Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Navigation/Suche
- Forscher*innen
- Institutionen
- Projekte
- Publikationen
- Partner
- Geldgeber
- Ausstattung
- Knowhow
- Forschungsfelder
"Köpfe" der aktuellen Meldungen:
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Degezelle, MM; Chaami, C; Lewis, CTA; Zhang, C; Hessel, AL; Rainer, PP; Kirk, JA; Stokke, MK; Seaborne, RAE; Ochala, J.
Destabilization of cardiac myosin acetylation and sequestration with type 2 diabetes mellitus.
Cardiovasc Diabetol. 2026;
Doi: 10.1186/s12933-025-03052-5
PubMed
FullText
FullText_MUG
- Autor*innen der Med Uni Graz:
- Rainer Peter
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- BACKGROUND: Type 2 diabetes mellitus (T2DM) predisposes patients to adverse cardiac remodeling even before the development of cardiomyopathic symptoms. The mechanisms for such early perturbations remain elusive. Given that myosin is the most abundant and energy‑demanding cardiac protein, we tested whether its regulation is impaired even in non‑failing human diabetic hearts. METHODS: Left ventricular strips were individually isolated from organ donors with and without T2DM. These strips were then subjected to a combination of acetyl‑proteomics, X-ray diffraction, in-silico simulations and Mant-ATP chase experiments. RESULTS: Strikingly, we identified nine cardiac myosin (MYH7) lysine residues with significantly altered acetylation levels in T2DM ventricles, many of which were predicted to destabilize the protein coiled‑coil regions. Consistently, X‑ray diffraction revealed increased lattice spacing and a shift towards myosin ON‑state in T2DM tissue. However, and surprisingly, Mant‑ATP chase analyses indicated no bioenergetic consequences at the myosin level. CONCLUSIONS: Human T2DM myocardium exhibits early, site‑specific myosin acetylations that destabilize myosin structural OFF‑state. This myosin 'preload' remodeling occurs at no energetic cost and may constitute a potential early marker of latent myocardial vulnerability in T2DM.