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Broadwin et al. Vessel Plus 2023;7:25 Vessel Plus
DOI: 10.20517/2574-1209.2023.103

Original Article Open Access

Extracellular vesicle treatment partially reverts

epigenetic alterations in chronically ischemic
porcine myocardium

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Mark Broadwin 1 , Ghazal Aghagoli , Sharif A. Sabe , Dwight D. Harris , Joselynn Wallace , Jordan
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Lawson , Ashok Ragayendran , Alexey V. Fedulov , Frank W. Sellke 1
1
Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert
Medical School of Brown University, Rhode Island Hospital, Providence, RI 02909, USA.
2
Center for Computation and Visualization, Brown University, Providence, RI 02912, USA.
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Center for Computational Biology of Human Disease, Brown University, Providence, RI 02912, USA.
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Division of Surgical Research, Department of Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode
Island Hospital, Providence, RI 02909, USA.
Correspondence to: Prof. Frank W. Sellke, MD, Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular
Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI
02905, USA. E-mail: fsellke@lifespan.org
How to cite this article: Broadwin M, Aghagoli G, Sabe SA, Harris DD, Wallace J, Lawson J, Ragayendran A, Fedulov AV, Sellke
FW. Extracellular vesicle treatment partially reverts epigenetic alterations in chronically ischemic porcine myocardium. Vessel
Plus 2023;7:25. https://dx.doi.org/10.20517/2574-1209.2023.103
Received: 8 Aug 2023 First Decision: 26 Sep 2023 Revised: 12 Oct 2023 Accepted: 27 Oct 2023 Published: 3 Nov 2023
Academic Editor: Narasimham L. Parinandi Copy Editor: Fangling Lan Production Editor: Fangling Lan

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 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 < 0.05 when examining the effect of ischemia vs.
normal heart tissue on a normal diet in the absence of treatment. 426 loci at P value threshold < 0.05 were
identified when comparing the ischemic vs. normal tissue from high-fat diet animals. When examining the effect of

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
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