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TD peptide as an adjunct of reperfusion therapy provides long-term cardioprotective effects in a mouse model of ischemia-reperfusion

Abstract : Introduction: During myocardial infarction (MI), reperfusion therapy leads to side effects called ischemia-reperfusion (IR) injury for which no treatment exists. While most studies have targeted the intrinsic apoptotic pathway to prevent IR injury with no successful clinical translation, we have developed a cardioprotective tool, the anti-apoptotic Tat-DAXXp (TD) peptide, targeting the FAS-dependent extrinsic pathway and recently evidenced as a potent therapeutic molecule.Objective: The aim of the present study was to evaluate TD long term cardioprotective effects in a mouse model of reperfused infarction.Methods: TD peptide was evaluated in a mouse model of myocardial infarction (40 minutes ischemia) followed by reperfusion and 6 month-follow up. TD peptide (1 mg/kg) was administered in mice subjected to MI (TD; n=21), 5 min prior to reperfusion. Cardiac injury in the study cohort was assessed by the quantification of cardiac Troponin I levels at 24h post-MI and each month of the period. Preclinical evaluation was performed by the mean of echocardiographic follow-up using both conventional and strain parameters. An histological analysis was performed at the end of the protocol for the quantification of fibrosis extend.Results Plasma cTnI concentration evaluated 24 h post-MI was 70%-decreased in TD (n=16) versus Ctrl (n=20) mice (p***). Strain echocardiography highlighted a 24%-increase (p****) in the ejection fraction mean value in TD-treated (n=12) versus Ctrl mice (n=17) during the 6 month-period. Improved cardiac performance was associated to a 54%-decrease (p**) in left ventricular fibrosis at 6 months in TD (n=16) versus Ctrl (n=20).Conclusion:Targeting the extrinsic pathway with the TD peptide at the onset of reperfusion provided long term cardioprotection in a mouse model of myocardial reperfused infarction by improving post-MI cardiac performance and preventing cardiac remodeling.
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Contributeur : Stephanie Barrere-Lemaire Connectez-vous pour contacter le contributeur
Soumis le : mardi 16 novembre 2021 - 00:06:07
Dernière modification le : jeudi 26 mai 2022 - 03:50:55

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Stéphanie Barrère-Lemaire, Aurélie Covinhes, Laura Gallot, Christian Barrère, Anne Vincent, et al.. TD peptide as an adjunct of reperfusion therapy provides long-term cardioprotective effects in a mouse model of ischemia-reperfusion. e-Printemps de la Cardiologie 2021, May 2021, econgres, France. 13 (2), pp.202, 2021, ⟨10.1016/j.acvdsp.2021.04.133⟩. ⟨hal-03429860⟩



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