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Release of Mitochondrial and Nuclear DNA During On-Pump Heart Surgery: Kinetics and Relation to Extracellular Vesicles

  • Anton Baysa
  • Anton Fedorov
  • Kirill Kondratov
  • Arno Ruusalepp
  • Sarkis Minasian
  • Michael Galagudza
  • Maxim Popov
  • Dmitry Kurapeev
  • Alexey Yakovlev
  • Guro Valen
  • Anna Kostareva
  • Jarle Vaage
  • Kåre-Olav StensløkkenEmail author
Original Article
  • 60 Downloads

Abstract

During heart surgery with cardiopulmonary bypass (CPB), the release of mitochondrial (mtDNA) and nuclear DNA (nDNA) and their association to extracellular vesicles were investigated. In patients undergoing elective coronary artery bypass grafting (CABG, n = 12), blood was sampled before, during, and after surgery from peripheral artery, pulmonary artery, and the coronary sinus. Plasma was separated in three fractions: microvesicles, exosomes, and supernatant. mtDNA and nDNA were measured by qPCR. mtDNA and nDNA levels increased after start of surgery, but before CPB, and increased further during CPB. mtDNA copy number was about 1000-fold higher than nDNA. mtDNA was predominantly localized to the vesicular fractions in plasma, whereas nDNA was predominantly in the supernatant. The amount of free mtDNA increased after surgery. There was no net release or disappearance of DNAs across the pulmonary, systemic, or coronary circulation. Extracellular DNAs, in particular mtDNA, may be important contributors to the whole-body inflammation during CPB.

Keywords

Extracellular DNA Cardiac surgery Exosomes Microvesicles 

Notes

Acknowledgements

We gratefully acknowledge Torun Flatebø for technical support with qPCR and Maksim Puzanov for assistance in sample collection. Low-voltage scanning electron microscopy was performed using equipment of the Interdisciplinary Resource Center for Nanotechnology of Saint Petersburg State University.

Funding

This study was funded by the Norwegian Research Council (#214557), Gjensidige stiftelsen, Anders Jahres fund, Russian Science Foundation (#17-75-30052), and the University of Oslo.

Compliance with Ethical Standards

The studies were performed in agreement with the ethical standards stated in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The studies were approved by the Regional Ethics Committee in Oslo, Norway; Tartu University Hospital, Estonia; or the Institutional Ethics Committee at Almazov National Medical Research Centre, Saint Petersburg, Russia. Written, informed consent was obtained from all patients.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12265_2018_9848_MOESM1_ESM.docx (16 kb)
ESM 1 (DOCX 15 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Anton Baysa
    • 1
    • 2
  • Anton Fedorov
    • 3
    • 4
  • Kirill Kondratov
    • 3
  • Arno Ruusalepp
    • 5
  • Sarkis Minasian
    • 3
  • Michael Galagudza
    • 3
  • Maxim Popov
    • 3
  • Dmitry Kurapeev
    • 3
  • Alexey Yakovlev
    • 3
  • Guro Valen
    • 1
    • 2
  • Anna Kostareva
    • 3
  • Jarle Vaage
    • 6
  • Kåre-Olav Stensløkken
    • 1
    • 2
    Email author
  1. 1.Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical ScienceUniversity of OsloOsloNorway
  2. 2.Center for Heart Failure ResearchUniversity of OsloOsloNorway
  3. 3.Almazov National Medical Research CentreSaint PetersburgRussia
  4. 4.Department of Cytology and HistologySaint Petersburg State UniversitySaint PetersburgRussia
  5. 5.Department of Cardiac SurgeryTartu University HospitalTartuEstonia
  6. 6.Institute of Clinical Medicine, Oslo University HospitalUniversity of OsloOsloNorway

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