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Research progress on the impact and mechanism of neutrophil extracellular traps (NETs) components in atherosclerosis

CHEN Xin¹, ZHU Jing-Jing¹, YANG Xiao-Fan^1,2, MA Yu-Peng^1,2, BAO Yi-Min¹, NING Ke^2,*

¹School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China；²School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Abstract

Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.

Key words: Atherosclerosis; neutrophil extracellular traps; histone; myeloperoxidase; cathepsin G; neutrophil elastase; matrix metalloproteinases; antimicrobial peptide LL-37; alpha-defensin 1-3; high mobility group protein B1

Received: 　　Accepted:

Corresponding author: 宁可　　E-mail:

DOI: 10.13294/j.aps.2025.0013

Citing This Article：

CHEN Xin, ZHU Jing-Jing, YANG Xiao-Fan, MA Yu-Peng, BAO Yi-Min, NING Ke. Research progress on the impact and mechanism of neutrophil extracellular traps (NETs) components in atherosclerosis. Acta Physiol Sin 2025; 77 (1): 107-119 (in Chinese with English abstract).