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However, no effective medications have been approved to slow or prevent the progression of CAVD. Here, we examined the effect of liraglutide on aortic valve stenosis. Methods: Male Apoe\u2212\/\u2212 mice were fed with a high-cholesterol diet for 24 weeks to generate an experimental CAVD model and randomly assigned to a liraglutide treatment group or control group. Echocardiography and immunohistological analyses were performed to examine the aortic valve function and morphology, fibrosis, and calcium deposition. Plasma Glucagon-like peptide-1 (GLP-1) levels and inflammatory contents were measured via ELISA, FACS, and immunofluorescence. RNA sequencing (RNA-seq) was used to identify liraglutide-affected pathways and processes. Results: Plasma GLP-1 levels were reduced in the CAVD model, and liraglutide treatment significantly improved aortic valve calcification and functions and attenuated inflammation. RNA-seq showed that liraglutide affects multiple myofibroblastic and osteogenic differentiations or inflammation-associated biological states or processes in the aortic valve. Those liraglutide-mediated beneficial effects were associated with increased GLP-1 receptor (GLP-1R) expression. Conclusions: Liraglutide blocks aortic valve calcification and may serve as a potential therapeutic drug for CAVD treatment.<\/jats:p>","DOI":"10.3390\/jcdd10090386","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T10:14:14Z","timestamp":1693995254000},"page":"386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Liraglutide Attenuates Aortic Valve Calcification in a High-Cholesterol-Diet-Induced Experimental Calcific Aortic Valve Disease Model in Apolipoprotein E-Deficient Mice"],"prefix":"10.3390","volume":"10","author":[{"given":"Yangzhao","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoshun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changming","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaolian","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Sayed","family":"Ali Sheikh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-8215","authenticated-orcid":false,"given":"Dafeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"ref_1","first-page":"e28","article-title":"Heart disease and stroke statistics\u20142014 update: A report from the American Heart Association","volume":"129","author":"Go","year":"2014","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1056\/NEJMra1313875","article-title":"Aortic-valve stenosis from patients at risk to severe valve obstruction","volume":"371","author":"Otto","year":"2014","journal-title":"N. 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