Kun Zhao1, Jing Zhang1, Tianhua Xu1, Chuanxi Yang1, Liqing Weng1, Tingting Wu1, Xiaoguang Wu1, Jiaming Miao2, Xiasheng Guo2, Juan Tu2, Dong Zhang2, Bin Zhou3,4, Wei Sun5, Xiangqing Kong1. 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. Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. bin.zhou@einstein.yu.edu. 4. Departments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA. bin.zhou@einstein.yu.edu. 5. Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. weisun7919@njmu.edu.cn.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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.
Authors: Elizabeth R Vogel; Logan J Manlove; Ine Kuipers; Michael A Thompson; Yun-Hua Fang; Michelle R Freeman; Rodney D Britt; Arij Faksh; Binxia Yang; Y S Prakash; Christina M Pabelick Journal: Am J Physiol Lung Cell Mol Physiol Date: 2019-05-01 Impact factor: 5.464
Authors: Dimitrios Grivas; Álvaro González-Rajal; Carlos Guerrero Rodríguez; Ricardo Garcia; José Luis de la Pompa Journal: Sci Rep Date: 2020-07-30 Impact factor: 4.379