ArticleMechanisms of development
Endothelial deletion of ADAM17 in mice results in defective remodeling of the semilunar valves and cardiac dysfunction in adults.
Article in Mechanisms of development. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Global Adam17 Deficiency Preserves Renal Function and Modulates Integrated Pathogenic Responses in Experimental Diabetic Kidney Disease.International journal of molecular sciences · 2026Article
- Temporal inhibition of ADAM17 in fibroblasts reduces stiffness and promotes vascularization following myocardial infarction.Cardiovascular research · 2026Article
- Ion channels and cardiac disease: mechanisms and functions of a disintegrin and metalloproteases and their substrates.Frontiers in cell and developmental biology · 2026Review
- Article
- Endothelial ADAM17 Expression in the Progression of Kidney Injury in an Obese Mouse Model of Pre-Diabetes.International journal of molecular sciences · 2021Article
- Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes.International journal of molecular sciences · 2021Article
- Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy.International journal of molecular sciences · 2021Article
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- The Endocardium and Heart Valves.Cold Spring Harbor perspectives in biology · 2020Review
- Development and evolution of the metazoan heart.Developmental dynamics : an official publication of the American Association of Anatomists · 2019Review
- Neutrophil and Macrophage Cell Surface Colony-Stimulating Factor 1 Shed by ADAM17 Drives Mouse Macrophage Proliferation in Acute and Chronic Inflammation.Molecular and cellular biology · 2018Article
- Calcific Aortic Valve Disease: a Developmental Biology Perspective.Current cardiology reports · 2018Review
- Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines.The Journal of clinical investigation · 2016Article
- De Novo and Rare Variants at Multiple Loci Support the Oligogenic Origins of Atrioventricular Septal Heart Defects.PLoS genetics · 2016Article
- A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems.Frontiers in physiology · 2016Review
- Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System.Annual review of pharmacology and toxicology · 2016Article
- Loss of ADAM17-Mediated Tumor Necrosis Factor Alpha Signaling in Intestinal Cells Attenuates Mucosal Atrophy in a Mouse Model of Parenteral Nutrition.Molecular and cellular biology · 2015Article
- Spontaneous Aortic Regurgitation and Valvular Cardiomyopathy in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2015Article
- A Lactobacillus rhamnosus GG-derived soluble protein, p40, stimulates ligand release from intestinal epithelial cells to transactivate epidermal growth factor receptor.The Journal of biological chemistry · 2013Article
- A disintegrin and metalloproteinase 17 regulates TNF and TNFR1 levels in inflammation and liver regeneration in mice.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Global inactivation of the metalloproteinase ADAM17 during mouse development results in perinatal lethality and abnormalities of the heart, including late embryonic cardiomegaly and thickened semilunar and atrioventricular valves. These defects have been attributed in part to a lack of ADAM17-mediated processing of HB-EGF, as absence of soluble HB-EGF results in similar phenotypes. Because valvular mesenchymal cells are largely derived from cardiac endothelial cells, we generated mice with a floxed Adam17 allele and crossed these animals with Tie2-Cre transgenics to focus on the role of endothelial ADAM17 in valvulogenesis. We find that although hearts from late-stage embryos with ablation of endothelial ADAM17 appear normal, an increase in valve size and cell number is evident, but only in the semilunar cusps. Unlike Hbegf(-/-) valves, ADAM17-null semilunar valves do not differ from controls in acute cell proliferation at embryonic day 14.5 (E14.5), suggesting compensatory processing of HB-EGF. However, levels of the proteoglycan versican are significantly reduced in mutant hearts early in valve remodeling (E12.5). After birth, aortic valve cusps from mutants are not only hyperplastic but also show expansion of the glycosaminoglycan-rich component, with the majority of adults exhibiting aberrant compartmentalization of versican and increased deposition of collagen. The inability of mutant outflow valve precursors to transition into fully mature cusps is associated with decreased postnatal viability, progressive cardiomegaly, and systolic dysfunction. Together, our data indicate that ADAM17 is required in valvular endothelial cells for regulating cell content as well as extracellular matrix composition and organization in semilunar valve remodeling and homeostasis.
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