Echocardiographic characterization of a murine model of hypertrophic obstructive cardiomyopathy induced by cardiac-specific overexpression of epidermal growth factor receptor 2

Lars L. Sørensen, Djahida Bedja, Polina Sysa-Shah, Hongyun Liu, Amanda Maxwell, Xu Yi, Iraklis Pozios, Niels T. Olsen, Theodore P. Abraham, Roselle Abraham, Kathleen Gabrielson*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 (ErbB2tg) 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 ErbB2tg mouse line as a model of HCM. Compared with their wild-type littermates, ErbB2tg 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, ErbB2tg 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 ErbB2tg 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 ErbB2tg compared with wild-type mice. In conclusion, the phenotype of the ErbB2tg 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 ErbB2tg mice may be well suited for research into the hemodynamics and treatment of this rare form of HCM.

Original languageEnglish
Pages (from-to)268-277
Number of pages10
JournalComparative Medicine
Volume66
Issue number4
Publication statusPublished - 1 Aug 2016
Externally publishedYes

Fingerprint Dive into the research topics of 'Echocardiographic characterization of a murine model of hypertrophic obstructive cardiomyopathy induced by cardiac-specific overexpression of epidermal growth factor receptor 2'. Together they form a unique fingerprint.

  • Cite this