title: MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression.
abstract: The cardiopathogenic role of autoantibodies (aabs) directed against β1-adrenoreceptors (β1-AR) is well established. In mouse models, they cause progressive dilated cardiomyopathy (DCM) whose characterization with echocardiography requires prolonged protocols with numerous animals, complicating the evaluation of new treatments. Here, we report on the characterization of β1-aabs-induced DCM in mice using 11.7T MRI. C57BL/6J mice (n = 10 per group) were immunized against the β1-AR and left ventricular (LV) systolic function was assessed at 10, 18 and 27 weeks. Increase in LV mass/tibial length ratio was detected as the first modification at 10 weeks together with dilation of cavities, thereby outperforming echocardiography. Significant impairment in diastolic index was also observed in immunized animals before the onset of systolic dysfunction. Morphometric and histological measurements confirmed these observations. The same protocol performed on β3-AR-overexpressing mice and wild-type littermates (n = 8-12 per group) showed that transgenic animals were protected with reduced LV/TL ratio compared to wild-type animals and maintenance of the diastolic index. This study demonstrates that MRI allows a precocious detection of the subtle myocardial dysfunction induced by β1-aabs and that β3-AR stimulation blunts the development of β1-aabs-induced DCM, thereby paving the way for the use of β3AR-stimulating drugs to treat this autoimmune cardiomyopathy.
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.|Department of Paediatric Cardiology, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Vanhoutte
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Guilbaud
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Ruben
authors.initials: R
authors.lastname: Martherus
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.affiliation: Biomedical Magnetic Resonance Unit (REMA), Louvain Drug Research Institute (LDRI), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Dessy
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Balligand
authors.affiliation: Department of Paediatric Cardiology, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Moniotte
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000008:administration & dosage*; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging* / Q000209:etiology / Q000276:immunology*; D004195:Disease Models, Animal; D006321:Heart / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology* / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3