Low-intensity pulsed ultrasound prevents angiotensin II-induced aortic smooth muscle cell phenotypic switch via hampering miR-17-5p and enhancing PPAR-γ.

Kun Zhao, Tingting Wu, Chuanxi Yang, Haotian Pan, Tianhua Xu, Jing Zhang, Xiasheng Guo, Juan Tu, Dong Zhang, Xiangqing Kong, Bin Zhou, Wei Sun

European journal of pharmacology 2021 Nov 15

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Vascular events can trigger a pathological phenotypic switch in vascular smooth muscle cells (VSMCs), decreasing and disrupting the plasticity and diversity of vascular networks. The development of novel therapeutic approaches is necessary to prevent these changes. We aimed to investigate the effects and associated mechanisms of low-intensity pulsed ultrasound (LIPUS) irradiation on the angiotensin II (AngII)-induced phenotypic switch in VSMCs. In vivo, AngII was infused subcutaneously for 4 weeks to stimulate vascular remodeling in mice, and LIPUS irradiation was applied for 20 min every 2 days for 4 weeks. In vitro, cultured rat aortic VSMCs (RAVSMCs) were pretreated once with LIPUS irradiation for 20 min before 48-h AngII stimulation. Our results showed that LIPUS irradiation prevents AngII-induced vascular remodeling of the whole wall artery without discriminating between adventitia and media in vivo and RAVSMC phenotypic switching in vitro. LIPUS irradiation downregulated miR-17-5p expression and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression. The PPAR-γ activator rosiglitazone could mimic the favorable effects of LIPUS irradiation on AngII-treated RAVSMCs. In contrast, GW9662 could impede the LIPUS-mediated downregulation of RAVSMC proliferation and inflammation under AngII stimulation conditions in vivo and in vitro. Also, the miR-17-5p agomir has the same effects as GW9662 in vitro. Besides, the inhibitory effects of GW9662 against the anti-remodeling effects of LIPUS irradiation in AngII-induced RAVSMCs could be blocked by pretreatment with the miR-17-5p antagomir. Overall, LIPUS irradiation prevents AngII-induced RAVSMCs phenotypic switching through hampering miR-17-5p and enhancing PPAR-γ, suggesting a new approach for the treatment of vascular disorders. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Kun Zhao, Tingting Wu, Chuanxi Yang, Haotian Pan, Tianhua Xu, Jing Zhang, Xiasheng Guo, Juan Tu, Dong Zhang, Xiangqing Kong, Bin Zhou, Wei Sun. Low-intensity pulsed ultrasound prevents angiotensin II-induced aortic smooth muscle cell phenotypic switch via hampering miR-17-5p and enhancing PPAR-γ. European journal of pharmacology. 2021 Nov 15;911:174509