Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul;44(7):1674-1682.
doi: 10.1161/ATVBAHA.124.320790. Epub 2024 May 16.

De Novo Elastin Assembly Alleviates Development of Supravalvular Aortic Stenosis-Brief Report

Matthew W Ellis #  1   2   3 , Muhammad Riaz #  1   2 , Yan Huang  1   2 , Christopher W Anderson  1   2   4 , Marie Hoareau  1   2 , Xin Li  1   2 , Hangqi Luo  1   2 , Seoyeon Lee  5 , Jinkyu Park  1   2 , Jiesi Luo  1   2 , Luke D Batty  1   2   4 , Qunhua Huang  6 , Colleen A Lopez  1   2 , Dieter P Reinhardt  7 , George Tellides  6   8 , Yibing Qyang  1   6   2   4
Affiliations

De Novo Elastin Assembly Alleviates Development of Supravalvular Aortic Stenosis-Brief Report

Matthew W Ellis et al. Arterioscler Thromb Vasc Biol. 2024 Jul.

Abstract

Background: A series of incurable cardiovascular disorders arise due to improper formation of elastin during development. Supravalvular aortic stenosis (SVAS), resulting from a haploinsufficiency of ELN, is caused by improper stress sensing by medial vascular smooth muscle cells, leading to progressive luminal occlusion and heart failure. SVAS remains incurable, as current therapies do not address the root issue of defective elastin.

Methods: We use SVAS here as a model of vascular proliferative disease using both human induced pluripotent stem cell-derived vascular smooth muscle cells and developmental Eln+/- mouse models to establish de novo elastin assembly as a new therapeutic intervention.

Results: We demonstrate mitigation of vascular proliferative abnormalities following de novo extracellular elastin assembly through the addition of the polyphenol epigallocatechin gallate to SVAS human induced pluripotent stem cell-derived vascular smooth muscle cells and in utero to Eln+/- mice.

Conclusions: We demonstrate de novo elastin deposition normalizes SVAS human induced pluripotent stem cell-derived vascular smooth muscle cell hyperproliferation and rescues hypertension and aortic mechanics in Eln+/- mice, providing critical preclinical findings for the future application of epigallocatechin gallate treatment in humans.

Keywords: aortic stenosis, supravalvular; elastin; epigallocatechin gallate; induced pluripotent stem cells; polyphenols.

PubMed Disclaimer

Conflict of interest statement

Disclosures M.W. Ellis, J. Luo, and Y. Qyang have filed a patent related to the usage of the polyphenol compound epigallocatechin gallate in the formation of extracellular elastic fibers for the purposes of tissue engineering. The other authors report no conflicts.

Similar articles

See all similar articles

References

    1. Lusis AJ. Atherosclerosis. Nature. 2000;407:233–241. doi:10.1038/35025203 - DOI - PMC - PubMed
    1. Marx SO, Totary-Jain H, Marks AR. Vascular Smooth Muscle Cell Proliferation in Restenosis. Circ Cardiovasc Interv. 2011;4:104–111. doi:10.1161/CIRCINTERVENTIONS.110.957332 - DOI - PMC - PubMed
    1. Pober BR, Johnson M, Urban Z. Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome. Journal of Clinical Investigation. 2008;118:1606–1615. doi:10.1172/JCI35309 - DOI - PMC - PubMed
    1. Wagenseil JE, Mecham RP. Vascular Extracellular Matrix and Arterial Mechanics. Physiol Rev. 2009;89:957–989. doi:10.1152/physrev.00041.2008 - DOI - PMC - PubMed
    1. Jiao Y, Li G, Li Q, et al. mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice. Arterioscler Thromb Vasc Biol. 2017;37:1657–1666. doi:10.1161/ATVBAHA.117.309653 - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources