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

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.

Blood transcriptomics mirror regulatory mechanisms during hibernation—a comparative analysis of the Djungarian hamster with other mammalian species

“…In non-hibernators, an extensive drop in T b would lead to cardiac arrhythmias, which can result in heart infarction, sudden cardiac death, or causes ischemic reperfusion (IR) injury upon arousal [ 68 ]. Adapted signalling pathways enable the regulation of ion transporters, which control cardiac contraction and relaxation, and the elevated production of anti-oxidative enzymes, which protect from cardiac injury during and after torpor/hibernation together with an upregulation of anti-apoptotic genes [ 30 , 68 ]. Kidney adaptations likewise permit to withstand low T b and organ perfusion as well as reperfusion by the increase of antioxidant enzymes and the downregulation of pro-apoptotic processes [ 40 ].…”