Sonodynamic therapy reduces iron retention of hemorrhagic plaque.

Abstract

Intraplaque hemorrhage (IPH) plays a major role in the aggressive progression of vulnerable plaque, leading to acute cardiovascular events. We previously demonstrated that sonodynamic therapy (SDT) inhibits atherosclerotic plaque progression. In this study, we investigated whether SDT could also be applied to treat more advanced hemorrhagic plaque and addressed the underlying mechanism. SDT decreased atherosclerotic burden, positively altered atherosclerotic lesion composition, and alleviated iron retention in rabbit hemorrhagic plaques. Furthermore, SDT reduced iron retention by stimulating ferroportin 1 (Fpn1) expression in apolipoprotein E (ApoE)-/- mouse plaques with high susceptibility to IPH. Subsequently, SDT inhibited iron-overload-induced foam-cell formation and pro-inflammatory cytokines secretion in vitro. Moreover, SDT reduced levels of the labile iron pool and ferritin expression via the reactive oxygen species (ROS)-nuclear factor erythroid 2-related factor 2 (Nrf2)-FPN1 pathway. SDT exerted therapeutic effects on hemorrhagic plaques and reduced iron retention via the ROS-Nrf2-FPN1 pathway in macrophages, thereby suggesting that it is a potential translational strategy for patients with advanced atherosclerosis in clinical practice.

• Authors: Bicheng Li, Jie Gong, Siqi Sheng, Minqiao Lu, Shuyuan Guo, Jianting Yao, Haiyu Zhang, Xuezhu Zhao, Zhengyu Cao, Xin Sun, Huan Wang, Yang Cao, Yongxing Jiang, Zhen Tian, Bin Liu, Hua Zhao, Zhiguo Zhang, Hong Jin, Ye Tian
• Journal: Bioengineering & translational medicine (Bioeng Transl Med) Vol. 6 Issue 1 Pg. e10193 (Jan 2021) ISSN: 2380-6761 [Print] United States
• PMID: 33532592 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.