Sam68 Exacerbates Pathologic Cardiac Hypertrophy by Suppressing Cardiomyocyte Glucose Oxidation - PubMed
3 hours ago
- #cardiac hypertrophy
- #glucose oxidation
- #Sam68
- Sam68 is elevated in failing human hearts and hypertrophic murine models.
- Sam68 promotes pathologic cardiac hypertrophy by suppressing glucose oxidation via the Src-STAT3-PDK4 pathway.
- Genetic knockout of Sam68 attenuates hypertrophy and restores glucose-derived carbon entry into the TCA cycle.
- Overexpression of Sam68 worsens remodeling and dysfunction in pressure overload models.
- Sam68 acts as a stress-activated scaffold, enhancing Src-dependent STAT3 phosphorylation and PDK4 transcription.
- PDK4 inhibition or disruption of Sam68-Src interaction mitigates hypertrophy and preserves PDH activity.
- The Sam68-Src-STAT3-PDK4 axis is activated in human heart failure, correlating with reduced ejection fraction.
- Targeting Sam68 restores PDH-dependent pyruvate oxidation and limits pathological remodeling.