Epigenetic alterations in chronically ischemic porcine myocardium

Introduction: Research has shown epigenetic change via alternation of the methylation profile of human skeletal muscle DNA after CPB. In this study we investigated the change in epigenome-wide DNA methylation profiles of porcine myocardium after ischemic insult in the setting of treatment with extracellular vesicle (EV) therapy in normal vs high-fat diet (HFD) pigs.Methods: Four groups of three pigs underwent ameroid constrictor placement to the left circumflex artery (LCx) and were assigned to the following groups: (1) normal diet saline injection, (2) normal diet EV injection, (3) HFD saline injection, and (4) HFD EV injection. DNA methylation was profiled via reduced-representation bisulfite sequencing (RRBS) and compared using a custom bioinformatic pipeline.Results:After initial analysis 441 loci had a nominal p value Conclusions: Alterations in DNA methylation were identified in pig myocardium after ischemic insult, change in diet, and treatment with EVs. Hundreds of differentially methylated loci were detected, but the magnitude of the effects was low. These changes represent significant alterations in DNA methylation and merit further investigation.