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

• Published in: Frontiers in Cardiovascular Medicine
• Main Authors: Givre, Lucas, Crola da Silva, Claire, Swenson, Jon, E, Arnemo, Jon, M, Gauquelin-Koch, Guillemette, Bertile, Fabrice, Lefai, Etienne, Gomez, Ludovic
• Other Authors: Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Norwegian University of Life Sciences (NMBU), Inland Norway University of Applied Sciences - Høgskolen i Innlandet, Swedish University of Agricultural Sciences = Sveriges lantbruksuniversitet (SLU), Centre National d’Études Spatiales Paris (CNES), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), ANR-16-CE17-0020,CARDIOCARE,Rôle des interactions mitochondrie-réticulum sarcoplasmique pendant l'infarctus du myocarde et la cardioprotection : inhibition de la GSK3ß comme potentielle thérapeutique(2016)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2021
• Subjects: cardiomyocyte; hypoxia-reoxygenation injury; protection; bear serum; hibernation; novel therapeutic strategy; [SDV]Life Sciences [q-bio]; Ursus arctos
• Online Access: https://hal.science/hal-03419383; https://hal.science/hal-03419383/document; https://hal.science/hal-03419383/file/fcvm-08-687501.pdf; https://doi.org/10.3389/fcvm.2021.687501

International audience 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.