4.6 Article

Memory-like response in platelet attenuates platelet hyperactivation in arterial thrombosis

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.04.018

Keywords

Platelets; Thrombosis; Memory-like response; Lipopolysaccharide; PI3K

Funding

  1. National Natural Science Foundation of China [81973580, 81803866]
  2. COVID-19 Science and Technology Emergency Project of Sichuan Province of China [2021YFS0408]
  3. Key Technology Research and Development Program of Sichuan Province of China [2022YFS0425, 2022YFS0426]
  4. Sichuan University [HXYS19001, HXYS19002, ZYXY21002, 161200012]

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Recent studies have shown that platelets may exhibit memory-like responses to pathogen stimulation, which can be mediated by the PI3K/AKT signaling pathway and mitochondrial DNA methylation. These memory-like responses in platelets contribute to immune responses and play a protective role in arterial thrombosis.
Recent studies showed that in responding of pathogens stimulation, immune cells and other cells display memory-like effects. Platelets are primary effectors of hemostasis and thrombosis which also participate in immune responses. However, there is no relevant research on whether memory-like effect exists in platelets. In our study after recovery from repetitive LPS stimulus, platelets aggregation, diffusion and clot retraction exhibit a significant reduction. It proves that memory-like response could be aroused in platelets. Furthermore, in the mouse arterial thrombosis model, LPS pretreated platelets showed lower integrin activation, shorter thrombus length and longer occlusion time, indicating that the memory-like response of platelet could alleviate arterial thrombosis. Moreover, memory-like response of platelets was also found to be related to PI3K/AKT signaling pathway. The decreased mitochondrial DNA methylation reveal that platelet memory-like responses may be produced from epigenetic reprogramming. Our research proves for the first time that memory-like response in platelets protects mice from arterial thrombosis, extends the understanding of trained memory.(c) 2022 Elsevier Inc. All rights reserved.

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