{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:49:40Z","timestamp":1790779780722,"version":"4.1.0"},"reference-count":71,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["R01HL151190,R01HL146149"],"award-info":[{"award-number":["R01HL151190,R01HL146149"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NICHD","award":["R01HD090132"],"award-info":[{"award-number":["R01HD090132"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["7POST33670699"],"award-info":[{"award-number":["7POST33670699"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,8]]},"abstract":"<jats:p>\n                    Calcific aortic valve disease (CAVD) is heritable, as revealed by recent GWAS. While polymorphisms linked to increased expression of\n                    <jats:italic>CACNA1C<\/jats:italic>\n                    \u2014 encoding the Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 L-type voltage-gated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel \u2014 and increased Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling are associated with CAVD, whether increased Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through the druggable Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 causes CAVD is unknown. We confirmed the association between increased Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 expression and CAVD in surgically removed aortic valves from patients. We extended our studies with a transgenic mouse model that mimics increased Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 expression within aortic valve interstitial cells (VICs). In young mice maintained on normal chow, we observed dystrophic valve lesions that mimic changes found in presymptomatic CAVD and showed activation of chondrogenic and osteogenic transcriptional regulators within these valve lesions. Chronic administration of verapamil, a Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 antagonist used clinically, slowed the progression of lesion development in vivo. Exploiting VIC cultures, we demonstrated that increased Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 drives signaling programs that lead to myofibroblast activation of VICs and upregulation of genes associated with aortic valve calcification. Our data support a causal role for Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 in CAVD and suggest that early treatment with Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel blockers is an effective therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.155569","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T12:06:05Z","timestamp":1643717165000},"source":"Crossref","is-referenced-by-count":19,"title":["Increased Ca2+ influx through CaV1.2 drives aortic valve calcification"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9706-8244","authenticated-orcid":true,"given":"Maiko","family":"Matsui","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, Weill Cornell Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rihab","family":"Bouchareb","sequence":"additional","affiliation":[{"name":"Zena and Michael A. 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