Heart failure & cardiomyopathies
Sam68 Exacerbates Pathologic Cardiac Hypertrophy by Suppressing Cardiomyocyte Glucose Oxidation
Authors' conclusion
Sam68 is a stress-activated cardiomyocyte scaffold that drives pathologic hypertrophy through a Src-STAT3-PDK4 program that inhibits PDH and suppresses glucose oxidation.
Study context
- Population
- Mouse TAC and angiotensin II hypertrophy models; failing human hearts
- Comparison
- Sam68cKO vs Sam68 overexpression (Sam68OE)
Main finding
As reported in the abstract
- Sam68 increased in failing human cardiomyocytes and murine hypertrophic hearts
- Sam68cKO markedly attenuated angiotensin II- and TAC-induced hypertrophy; Sam68OE aggravated remodeling and dysfunction
- TAC uncoupled glycolysis from glucose oxidation (reduced 13C entry into TCA cycle) at 3 days and 4 weeks; Sam68 deletion restored glucose-derived carbon entry into TCA cycle and PDH-dependent M+2 labeling
- Sam68 promoted Src-dependent STAT3 Tyr705 phosphorylation and PDK4 induction, leading to PDH Ser293 phosphorylation and suppressed PDH activity
- PDK4 inhibitor blunted Sam68OE-driven remodeling, preserving PDH activity
- YB-0158 disrupted Sam68-Src engagement in vivo and improved TAC remodeling; effects lost in Sam68cKO mice
- In failing human hearts SAM68 increased in parallel with PDK4 and reduced LVEF
Original publication
Sam68 Exacerbates Pathologic Cardiac Hypertrophy by Suppressing Cardiomyocyte Glucose Oxidation. Circulation. Published 22 May 2026. doi:10.
Summarised from the published abstract; every number is checked against it