Low‐intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway  

作　　者：Kun ZHAO Jing ZHANG Tianhua XU Chuanxi YANG LiqingWENG TingtingWU XiaoguangWU Jiaming MIAO Xiasheng GUO Juan TU Dong ZHANG Bin ZHOU Wei SUN Xiangqing KONG 

机构地区：[1]Department of Cardiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China [2]Key Laboratory of Modern Acoustics,Department of Physics,Collaborative Innovation Center of Advanced Microstructure,Nanjing University,Nanjing 210093,China [3]Departments of Genetics,Pediatrics,and Medicine(Cardiology),Wilf Cardiovascular Research Institute,Albert Einstein College of Medicine,Bronx,NY 10461,USA

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2021年第10期818-838,共21页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：This work was supported by the National Natural Science Foundation of China(No.81627802);the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.PAPD2014-2016);the National Key R&D Program of China(No.2019YFA0210100).

摘　　要：Objective:Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II(AngII).Low-intensity pulsed ultrasound(LIPUS)has been reported to ameliorate cardiac dysfunction and myocardial fibrosis in myocardial infarction(MI)through mechano-transduction and its downstream pathways.In this study,we aimed to investigate whether LIPUS could exert a protective effect by ameliorating AngII-induced cardiac hypertrophy and fibrosis and if so,to further elucidate the underlying molecular mechanisms.Methods:We used AngII to mimic animal and cell culture models of cardiac hypertrophy and fibrosis.LIPUS irradiation was applied in vivo for 20 min every 2 d from one week before mini-pump implantation to four weeks after mini-pump implantation,and in vitro for 20 min on each of two occasions 6 h apart.Cardiac hypertrophy and fibrosis levels were then evaluated by echocardiographic,histopathological,and molecular biological methods.Results:Our results showed that LIPUS could ameliorate left ventricular remodeling in vivo and cardiac fibrosis in vitro by reducing AngII-induced release of inflammatory cytokines,but the protective effects on cardiac hypertrophy were limited in vitro.Given that LIPUS increased the expression of caveolin-1 in response to mechanical stimulation,we inhibited caveolin-1 activity with pyrazolopyrimidine 2(pp2)in vivo and in vitro.LIPUS-induced downregulation of inflammation was reversed and the anti-fibrotic effects of LIPUS were absent.Conclusions:These results indicated that LIPUS could ameliorate AngII-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway,providing new insights for the development of novel therapeutic apparatus in clinical practice.

关 键 词：Low-intensity pulsed ultrasound(LIPUS) CAVEOLIN-1 Cardiac fibrosis INFLAMMATION Angiotensin II(AngII) 

分 类 号：R542.22[医药卫生—心血管疾病]