PPARβ/δ preconditioning increased the cardioprotective effects of MSC in IR injury - Université de Montpellier Accéder directement au contenu
Proceedings/Recueil Des Communications Année : 2022

PPARβ/δ preconditioning increased the cardioprotective effects of MSC in IR injury

Résumé

Introduction: Mesenchymal Stromal/Stem Cells (MSC) have been widely used for their therapeutic properties in acute myocardial infarction (AMI) due to their pleiotropic anti-inflammatory, anti-apoptotic, anti-fibrotic and pro-angiogenic properties. Despite promising results in animal studies and their safety/efficacy in phase I/II trials, inconsistencies have been reported in phase III. We have recently shown in a mouse model of ischemia-reperfusion (IR) that the cardioprotective effect of MSC administered during reperfusion was dependent on the presence of PPARβ/δ receptors. However, the role of the modulation of PPARβ/δ on MSC anti-apoptotic and cardioprotective properties has never been investigated. Objectives: this study aims investigating the role of PPARβ/δ activation on MSC therapeutic properties in an ex vivo model of AMI and their anti-apoptotic functions on cardiac cells.Method: isolated mouse hearts were subjected to 30 minutes of global ischemia and 60 minutes of reperfusion (IR). Murine MSC (naïve MSC), MSCago (pretreated with GW0742 1 µM agonist) MSCantago (pretreated with GSK0660 1µM) were administered in the perfusion system during the reperfusion period. Specific DNA fragmentation was quantified in MSC or MSCago challenged with 350 µM H2O2 during 4 hours and in H9c2 rat cardiomyoblasts and EAhy926 human endothelial cells challenged with H2O2 and co-cultured with naïve or primed MSC.Results: MSCago injection during reperfusion decreased infarct size by a larger extent than MSC, an effect lost with MSCantago. Accordingly, an increased number of cells of MSCago was detected in the left ventricular wall after 1 hour of reperfusion. In vitro, we observed for MSCago an increased resistance against oxidative resistance and a more potent anti-apoptotic effect on both cardiomyocytes and endothelial cells in vitro than naive MSC.Conclusion: MSC preconditioning via PPARβ/δ enhanced their cardioprotective effect against IR injury ex vivo by both increasing their resistance to oxidative stress and their anti-apoptotic effects on myocytes and endothelial cells. These results could be of major interest to improve MSC efficacy for the cardioprotection of the myocardium in AMI patients.

Dates et versions

hal-03852220 , version 1 (14-11-2022)

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Rafael Contreras-Lopez, Charlotte Sarre, Nitirut Nerpermpisooth, Anne Vincent, Joel Nargeot, et al.. PPARβ/δ preconditioning increased the cardioprotective effects of MSC in IR injury. 14 (2), pp.174-175, 2022, ⟨10.1016/j.acvdsp.2022.04.044⟩. ⟨hal-03852220⟩
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