Journal article
Discovery of an Experimental Model of Unicuspid Aortic Valve
Journal of the American Heart Association, Vol.7(13), e006908
06/30/2018
DOI: 10.1161/JAHA.117.006908
PMCID: PMC6064885
PMID: 29960994
Abstract
The epithelial growth factor receptor family of tyrosine kinases modulates embryonic formation of semilunar valves. We hypothesized that mice heterozygous for a dominant loss-of-function mutation in epithelial growth factor receptor, which are
mice, would develop anomalous aortic valves, valve dysfunction, and valvular cardiomyopathy.
Aortic valves from
mice and control mice were examined by light microscopy at 2.5 to 4 months of age. Additional
and control mice underwent echocardiography at 2.5, 4.5, 8, and 12 months of age, followed by histologic examination. In young mice, microscopy revealed anatomic anomalies in 79% of
aortic valves, which resembled human unicuspid aortic valves. Anomalies were not observed in control mice. At 12 months of age, histologic architecture was grossly distorted in
aortic valves. Echocardiography detected moderate or severe aortic regurgitation, or aortic stenosis was present in 38% of
mice at 2.5 months of age (N=24) and in 74% by 8 months of age. Left ventricular enlargement, hypertrophy, and reversion to a fetal myocardial gene expression program occurred in
mice with aortic valve dysfunction, but not in
mice with near-normal aortic valve function. Myocardial fibrosis was minimal or absent in all groups.
A new mouse model uniquely recapitulates salient functional, structural, and histologic features of human unicuspid aortic valve disease, which are phenotypically distinct from other forms of congenital aortic valve disease. The new model may be useful for elucidating mechanisms by which congenitally anomalous aortic valves become critically dysfunctional.
Details
- Title: Subtitle
- Discovery of an Experimental Model of Unicuspid Aortic Valve
- Creators
- Robert M Weiss - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IA robert-weiss@uiowa.eduYi Chu - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IARobert M Brooks - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IADonald D Lund - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IAJustine Cheng - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IAKathy A Zimmerman - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IAMelissa K Kafa - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IAPhanicharan Sistla - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IAHardik Doshi - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IAJian Q Shao - The Central Microscopy Core, Carver College of Medicine University of Iowa, Iowa City, IARamzi N El Accaoui - Division of Cardiovascular Medicine, Carver College of Medicine University of Iowa, Iowa City, IACatherine M Otto - Division of Cardiology, University of Washington School of Medicine, Seattle, WADonald D Heistad - Department of Pharmacology, Carver College of Medicine University of Iowa, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Journal of the American Heart Association, Vol.7(13), e006908
- DOI
- 10.1161/JAHA.117.006908
- PMID
- 29960994
- PMCID
- PMC6064885
- ISSN
- 2047-9980
- eISSN
- 2047-9980
- Grant note
- S10 OD019941 / NIH HHS
- Language
- English
- Date published
- 06/30/2018
- Academic Unit
- Radiology; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984094217502771
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