{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:01:51Z","timestamp":1777633311602,"version":"3.51.4"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Calcific aortic valve disease (CAVD) is a common valvular heart disorder for which effective pharmacological treatments remain lacking. This study aimed to compare the expression and potential pathophysiological relevance of glucagon-like peptide-1 receptor (GLP1R), proprotein convertase subtilisin\/kexin type 9 (PCSK9), and sodium-glucose cotransporter 2 (SGLT2) in human aortic valve (AV) and mitral valve (MV) tissues from patients undergoing valve replacement surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Surgically resected AV (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) and MV (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913) tissue specimens were collected between March 2020 and December 2022. Target protein expression was assessed via immunohistochemistry (IHC), and valvular calcification was confirmed by Von Kossa staining. Subgroup analyses were performed within calcified vs. non-calcified AV tissues and within a bicuspid aortic valve (BAV) subset (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093 per group).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GLP1R, PCSK9, and SGLT2 expression levels were significantly elevated in AV tissues compared to MV tissues (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001). Within calcified AV specimens, expression trends were higher than in non-calcified AV tissues, though these differences did not reach statistical difference (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;gt;\u20090.05). In the exploratory BAV subgroup (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093 per group), expression of all three targets was higher in calcified vs. non-calcified tissues (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings reflect differential expression between anatomically distinct valve types and do not establish CAVD-specific upregulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1813717","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:33:30Z","timestamp":1777437210000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential expression of GLP1R, PCSK9, and SGLT2 in human aortic versus mitral valve tissues: exploratory findings in calcific aortic valve disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Shou-Quan","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Cardiology, Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]},{"name":"Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nai-Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"C29","DOI":"10.1152\/ajpcell.00384.2007","article-title":"Expression of functional toll-like receptors 2 and 4 in human aortic valve interstitial cells: potential roles in aortic valve inflammation and stenosis","volume":"294","author":"Meng","year":"2008","journal-title":"Am J Physiol Cell Physiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.ijcard.2015.04.086","article-title":"The protective effect of GLP-1 analogue in arterial calcification through attenuating osteoblastic differentiation of human VSMCs","volume":"189","author":"Zhan","year":"2015","journal-title":"Int J Cardiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41514-018-0026-2","article-title":"The annual rate of coronary artery calcification with combination 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Adv"},{"key":"B10","doi-asserted-by":"publisher","first-page":"6411","DOI":"10.3390\/jcm13216411","article-title":"Effect of glucagon-like peptide-1 receptor agonism on aortic valve stenosis risk: a Mendelian randomization analysis","volume":"13","author":"Karakasis","year":"2024","journal-title":"J Clin Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1016\/j.jacc.2018.09.063","article-title":"PCSK9 Involvement in aortic valve calcification","volume":"72","author":"Poggio","year":"2018","journal-title":"J Am Coll Cardiol"}],"container-title":["Frontiers in Cardiovascular 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