{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:19:41Z","timestamp":1790752781285,"version":"4.1.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["ZIA HL006210"],"award-info":[{"award-number":["ZIA HL006210"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["ZIA HL-006247"],"award-info":[{"award-number":["ZIA HL-006247"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Williams Beuren syndrome (WBS) is a recurrent microdeletion disorder that removes one copy of elastin (<jats:italic>ELN<\/jats:italic>), resulting in large artery vasculopathy. Early stenosis of the pulmonary vascular tree is common, but few data are available on longer-term implications of the condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Computed tomography (CT) angiogram (<jats:italic>n<\/jats:italic> = 11) and echocardiogram (<jats:italic>n<\/jats:italic> = 20) were performed in children with WBS aged 3.4\u201317.8 years. Controls (<jats:italic>n<\/jats:italic> = 11, aged 4.4\u201316.8 years) also underwent echocardiogram. <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice were analyzed by invasive catheter, echocardiogram, micro-CT (\u03bcCT), histology, and pressure myography. We subsequently tested whether minoxidil resulted in improved pulmonary vascular endpoints.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WBS participants with a history of main or branch pulmonary artery (PA) stenosis requiring intervention continued to exhibit increased right ventricular systolic pressure (RVSP, echocardiogram) relative to their peers without intervention (<jats:italic>p<\/jats:italic> &amp;lt; 0.01), with no clear difference in PA size. Untreated <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice also show elevated RVSP by invasive catheterization (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001), increased normalized right heart mass (<jats:italic>p<\/jats:italic> &amp;lt; 0.01) and reduced caliber branch PAs by pressure myography (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001). <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> main PA medias are thickened histologically relative to <jats:italic>Eln<\/jats:italic><jats:sup>+\/+<\/jats:sup> (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001). Most <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> phenotypes are shared by both sexes, but PA medial thickness is substantially greater in <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> males (<jats:italic>p<\/jats:italic> &amp;lt; 0.001). <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice showed more acute proximal branching angles (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001) and longer vascular segment lengths (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001) (\u03bcCT), with genotype differences emerging by P7. Diminished PA acceleration time (<jats:italic>p<\/jats:italic> &amp;lt; 0.001) and systolic notching (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001) were also observed in <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> echocardiography. Vascular casting plus \u03bcCT revealed longer generation-specific PA arcade length (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001), with increased PA branching detectable by P90 (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001). Post-weaning minoxidil decreased RVSP (<jats:italic>p<\/jats:italic> &amp;lt; 0.01) and normalized PA caliber (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001) but not early-onset proximal branching angle or segment length, nor later-developing peripheral branch number.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Vascular deficiencies beyond arterial caliber persist in individuals with WBS who have undergone PA stenosis intervention. Evaluation of <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice reveals complex vascular changes that affect the proximal and distal vasculatures. Minoxidil, given post-weaning, decreases RVSP and improves lumen diameter, but does not alter other earlier-onset vascular patterns. Our data suggest additional therapies including minoxidil could be a useful adjunct to surgical therapy, and future trials should be considered.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.886813","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T05:34:23Z","timestamp":1652938463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Elastin Insufficiency Confers Proximal and Distal Pulmonary Vasculopathy in Mice, Partially Remedied by the KATP Channel Opener Minoxidil: Considerations and Cautions for the Treatment of People With Williams-Beuren Syndrome"],"prefix":"10.3389","volume":"9","author":[{"given":"Russell H.","family":"Knutsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah M.","family":"Gober","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise 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