Low-Intensity Pulsed Ultrasound Prevents the Oxidative Stress Induced Endothelial-Mesenchymal Transition in Human Aortic Endothelial Cells

• Main Authors: Jiamin Li, Qingwei Zhang, Cong Ren, Xianxian Wu, Ying Zhang, Xue Bai, Yuan Lin, Mingqi Li, Jiangbo Fu, Philipp Kopylov, Siqi Wang, Tingting Yu, Ning Wang, Chaoqian Xu, Yong Zhang, Baofeng Yang
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2018-02-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Lipus; Migration; EndMT; Endothelial cell damage
• Online Access: https://www.karger.com/Article/FullText/487561
• ISSN: 1015-8987; 1421-9778

Background/Aims: Endothelial-mesenchymal transition (EndMT) has been shown to take part in the generation and progression of diverse diseases, involving a series of changes leading to a loss of their endothelial characteristics and an acquirement of properties typical of mesenchymal cells. Low-intensity pulsed ultrasound (LIPUS) is a new therapeutic option that has been successfully used in fracture healing. However, whether LIPUS can inhibit oxidative stress-induced endothelial cell damages through inhibiting EndMT remained unknown. This study aimed to investigate the protective effects of LIPUS against oxidative stress-induced endothelial cell damages and the underlying mechanisms. Methods: EndMT was induced by H2O2 (100 µm for seven days). Human aortic endothelial cells (HAECs) were exposed to H2O2 with or without LIPUS treatment for seven days. The expression of EndMT markers (CD31, VE-cadherin, FSP1 and α-SMA) were analyzed. The levels of total and phosphorylated PI3K and AKT proteins were detected by Western Blot analysis. Cell chemotaxis was determined by wound healing and transwell assay. Results: LIPUS relieved EndMT by decreasing ROS accumulation and increasing activation of the PI3K signaling cascade. LIPUS alleviated the migration of EndMT-derived mesenchymal-like cells through reducing extracellular matrix (ECM) deposition that is associated with matrix metallopeptidase (MMP) proteolytic activity and collagen production. Conclusion: LIPUS produces cytoprotective effects against oxidative injuries to endothelial cells through suppressing the oxidative stress-induced EndMT, activating the PI3K/AKT pathway under oxidative stress, and limiting cell migration and excessive ECM deposition.