ArticleAmerican journal of physiology. Heart and circulatory physiology2009
Reduced EGFR causes abnormal valvular differentiation leading to calcific aortic stenosis and left ventricular hypertrophy in C57BL/6J but not 129S1/SvImJ mice.
Article in American journal of physiology. Heart and circulatory physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Aortic valve disease: Novel animal models for advancing our understanding of the underlying mechanisms.Animal models and experimental medicine · 2026Review
- Serum proteomics mirrors the histopathological changes underlying different etiologies of primary mitral valve disease.Bioscience reports · 2026Article
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025Review
- Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages.Annals of biomedical engineering · 2024Article
- Cytoplasmic retention of the DNA/RNA-binding protein FUS ameliorates organ fibrosis in mice.The Journal of clinical investigation · 2024Article
- Myeloid cell-specific deletion of epidermal growth factor receptor aggravates acute cardiac injury.Clinical science (London, England : 1979) · 2023Article
- Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve Stenosis.Circulation · 2023Article
- Cardiac Remodelling Following Cancer Therapy: A Review.Cardiovascular toxicology · 2022Review
- Epidermal growth factor receptor-dependent maintenance of cardiac contractility.Cardiovascular research · 2022Article
- The two facets of receptor tyrosine kinase in cardiovascular calcification-can tyrosine kinase inhibitors benefit cardiovascular system?Frontiers in cardiovascular medicine · 2022Review
- Models and Techniques to Study Aortic Valve CalcificationFrontiers in pharmacology · 2022Review
- Epithelial-specific ERBB3 deletion results in a genetic background-dependent increase in intestinal and colon polyps that is mediated by EGFR.PLoS genetics · 2021Article
- The mineralocorticoid receptor leads to increased expression of EGFR and T-type calcium channels that support HL-1 cell hypertrophy.Scientific reports · 2021Article
- Multi-Omics Approaches to Define Calcific Aortic Valve Disease Pathogenesis.Circulation research · 2021Review
- A Genomic Study of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels.Animals : an open access journal from MDPI · 2020Article
- Harnessing Mechanosensation in Next Generation Cardiovascular Tissue Engineering.Biomolecules · 2020Review
- Calcific Aortic Valve Disease: a Developmental Biology Perspective.Current cardiology reports · 2018Review
- Essential role for EGFR tyrosine kinase and ER stress in myocardial infarction in type 2 diabetes.Pflugers Archiv : European journal of physiology · 2018Article
- Proteomic Alterations Associated with Biomechanical Dysfunction are Early Processes in the Emilin1 Deficient Mouse Model of Aortic Valve Disease.Annals of biomedical engineering · 2017Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) signaling contributes to aortic valve development in mice. Because developmental phenotypes in Egfr-null mice are dependent on genetic background, the hypomorphic Egfr(wa2) allele was made congenic on C57BL/6J (B6) and 129S1/SvImJ (129) backgrounds and used to identify the underlying cellular cause of EGFR-related aortic valve abnormalities. Egfr(wa2/wa2) mice on both genetic backgrounds develop aortic valve hyperplasia. Many B6-Egfr(wa2/wa2) mice die before weaning, and those surviving to 3 mo of age or older develop severe left ventricular hypertrophy and heart failure. The cardiac phenotype was accompanied by significantly thicker aortic cusps and larger transvalvular gradients in B6-Egfr(wa2/wa2) mice compared with heterozygous controls and age-matched Egfr(wa2) homozygous mice on either 129 or B6129F1 backgrounds. Histological analysis revealed cellular changes in B6-Egfr(wa2/wa2) aortic valves underlying elevated pressure gradients and progression to heart failure, including increased cellular proliferation, ectopic cartilage formation, extensive calcification, and inflammatory infiltrate, mimicking changes seen in human calcific aortic stenosis. Despite having congenitally enlarged valves, 129 and B6129F1-Egfr(wa2/wa2) mice have normal lifespans, absence of left ventricular hypertrophy, and normal systolic function. These results show the requirement of EGFR activity for normal valvulogenesis and demonstrate that dominantly acting genetic modifiers curtail pathological changes in congenitally deformed valves. These studies provide a novel model of aortic sclerosis and stenosis and suggest that long-term inhibition of EGFR signaling for cancer therapy may have unexpected consequences on aortic valves in susceptible individuals.
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