Key result
Heart failure in dogs was associated with decreased Sirt-3 and NAD+ levels, increased CD38 and CyPD levels, and reduced Complex-I activity compared to normal dogs, indicating hyperacetylation.
Why the study?
Hyperacetylation of mitochondrial proteins can cause abnormalities of the electron transport chain and oxidative phosphorylation, prompting investigation into the levels of proteins that regulate acetylation in heart failure.
Does coronary microembolization-induced heart failure alter mitochondrial regulatory proteins and function in dog left ventricular myocardium?
Does coronary microembolization-induced heart failure alter mitochondrial regulatory proteins and function in dog left ventricular myocardium?
Heart failure in a canine model is associated with mitochondrial protein hyperacetylation, which may contribute to mitochondrial dysfunction.
Mitochondrial shifts in canine HF models are hypothesis-generating; leaves open therapeutic targeting in patients.
Increased acetylation or “hyperacetylation” of mitochondrial (MITO) proteins can lead to abnormalities of the electron transport chain (ETC) and oxidative phosphorylation. In this study we examined the levels of proteins that regulate acetylation. Studies were performed in isolated MITO fractions from left ventricular (LV) myocardium of seven healthy normal (NL) dogs and seven dogs with coronary microembolization-induced heart failure (HF, LV ejection fraction ~35%). Protein levels of drivers of hyperacetylation, namely sirtuin-3 (Sirt-3), a MITO deacetylase, and CD38, a regulator of nicotinamide adenine dinucleotide (NAD+), were measured by Western blotting, and the bands were quantified in densitometric units (du). To assess MITO function, MITO components directly influenced by a hyperacetylation state, namely the protein level of cytophillin-D (CyPD), a regulator of MITO permeability transition pore and MITO Complex-I activity, were also measured. Protein level of Sirt-3 and amount of NAD+ were decreased in HF compared to NL dogs. Protein levels of CD38 and CyPD were increased in HF compared to NL dogs. Complex-I activity was decreased in HF compared to NL dogs. The results support the existence of a protein hyperacetylation state in mitochondria of failing LV myocardium compared to NL. This abnormality can contribute to MITO dysfunction as evidenced by reduced Complex-I activity and opening of MITO permeability pores.
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Gupta et al. (2025) studied Chronic Heart Failure (n=14). Coronary microembolization-induced heart failure vs. Healthy normal dogs was evaluated on Protein levels of Sirt-3, CD38, CyPD, NAD+ amount, and Complex-I activity. Heart failure in dogs was associated with decreased Sirt-3 and NAD+ levels, increased CD38 and CyPD levels, and reduced Complex-I activity compared to normal dogs, indicating hyperacetylation.
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