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

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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)818-838
Number of pages21
JournalJournal of Zhejiang University: Science B
Issue number10
StatePublished - Oct 2021


  • Angiotensin II (AngII)
  • Cardiac fibrosis
  • Caveolin-1
  • Inflammation
  • Low-intensity pulsed ultrasound (LIPUS)

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology
  • General Veterinary


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