Open AccessSonodynamic therapy reduces iron retention of hemorrhagic plaque
Author(s) -
Li Bicheng,
Gong Jie,
Sheng Siqi,
Lu Minqiao,
Guo Shuyuan,
Yao Jianting,
Zhang Haiyu,
Zhao Xuezhu,
Cao Zhengyu,
Sun Xin,
Wang Huan,
Cao Yang,
Jiang Yongxing,
Tian Zhen,
Liu Bin,
Zhao Hua,
Zhang Zhiguo,
Jin Hong,
Tian Ye
Publication year - 2021
Publication title -
bioengineering and translational medicine
Language(s) - English
Resource type - Journals
ISSN - 2380-6761
DOI - 10.1002/btm2.10193
Subject(s) - sonodynamic therapy , ferritin , foam cell , medicine , hepcidin , lesion , reactive oxygen species , apolipoprotein b , cancer research , inflammation , pathology , chemistry , lipoprotein , cholesterol , biochemistry , alternative medicine
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.