Anti-apoptotic peptide for long term cardioprotection in a mouse model of myocardial ischemia–reperfusion injury

Aurélie Covinhes (1, 2) , Laura Gallot (1, 2) , Christian Barrère (1, 2) , Anne Vincent (1, 2) , Catherine Sportouch (1, 2, 3) , Christophe Piot (1, 2, 3) , Bernard Lebleu (4) , Joël Nargeot (1, 2) , Prisca Boisguérin (5, 6) , Stéphanie Barrère-Lemaire (1, 2)

1 IGF - Institut de Génomique Fonctionnelle
2 LabEx Ion Channel Science and Therapeutics
3 Clinique du Millénaire - Oc Santé [Montpellier]
4 LPHI - Laboratory of Pathogen Host Interactions [Montpellier]
5 CRBM - Centre de recherche en Biologie cellulaire de Montpellier
6 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]

Reperfusion therapy during myocardial infarction (MI) 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 evidenced recently the potent cardioprotective effect of the anti-apoptotic Tat-DAXXp (TD) peptide targeting the FAS-dependent extrinsic pathway. The aim of the present study was to evaluate TD long term cardioprotective effects against IR injury in a MI mouse model. TD peptide (1 mg/kg) was administered in mice subjected to MI (TD; n = 21), 5 min prior to reperfusion, and were clinically followed-up during 6 months after surgery. 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). In conclusion, targeting the extrinsic pathway with TD peptide at the onset of reperfusion provided long-term cardioprotection in a mouse model of myocardial IR injury by improving post-MI cardiac performance and preventing cardiac remodeling.

Domaines: Sciences du Vivant [q-bio]

Aurélie Covinhes, Laura Gallot, Christian Barrère, Anne Vincent, Catherine Sportouch, et al.. Anti-apoptotic peptide for long term cardioprotection in a mouse model of myocardial ischemia–reperfusion injury. Scientific Reports, 2020, 10 (1), ⟨10.1038/s41598-020-75154-x⟩. ⟨hal-02982345⟩