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  3. Iron deficiency anemia and platelet dysfunction: A comprehensive analysis of the underlying mechanisms

Iron deficiency anemia and platelet dysfunction: A comprehensive analysis of the underlying mechanisms

  • Life Sci. 2024 Aug 15:351:122848. doi: 10.1016/j.lfs.2024.122848.
Sijia Liu 1,  Fang Guo 1,  Tianli Zhang 1,  Ying Zhu 2,  Meng Lu 3,  Xiayu Wu 1,  Fuqin He 1,  Ruiying Yu 1,  Dan Yan 4,  Zhangyin Ming 5,  Dan Shu 6
Affiliations

Affiliations

  • 1 Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China; Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
  • 2 Wuhan No.1 Hospital, Wuhan 430071, China.
  • 3 Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
  • 4 Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China; Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China. Electronic address: yandan@wust.edu.cn.
  • 5 Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China. Electronic address: zyming@hust.edu.cn.
  • 6 Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China; Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China. Electronic address: shudan1024@wust.edu.cn.
PMID: 38885879 DOI: 10.1016/j.lfs.2024.122848
Abstract

Aims: This research aimed to study the changes in platelet function and their underlying mechanisms in iron deficiency anemia.

Main methods: Initially, we evaluated platelet function in an IDA mice model. Due to the inability to accurately reduce intracellular Fe2+ concentrations, we investigated the impact of Fe2+ on platelet function by introducing varying concentrations of Fe2+. To probe the underlying mechanism, we simultaneously examined the dynamics of calcium in the cytosol, and Integrin αIIbβ3 activation in Fe2+-treated platelets. Ferroptosis inhibitors Lip-1 and Fer-1 were applied to determine whether Ferroptosis was involved in this process.

Key findings: Our study revealed that platelet function was suppressed in IDA mice. Fe2+ concentration-dependently facilitated platelet activation and function in vitro. Mechanistically, Fe2+ promoted calcium mobilization, Integrin αIIbβ3 activation, and its downstream outside-in signaling. Additionally, we also demonstrated that Ferroptosis might play a role in this process.

Significance: Our data suggest an association between iron and platelet activation, with iron deficiency resulting in impaired platelet function, while high concentrations of Fe2+ contribute to platelet activation and function by promoting calcium mobilization, αIIbβ3 activation, and Ferroptosis.

Keywords

Calcium mobilization; Ferroptosis; Iron deficiency anemia; Platelets activation; αIIbβ3.

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