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However, study of the mechanism and treatment of CAVS is hampered by the lack of suitable, robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposition. Here, we aim to establish a mouse model to mimic the development and features of CAVS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The model was established via aortic valve wire injury (AVWI) combined with vitamin D subcutaneous injected in wild type C57\/BL6 mice. Serial transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean gradient. Histopathological specimens were collected and examined in respect of valve thickening, calcium deposition, collagen accumulation, osteogenic differentiation and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7\u2009days post model establishment in a time dependent manner and tended to be stable at 28\u2009days. Compared with the sham group, simple AVWI or the vitamin D group, the hybrid model group showed typical pathological features of CAVS, including hemodynamic alterations, increased aortic valve thickening, calcium deposition, collagen accumulation at 28\u2009days. In addition, osteogenic differentiation, fibrosis and inflammation, which play critical roles in the development of CAVS, were observed in the hybrid model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We established a novel mouse model of CAVS that could be induced efficiently, robustly and economically, and without genetic intervention. It provides a fast track to explore the underlying mechanisms of CAVS and to identify more effective pharmacological targets.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12393","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T11:41:15Z","timestamp":1708342875000},"page":"523-532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel mouse model of calcific aortic valve stenosis"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8707-2757","authenticated-orcid":false,"given":"Ningjing","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Cardiology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"},{"name":"State Key Laboratory of Transvascular Implantation Devices  China"},{"name":"Cardiovascular Key Laboratory of Zhejiang Province  Hangzhou 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