A novel mouse model of calcific aortic valve stenosis

Ningjing Qian ¹Yaping Wang ¹Wangxing Hu ¹Naifang Cao ¹Yi Qian ²Jinyong Chen ¹Juan Fang ³Dilin Xu ¹Haochang Hu ¹Shuangshuang Yang ¹Dao Zhou ¹Hanyi Dai ¹Dongdong Wei ⁴Jian'an Wang ⁵Xianbao Liu¹

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作者信息

1. Department of Cardiology,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China;State Key Laboratory of Transvascular Implantation Devices,China;Cardiovascular Key Laboratory of Zhejiang Province,Hangzhou,China
2. State Key Laboratory of Transvascular Implantation Devices,China;Cardiovascular Key Laboratory of Zhejiang Province,Hangzhou,China;Department of Cardiovascular Surgery,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China
3. Department of Endocrinology,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China
4. Department of Cardiovascular Surgery,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China
5. Department of Cardiology,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China;State Key Laboratory of Transvascular Implantation Devices,China;Cardiovascular Key Laboratory of Zhejiang Province,Hangzhou,China;Binjiang Institute of Zhejiang University,Hangzhou,China
折叠

Abstract

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.

Key words

animal model/calcific aortic valve stenosis/valve calcification

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基金项目

National Natural Science Foundation of China(81770252)

National Natural Science Foundation of China(82030014)

National Natural Science Foundation of China(82271606)

National Natural Science Foundation of China(U22A20267)

Binjiang Institute of Zhejiang University(ZY202205SMKY001)

Key Program of Major Science and Technology Projects in Zhejiang Province(2021C03097)

Key Program of Major Science and Technology Projects in Zhejiang Province(2022C03063)

出版年

2024

动物模型与实验医学(英文)

中国实验动物学会,中国医学科学院医学实验动物研究所

动物模型与实验医学(英文)

ISSN：2096-5451

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