A murine model of aortic regurgitation generated by transapical wire destruction of the aortic valve  

作  者:Xiaoxia Huang Qiancheng Wang Dan Han Hairuo Lin Zhihong Li Cankun Zheng Jianping Bin Wangjun Liao Zhanchun Cong Mengjia Shen Yulin Liao 

机构地区:[1]Cardiovascular Center,The Sixth Affiliated Hospital,School of Medicine,South China University of Technology,Foshan,China [2]Department of Cardiology,State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Lab of Cardiac Function and Microcirculation,Nanfang Hospital,Southern Medical University,Guangzhou,China [3]Foshan Key Laboratory of Translational Medicine in Oncology,Cancer Center,The Sixth Affiliated Hospital,School of Medicine,South China University of Technology,Foshan,China

出  处:《Animal Models and Experimental Medicine》2025年第3期493-500,共8页动物模型与实验医学(英文)

基  金:Natural Science Foundation of Guangdong Province,Grant/Award Number:2023A1515110032 and 2022A1515220152;Guangzhou Key Research and Development Program Foundation,Grant/Award Number:202206010199;National Natural Science Foundation of China,Grant/Award Number:82100407,82272602 and 82370242。

摘  要:Background:The mechanisms underlying cardiac remodeling in aortic valvular(AoV)disease remain poorly understood,partially due to the insufficiency of appropriate preclinical animal models.Here,we present a novel murine model of aortic regurgitation(AR)generated by transapical wire destruction of the AoV.Methods:Directed by echocardiography,apical puncture of the left ventricle(LV)was performed in adult male C57BL/6 mice,and a metal guidewire was used to induce AoV destruction.Echocardiography,invasive LV hemodynamic and histological examination were conducted to assess the degree of AR,LV function and remodeling.Results:AR mice exhibited rapid aortic regurgitation velocity(424±15.22 mm/s)immediately following successful surgery.Four weeks post-surgery,echocardiography revealed a 54.6%increase in LV diastolic diameter and a 55.1%decrease in LV ejection fraction in AR mice compared to sham mice.Pressure-volume catheterization indicated that AR mice had significantly larger LV end-diastolic volumes(66.2±1.5μL vs.41.8±3.4μL),reduced LV contractility(lower dP/dt max and Ees),and diminished LV compliance(smaller dP/dt min and longer Tau)compared to sham mice.Histological examination demonstrated that AR mice had significantly larger cardiomyocyte area and more myocardial fibrosis in LV tissue,as well as a 107%and a 122%increase of heart weight/tibial length and lung weight/tibial length,respectively,relative to sham mice.Conclusions:The trans-apex wire-induced destruction of the AoV establishes a novel and efficient murine model to develop AR,characterized by significant eccentric LV hypertrophy,heart failure,and pulmonary congestion.

关 键 词:animal model aortic regurgitation eccentric hypertrophy heart failure volume overload 

分 类 号:R54[医药卫生—心血管疾病]

 

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