Vascular Pharmacology
Volume 155, June 2024, 107348

Ketogenic diet improves chromatin remodeling and rescues mitochondrial dysfunction in ischemic heart disease by regulating PGC-1alpha transcription

https://doi.org/10.1016/j.vph.2024.107348

Background

The exact molecular processes underlying the progression of post-ischemic heart failure (HF) are not fully understood.

Methods

We carried out a coordinated set of in vivo and in vitro experiments using human cardiac specimens from patients with post-ischemic HF and healthy controls, a mouse model of HF, and mechanistic studies in vitro.

Results

We identified a specific pattern of maladaptive chromatin remodeling, namely a double methylation of histone 3 at lysine 27 and one methylation of lysine 36 (H3_K27me2K36me1) consistently induced by ischemic injury in all these settings: human HF, murine HF, and in vitro models. To translate our findings in vivo, we used an established murine model of HF induced by myocardial infarction, obtained by permanent ligation of the left anterior descending coronary artery. After surgery, the mice were

Conclusions

Our findings establish maladaptive chromatin remodeling as a novel mechanism in post-ischemic heart disease, functionally modulated by ketone bodies.