Heart failure & cardiomyopathies
S-Nitrosylation of Pyruvate Kinase Isoform 2 Drives Cardiac Fibrosis by Promoting Mitochondrial Fission
Authors' conclusion
SNO-PKM2 specifically increases in cardiac fibroblasts and activated cardiac fibroblasts by inducing excessive mitochondrial fission through a gelsolin-dependent manner.
Study context
- Population
- HF patients' heart tissue, murine cardiac fibrosis models (TAC mice, spontaneously hypertensive rats) and cardiac fibroblasts
Main finding
As reported in the abstract
- S-nitrosylation (SNO) of pyruvate kinase M2 (PKM2) at cysteine 49 and 326 increased in HF patients' heart tissue, murine cardiac fibrosis models and angiotensin II-stimulated cardiac fibroblasts
- SNO of PKM2 (SNO-PKM2) reduced pyruvate kinase activity and PKM2 tetramerization
- Cardiac fibroblast-specific PKM2 knockout aggravated cardiac fibrosis; knockout mice transfected with SNO-resistant mutant rather than wild-type PKM2 had cardiac function
- SNO-PKM2 drove excessive mitochondrial fission and dysfunction by interfering with its interaction with gelsolin
- TEPP-46 (PKM2 activator) alleviated mitochondrial fission and cardiac fibrosis
- Mitapivat showed preventive and therapeutic effects on cardiac fibrosis through activating PKM2
Original publication
S-Nitrosylation of Pyruvate Kinase Isoform 2 Drives Cardiac Fibrosis by Promoting Mitochondrial Fission. Circulation. Published 10 December 2025. doi:10.
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