1. Academic Validation
  2. A Membrane-Targeting Aggregation-Induced Emission Probe for Monitoring Lipid Droplet Dynamics in Ischemia/Reperfusion-Induced Cardiomyocyte Ferroptosis

A Membrane-Targeting Aggregation-Induced Emission Probe for Monitoring Lipid Droplet Dynamics in Ischemia/Reperfusion-Induced Cardiomyocyte Ferroptosis

  • Adv Sci (Weinh). 2024 May 2:e2309907. doi: 10.1002/advs.202309907.
Yihui Wang 1 2 3 Yuan Song 1 2 3 Lingling Xu 1 2 3 Wuqi Zhou 1 2 3 Wenyuan Wang 1 2 3 Qiaofeng Jin 1 2 3 Yuji Xie 1 2 3 Junmin Zhang 1 2 3 Jing Liu 1 2 3 Wenqian Wu 1 2 3 He Li 1 2 3 Le Liang 4 Jing Wang 1 2 3 Yali Yang 1 2 3 Xiongwen Chen 5 6 Shuping Ge 7 Tang Gao 1 2 3 Li Zhang 1 2 3 8 Mingxing Xie 1 2 3 8
Affiliations

Affiliations

  • 1 Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Clinical Research Center for Medical Imaging, No. 1277 Jiefang Avenue, Wuhan, Hubei, 430022, China.
  • 3 Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
  • 4 The Institute of Advanced Studies Wuhan University, Wuhan, 430072, China.
  • 5 Department of Biopharmaceuticals & Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300052, China.
  • 6 Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, 300052, China.
  • 7 Drexel University College of Medicine and St. Christopher's Hospital for Children, 3601 A Street, Philadelphia, PA, 19134, USA.
  • 8 Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518029, China.
Abstract

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)-induced cardiomyocyte Ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R-induced cardiomyocyte Ferroptosis is unclear. In this study, an aggregation-induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R-induced Ferroptosis. TPABTBP exhibits excellent LD-specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super-resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0-9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA-approved Autophagy modulator, can inhibit Ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.

Keywords

aggregation‐induced emissions; ferroptosis; lipid droplet imaging; lipophagy; myocardial ischemia/reperfusion injury.

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