AI Article Synopsis
- Research showed that DNA methylation profiles in pig heart tissue can change after a lack of blood supply (ischemia) and treatment with extracellular vesicles (EV) in different diet conditions.
- The study involved four groups of pigs, comparing those on a normal diet and a high-fat diet, with some receiving EV injections and others receiving saline.
- Numerous loci with notable differences in methylation were identified between ischemic and normal tissues, indicating that while there are significant changes in DNA methylation, the overall effects are modest.
Article Abstract
Introduction: Research has shown epigenetic change via alternation of the methylation profile of human skeletal muscle DNA after Cardio-Pulmonary Bypass (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 . 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 value < 0.05 when examining the effect of ischemia . normal heart tissue on a normal diet in the absence of treatment. 426 loci at value threshold < 0.05 were identified when comparing the ischemic . normal tissue from high-fat diet animals. When examining the effect of EV treatment in ischemic tissue in subjects on a normal diet, there were 574 loci with nominal value < 0.05 with two loci Fructosamine 3 kinase related protein [(FN3KRP) ( < 0.001)] and SNTG1 ( = 0.03) significant after Bonferroni correction. When examining the effect of EV treatment in ischemic tissue in HFD, there were 511 loci with nominal values < 0.05. After Bonferroni correction, two loci had values less than 0.05, betacellulin [(BTC) ( = 0.008)] and [proprotein convertase subtilisin/kexin type 7 (PCSK7) ( = 0.01)].
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656099 | PMC |
| http://dx.doi.org/10.20517/2574-1209.2023.103 | DOI Listing |
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