A novel mouse model of calcific aortic valve stenosis  

作　　者：Ningjing Qian Yaping Wang Wangxing Hu Naifang Cao Yi Qian Jinyong Chen Juan Fang Dilin Xu Haochang Hu Shuangshuang Yang Dao Zhou Hanyi Dai Dongdong Wei Jian'an Wang Xianbao Liu 

机构地区：[1]Department of Cardiology,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [2]State Key Laboratory of Transvascular Implantation Devices,China [3]Cardiovascular Key Laboratory of Zhejiang Province,Hangzhou,China [4]Department of Cardiovascular Surgery,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [5]Department of Endocrinology,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [6]Binjiang Institute of Zhejiang University,Hangzhou,China

出　　处：《Animal Models and Experimental Medicine》2024年第4期523-532,共10页动物模型与实验医学（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Number:81770252,82030014,82271606 and U22A20267;Binjiang Institute of Zhejiang University,Grant/Award Number:ZY202205SMKY001;Key Program of Major Science and Technology Projects in Zhejiang Province,Grant/Award Number:2021C03097 and 2022C03063。

摘　　要：Background:Calcific aortic valve stenosis(CAVS)is one of the most challenging heart diseases in clinical with rapidly increasing prevalence.However,study of the mecha-nism and treatment of CAVS is hampered by the lack of suitable,robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposi-tion.Here,we aim to establish a mouse model to mimic the development and features of CAVS.Methods: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 gradi-ent.Histopathological specimens were collected and examined in respect of valve thickening,calcium deposition,collagen accumulation,osteogenic differentiation and inflammation.Results:Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time depend-ent manner and tended to be stable at 28 days.Compared with the sham group,sim-ple AVWI or the vitamin D group,the hybrid model group showed typical pathological features of CAVS,including hemodynamic alterations,increased aortic valve thicken-ing,calcium deposition,collagen accumulation at 28 days.In addition,osteogenic dif-ferentiation,fibrosis and inflammation,which play critical roles in the development of CAVS,were observed in the hybrid model.Conclusions: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 effec-tive pharmacological targets.

关 键 词：animal model calcific aortic valve stenosis valve calcification 

分 类 号：R542.52[医药卫生—心血管疾病] R-332[医药卫生—内科学]