Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure

Hyun-Ji Park; John M. Kelly; Jessica R. Hoffman; Felipe Takaesu; William Schwartzman; Anudari Ulziibayar; Takahiro Kitsuka; Eric Heuer; Asigul Yimit; Raphael Malbrue; Cole Anderson; Adrienne Morrison; Aymen Naguib; Christopher Mckee; Andrew Harrison; Brian Boe; Aimee Armstrong; Arash Salavitabar; Andrew Yates; Toshiharu Shinoka; Sergio Carrillo; Christopher K. Breuer; Michael E. Davis

Extracellular Vesicle (Dec 2022)

Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure

Hyun-Ji Park,
John M. Kelly,
Jessica R. Hoffman,
Felipe Takaesu,
William Schwartzman,
Anudari Ulziibayar,
Takahiro Kitsuka,
Eric Heuer,
Asigul Yimit,
Raphael Malbrue,
Cole Anderson,
Adrienne Morrison,
Aymen Naguib,
Christopher Mckee,
Andrew Harrison,
Brian Boe,
Aimee Armstrong,
Arash Salavitabar,
Andrew Yates,
Toshiharu Shinoka,
Sergio Carrillo,
Christopher K. Breuer,
Michael E. Davis

Affiliations

Hyun-Ji Park: Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine & Georgia Institute of Technology, Atlanta, GA, USA; Department of Molecular Science and Technology, Ajou University, Republic of Korea
John M. Kelly: Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA; The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
Jessica R. Hoffman: Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine & Georgia Institute of Technology, Atlanta, GA, USA; Molecular & Systems Pharmacology Graduate Training Program, Graduate Division of Biological & Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA
Felipe Takaesu: Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine & Georgia Institute of Technology, Atlanta, GA, USA
William Schwartzman: The Ohio State University College of Medicine, Columbus, OH, USA
Anudari Ulziibayar: Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
Takahiro Kitsuka: Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
Eric Heuer: Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
Asigul Yimit: Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
Raphael Malbrue: The Ohio State University College of Veterinary Medicine, Columbus, OH, USA
Cole Anderson: Biomedical Engineering Graduate Program, The Ohio State University, Columbus, OH, USA
Adrienne Morrison: Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
Aymen Naguib: The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
Christopher Mckee: The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
Andrew Harrison: The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA
Brian Boe: The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
Aimee Armstrong: The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
Arash Salavitabar: The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
Andrew Yates: The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
Toshiharu Shinoka: Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA; The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Surgery, Nationwide Children’s Hospital, Columbus, OH, USA
Sergio Carrillo: The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Surgery, Nationwide Children’s Hospital, Columbus, OH, USA
Christopher K. Breuer: Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Surgery, Nationwide Children’s Hospital, Columbus, OH, USA; Corresponding author at: Department of Surgery, Nationwide Children’s Hospital, Columbus, OH, USA.
Michael E. Davis: Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine & Georgia Institute of Technology, Atlanta, GA, USA; Molecular & Systems Pharmacology Graduate Training Program, Graduate Division of Biological & Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA; Children’s Heart Research & Outcomes (HeRO) Center, Children’s Healthcare of Atlanta & Emory University, Atlanta, GA, USA; Corresponding author at: Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine & Georgia Institute of Technology, Atlanta, GA, USA.

Journal volume & issue: Vol. 1
p. 100013

Abstract

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Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

Published in Extracellular Vesicle

ISSN: 2773-0417 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Biology (General); Medicine: Medicine (General)
Website: https://www.sciencedirect.com/journal/extracellular-vesicle

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