FGF13 knockout and AAV9-mediated FGF13 overexpression in mice, plus transcriptomic/proteomic work and glycoproteomics to show FGF13 blocks PGRN glycosylation at asparagine 263 via competitive occupancy of asparagine 121.
• The result: Restoring PGRN glycosylation and secretion after FGF13 depletion activated macrophage TNFR2/PI3K/AKT signaling, promoted M2 polarization, suppressed M1 polarization, and reduced complement activation; the FGF13 inhibitor CWD8 attenuated myocardial I/R injury.

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