{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:20:34Z","timestamp":1776856834437,"version":"3.51.2"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              A series of incurable cardiovascular disorders arise due to improper formation of elastin during development. Supravalvular aortic stenosis (SVAS), resulting from a haploinsufficiency of\n              <jats:italic toggle=\"yes\">ELN<\/jats:italic>\n              , 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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We use SVAS here as a model of vascular proliferative disease using both human induced pluripotent stem cell\u2013derived vascular smooth muscle cells and developmental\n              <jats:italic toggle=\"yes\">Eln<\/jats:italic>\n              <jats:sup>+\/\u2013<\/jats:sup>\n              mouse models to establish de novo elastin assembly as a new therapeutic intervention.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              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\u2013derived vascular smooth muscle cells and in utero to\n              <jats:italic toggle=\"yes\">Eln<\/jats:italic>\n              <jats:sup>+\/\u2013<\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              We demonstrate de novo elastin deposition normalizes SVAS human induced pluripotent stem cell\u2013derived vascular smooth muscle cell hyperproliferation and rescues hypertension and aortic mechanics in\n              <jats:italic toggle=\"yes\">Eln<\/jats:italic>\n              <jats:sup>+\/\u2013<\/jats:sup>\n              mice, providing critical preclinical findings for the future application of epigallocatechin gallate treatment in humans.\n            <\/jats:p>\n          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Cellular and Molecular Physiology (M.W.E.), Yale University, New Haven, CT."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0311-8392","authenticated-orcid":true,"given":"Muhammad","family":"Riaz","sequence":"additional","affiliation":[{"name":"Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine (M.W.E., M.R., Y.H., C.W.A., M.H., X.L., H.L., J.P., J.L., L.D.B., C.A.L., Y.Q.), Yale School of Medicine, New Haven, CT."},{"name":"Yale Stem Cell Center, New Haven, CT (M.W.E., M.R., Y.H., C.W.A., M.H., X.L., H.L., J.P., J.L., L.D.B., C.A.L., Y.Q.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine (M.W.E., M.R., Y.H., C.W.A., M.H., X.L., H.L., J.P., J.L., L.D.B., C.A.L., Y.Q.), Yale School of Medicine, New Haven, CT."},{"name":"Yale Stem Cell Center, New Haven, CT (M.W.E., M.R., Y.H., C.W.A., M.H., X.L., H.L., J.P., J.L., L.D.B., C.A.L., Y.Q.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0801-5341","authenticated-orcid":true,"given":"Christopher W.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine (M.W.E., M.R., Y.H., C.W.A., M.H., X.L., H.L., J.P., J.L., L.D.B., C.A.L., Y.Q.), Yale School of Medicine, New Haven, CT."},{"name":"Yale Stem Cell Center, New Haven, CT (M.W.E., M.R., Y.H., C.W.A., M.H., X.L., H.L., J.P., J.L., L.D.B., C.A.L., Y.Q.)."},{"name":"Department of Pathology (C.W.A., L.D.B., Y.Q.), Yale University, New Haven, 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