L’inhibition de PDZRN3 est requise pour la maturation cardiomyocytaire post-natal et protège de l’insuffisance cardiaque

Abstract : During heart maturation, individual cardiomyocytes stretch out and connect some with the others via their extremities by intercalated disk protein complexes. This planar and directionnel organization of the myocyte sis crucial for the machanical coupling and the anisotropic conduction of the electric signal in the heart. One of the hallmarks of heart failure concerns alterations in the contact sites between cardiomyocytes. Yet no factors on its own is known to coordinate cardiomyocyte polarized organization. Here we reported enhanced levels of Pdzrn3 in the diseased hypertrophic human and mouse myocardium, correlated with the loss of cardiomyocyte polarized elongation. Furthermore, mouse cardiac Pdzrn3 deficiency protected against heart failure in a mouse model of hypertrophic cardiomyopathy. Our results reveal a novel signaling that controls a genetic program essential for heart maturation and for maintain of cardiomyocyte overall geometry and contractile function and implicates PDZRN3 as a potential therapeutic target for human heart failure protection.
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Mathieu Pernot. L’inhibition de PDZRN3 est requise pour la maturation cardiomyocytaire post-natal et protège de l’insuffisance cardiaque. Médecine humaine et pathologie. Université de Bordeaux, 2017. Français. ⟨NNT : 2017BORD0841⟩. ⟨tel-02183844⟩

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