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Etude cellulaire et moléculaire de l'insuffisance cardiaque à fonction systolique préservée

Abstract : Heart failure with preserved ejection fraction (HFpEF) is a growing health problem. It could become the leading cause of HF within a decade. It is a pathology associated with high morbidity and mortality. Therapeutic options are limited due to a lack of knowledge of the pathology and its evolution. In this work, we investigated the cellular phenotype and Ca2+ handling in hearts recapitulating HFpEF criteria. HFpEF was induced in a portion of male Wistar rats four weeks after abdominal aortic banding. These animals had nearly normal ejection fraction and presented elevated blood pressure, lung congestion, concentric hypertrophy, increased LV mass, wall stiffness, impaired active relaxation and passive filling of the left ventricle, enlarged left atrium, and cardiomyocyte hypertrophy. Left ventricular cell contraction was stronger and the Ca2+ transient larger. Ca2+ cycling was modified with a RyR2 mediated Ca2+ leak from the sarcoplasmic reticulum and impaired Ca2+ extrusion through the Na+ /Ca2+ (NCX), which promoted an increase in diastolic Ca2+ and spontaneous Ca2+ waves. PLN phosphorylation which promotes SERCA2a activity, was increased, suggesting an adaptive compensation of Ca2+ cycling. In the presence of Ranolazine, a sustained sodium current inhibitor, spontaneous Ca2+ events were suppressed. Cardiac remodeling in hearts with a HFpEF status differs from that known for HFrEF and opens the way to new pathophysiological and therapeutic actors.
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Submitted on : Thursday, February 7, 2019 - 11:12:34 AM
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Sarah Rouhana. Etude cellulaire et moléculaire de l'insuffisance cardiaque à fonction systolique préservée. Sciences agricoles. Université Montpellier; Université Saint-Joseph (Beyrouth). Faculté française de médecine et de pharmacie, 2018. Français. ⟨NNT : 2018MONTT067⟩. ⟨tel-02010470⟩

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