title: Echocardiographic Characterization of a Murine Model of Hypertrophic Obstructive Cardiomyopathy Induced by Cardiac-specific Overexpression of Epidermal Growth Factor Receptor 2.
abstract: Although rare, hypertrophic cardiomyopathy (HCM) with midventricular obstruction is often associated with severe symptoms and complications. None of the existing HCM animal models display this particular phenotype. Our group developed a mouse line that overexpresses the ErbB2 receptor (ErbB2(tg)) in cardiomyocytes; we previously showed that the ErbB2 receptor induces cardiomyocyte hypertrophy, myocyte disarray, and fibrosis compatible with HCM. In the current study, we sought to further echocardiographically characterize the ErbB2(tg) mouse line as a model of HCM. Compared with their wild-type littermates, ErbB2(tg) mice show increased left ventricular (LV) mass, concentric LV hypertrophy, and papillary muscle hypertrophy. This hypertrophy was accompanied by diastolic dysfunction, expressed as reduced E:A ratio, prolonged deceleration time, and elevated E:e' ratio. In addition, ErbB2(tg) mice consistently showed midcavity obstruction with elevated LV gradients, and the flow profile revealed a prolonged pressure increase and a delayed peak, indicating dynamic obstruction. The ejection fraction was increased in ErbB2(tg) mice, due to reduced end-diastolic and end-systolic LV volumes. Furthermore, systolic radial strain and systolic radial strain rate but not systolic circumferential strain and longitudinal strain were decreased in ErbB2(tg) compared with wild-type mice. In conclusion, the phenotype of the ErbB2(tg) mouse model is consistent with midventricular HCM in many important aspects, including massive LV hypertrophy, diastolic dysfunction, and midcavity obstruction. This pattern is unique for a small animal model, suggesting that ErbB2(tg) mice may be well suited for research into the hemodynamics and treatment of this rare form of HCM.
authors.affiliation: Department of Cardiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA; Department of Cardiology, Gentofte Hospital, Copenhagen, Denmark.
authors.forename: Lars L
authors.initials: LL
authors.lastname: Sørensen
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Djahida
authors.initials: D
authors.lastname: Bedja
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Polina
authors.initials: P
authors.lastname: Sysa-Shah
authors.affiliation: Department of Cardiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Maxwell
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Cardiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Iraklis
authors.initials: I
authors.lastname: Pozios
authors.affiliation: Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Niels T
authors.initials: NT
authors.lastname: Olsen
authors.affiliation: Department of Cardiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Abraham
authors.affiliation: Department of Cardiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Roselle
authors.initials: R
authors.lastname: Abraham
authors.affiliation: Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. kgabriel@jhmi.edu.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gabrielson
mesh_terms: D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging* / Q000209:etiology* / Q000503:physiopathology; D003971:Diastole; D004195:Disease Models, Animal; D018618:Echocardiography, Doppler, Color; D018619:Echocardiography, Doppler, Pulsed; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism; D010210:Papillary Muscles / Q000000981:diagnostic imaging / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013599:Systole
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; C524056:Erbb2 protein, mouse