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Research article - Peer-reviewed, 2021

Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction

Givre, Lucas; Da Silva, Claire Crola; Swenson, Jon E.; Arnemo, Jon M.; Gauquelin-Koch, Guillemette; Bertile, Fabrice; Lefai, Etienne; Gomez, Ludovic

Abstract

Ischemic heart disease remains one of the leading causes of death worldwide. Despite intensive research on the treatment of acute myocardial infarction, no effective therapy has shown clinical success. Therefore, novel therapeutic strategies are required to protect the heart from reperfusion injury. Interestingly, despite physical inactivity during hibernation, brown bears (Ursus arctos) cope with cardiovascular physiological conditions that would be detrimental to humans. We hypothesized that bear serum might contain circulating factors that could provide protection against cell injury. In this study, we sought to determine whether addition of bear serum might improve cardiomyocyte survival following hypoxia-reoxygenation. Isolated mouse cardiomyocytes underwent 45 min of hypoxia followed by reoxygenation. At the onset of reoxygenation, cells received fetal bovine serum (FBS; positive control), summer (SBS) or winter bear serum (WBS), or adult serums of other species, as indicated. After 2 h of reoxygenation, propidium iodide staining was used to evaluate cell viability by flow cytometry. Whereas, 0.5% SBS tended to decrease reperfusion injury, 0.5% WBS significantly reduced cell death, averaging 74.04 +/- 7.06% vs. 79.20 +/- 6.53% in the FBS group. This cardioprotective effect was lost at 0.1%, became toxic above 5%, and was specific to the bear. Our results showed that bear serum exerts a therapeutic effect with an efficacy threshold, an optimal dose, and a toxic effect on cardiomyocyte viability after hypoxia-reoxygenation. Therefore, the bear serum may be a potential source for identifying new therapeutic molecules to fight against myocardial reperfusion injury and cell death in general.

Keywords

cardiomyocyte; hypoxia-reoxygenation injury; protection; bear serum; hibernation; novel therapeutic strategy

Published in

Frontiers in Cardiovascular Medicine
2021, volume: 8, article number: 687501
Publisher: FRONTIERS MEDIA SA

Authors' information

Givre, Lucas
Universite Claude Bernard Lyon 1
Da Silva, Claire Crola
Universite Claude Bernard Lyon 1
Swenson, Jon E.
Norwegian University of Life Sciences
Inland Norway University of Applied Sciences
Swedish University of Agricultural Sciences, Department of Wildlife, Fish and Environmental Studies
Gauquelin-Koch, Guillemette
Ctr Natl Etud Spatiales
Bertile, Fabrice
Universites de Strasbourg Etablissements Associes
Lefai, Etienne
Universite Clermont Auvergne (UCA)
Gomez, Ludovic
Universite Claude Bernard Lyon 1

UKÄ Subject classification

Clinical Science

Publication Identifiers

DOI: https://doi.org/10.3389/fcvm.2021.687501

URI (permanent link to this page)

https://res.slu.se/id/publ/113278