ArticleThe Journal of experimental medicine2016
Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Sphingosine kinase 1 is integral for elastin deficiency-induced arterial hypermuscularization.Nature cardiovascular research · 2026Article
- Elastin Regulation of Vasoreactivity in Resistance Arteries.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Switching Roles─Exploring Concentration-Dependent Agonistic versus Antagonistic Behavior of Integrin Ligands.Journal of medicinal chemistry · 2025Article
- De Novo Elastin Assembly Alleviates Development of Supravalvular Aortic Stenosis-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Matrisome and Immune Pathways Contribute to Extreme Vascular Outcomes in Williams-Beuren Syndrome.Journal of the American Heart Association · 2024Article
- Presenilin-1 in smooth muscle cells facilitates hypermuscularization in elastin aortopathy.iScience · 2024Article
- Cystathionine Gamma Lyase Is Regulated by Flow and Controls Smooth Muscle Migration in Human Saphenous Vein.Antioxidants (Basel, Switzerland) · 2023Article
- Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Structure-Based Discovery of a Novel Class of Small-Molecule Pure Antagonists of Integrin αVβ3.Journal of chemical information and modeling · 2022Article
- Elastin, arterial mechanics, and stenosis.American journal of physiology. Cell physiology · 2022Review
- JAGGED1/NOTCH3 activation promotes aortic hypermuscularization and stenosis in elastin deficiency.The Journal of clinical investigation · 2022Article
- Vascular Smooth Muscle Cell Subpopulations and Neointimal Formation in Mouse Models of Elastin Insufficiency.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Williams syndrome.Nature reviews. Disease primers · 2021Review
- Human iPS Cell-derived Tissue Engineered Vascular Graft: Recent Advances and Future Directions.Stem cell reviews and reports · 2021Review
- Review
- Targeting smooth muscle cell phenotypic switching in vascular disease.JVS-vascular science · 2021Review
- Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxia-induced apoptosis via regulating the PTEN/Akt/mTOR and ERK1/2 pathways.International journal of biological sciences · 2020Article
- Novel Pure αVβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations.ACS pharmacology & translational science · 2019Article
- Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis.Molecular genetics & genomic medicine · 2019Article
- Modeling elastin-associated vasculopathy with patient induced pluripotent stem cells and tissue engineering.Cellular and molecular life sciences : CMLS · 2019Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
The aorta is the largest artery in the body, yet processes underlying aortic pathology are poorly understood. The arterial media consists of circumferential layers of elastic lamellae and smooth muscle cells (SMCs), and many arterial diseases are characterized by defective lamellae and excess SMCs; however, a mechanism linking these pathological features is lacking. In this study, we use lineage and genetic analysis, pharmacological inhibition, explant cultures, and induced pluripotent stem cells (iPSCs) to investigate supravalvular aortic stenosis (SVAS) patients and/or elastin mutant mice that model SVAS. These experiments demonstrate that multiple preexisting SMCs give rise to excess aortic SMCs in elastin mutants, and these SMCs are hyperproliferative and dedifferentiated. In addition, SVAS iPSC-derived SMCs and the aortic media of elastin mutant mice and SVAS patients have enhanced integrin β3 levels, activation, and downstream signaling, resulting in SMC misalignment and hyperproliferation. Reduced β3 gene dosage in elastin-null mice mitigates pathological aortic muscularization, SMC misorientation, and lumen loss and extends survival, which is unprecedented. Finally, pharmacological β3 inhibition in elastin mutant mice and explants attenuates aortic hypermuscularization and stenosis. Thus, integrin β3-mediated signaling in SMCs links elastin deficiency and pathological stenosis, and inhibiting this pathway is an attractive therapeutic strategy for SVAS.
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