Changes in cardiac myosin acetylation disrupt the super-relaxed state in genotype-negative hypertrophic cardiomyopathy with type 2 diabetes
Authors' conclusion
Disruption of myosin super-relaxation emerges as a central cellular defect in G-T2D HCM myocardium and can be mechanistically linked to site-specific myosin hyperacetylation at K847, providing a potential therapeutic target for genotype-negative HCM with T2D.
Study context
- Population
- Genotype-negative hypertrophic cardiomyopathy (HCM) patients; left ventricular septal myectomy samples
- Participants
- 15 vs 19
- Comparison
- Genotype-negative HCM with T2D vs without T2D
- G-T2Dn = 15
- G-n = 19reference
- Outcome
- Myosin super-relaxed state, structure and acetylation
Main finding
As reported in the abstract
- Lower fraction of myosin heads in super-relaxed (SRX) state in G-T2D vs non-diabetic myocardium (Mant-ATP chase)
- X-ray diffraction: trends toward structural alterations in myosin organization in G-T2D, consistent with altered OFF/ON state equilibrium
- Hyperacetylation of several myosin lysine residues in G-T2D, including K847 in the S2 region
- Molecular dynamics: K847 acetylation disrupts stabilizing electrostatic interactions in the interacting-heads motif (associated with OFF state)
Original publication
Changes in cardiac myosin acetylation disrupt the super-relaxed state in genotype-negative hypertrophic cardiomyopathy with type 2 diabetes. Cardiovasc Diabetol. Published 26 May 2026. doi:10.
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