Early calcium handling imbalance in pressure overload-induced heart failure with nearly normal left ventricular ejection fraction

Autor: Amanda Finan, Jérôme Roy, Olivier Cazorla, Nassim Fares, Cyril Reboul, Sarah Rouhana, Franck Aimond, Jérôme Thireau, Glaucy Rodrigues de Araújo, Valérie Scheuermann, Charlotte Farah, Patrice Bideaux, Youakim Saliba, Sylvain Richard
Přispěvatelé: Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Universidade Federal de Ouro Preto (UFOP), Université Saint-Joseph de Beyrouth (USJ), EA4278 Laboratoire de Pharm-Ecologie Cardiovasculaire (LaPEC), Avignon Université (AU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des adaptations cardiovasculaires à l'Exercice, Physiopathologie cardiovasculaire, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), MORNET, Dominique
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Heart Ventricles
[SDV]Life Sciences [q-bio]
Diastole
Concentric hypertrophy
030204 cardiovascular system & hematology
Ryanodine receptor 2
Sodium-Calcium Exchanger
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Ventricular Dysfunction
Left
03 medical and health sciences
0302 clinical medicine
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Internal medicine
medicine
Animals
Myocytes
Cardiac
Rats
Wistar
Molecular Biology
Heart Failure
Homeodomain Proteins
Pressure overload
Cardiomyocytes
Ejection fraction
business.industry
Calcium-Binding Proteins
Ryanodine Receptor Calcium Release Channel
Stroke Volume
medicine.disease
Rats
Phospholamban
[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Disease Models
Animal
Sarcoplasmic Reticulum
030104 developmental biology
Heart failure with preserved ejection fraction
Heart failure
Hypertension
Cardiology
cardiovascular system
Molecular Medicine
Calcium
Calcium-Calmodulin-Dependent Protein Kinase Type 2
business
Zdroj: Biochimica et Biophysica Acta-Molecular Basis of Disease
Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2019, 1865 (1), pp.230-242. ⟨10.1016/j.bbadis.2018.08.005⟩
Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2018, 1865 (1), pp.230-242. ⟨10.1016/j.bbadis.2018.08.005⟩
Biochimica et Biophysica Acta-Molecular Basis of Disease, 2019, 1865 (1), pp.230-242. ⟨10.1016/j.bbadis.2018.08.005⟩
ISSN: 0925-4439
DOI: 10.1016/j.bbadis.2018.08.005⟩
Popis: International audience; Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high morbidity and mortality. Therapeutic options are limited due to a lack of knowledge of the pathology and its evolution. 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 Sodium/Calcium exchanger (NCX), which promoted an increase in diastolic Ca2+. The Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2a) and NCX protein levels were unchanged. The phospholamban (PLN) to SERCA2a ratio was augmented in favor of an inhibitory effect on the SERCA2a activity. Conversely, PLN phosphorylation at the calmodulin-dependent kinase II (CaMKII)-specific site (PLN-Thr17), which promotes SERCA2A activity, was increased as well, suggesting an adaptive compensation of Ca2+ cycling. Altogether our findings show that cardiac remodeling in hearts with a HFpEF status differs from that known for heart failure with reduced ejection fraction. These data also underscore the interdependence between systolic and diastolic "adaptations" of Ca2+ cycling with complex compensative interactions between Ca2+ handling partner and regulatory proteins.
Databáze: OpenAIRE
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