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 Liqing WENG Tingting WU Xiaoguang WU Jiaming MIAO Xiasheng GUO Juan TU Dong ZHANG Bin ZHOU Wei SUN Xiangqing KONG
• 来源期刊: 浙江大学学报（英文版）（B辑：生物医学和生物技术）
• 年，卷（期）: 2021,（10）
• 所属期刊栏目: Research Articles
• 页码范围: 818-838,中插1-中插7
• 页数: 1页
• 语种: 英文

摘要

Objective:Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodel-ing induced by angiotensin Ⅱ(AngⅡ). Low-intensity pulsed ultrasound (LIPUS) has been reported to ameliorate cardiac dysfunc-tion 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.