The Role of Neutrophil Extracellular Traps in Atherosclerosis: From the Molecular to the Clinical Level

Yongfang Yuan,1 Changxin Sun,2 Xinyi Liu,2 Lanqing Hu,1 Zeping Wang,1 Xiaoya Li,1 Jingyi Zhang,2 Dexiu Li,1 Xiaonan Zhang,1 Min Wu,3 Longtao Liu1 1State Key Laboratory of Traditional Chinese Medicine Syndrome/National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, People’s Republic of China; 2Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Guang’an Men Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Xiaonan Zhang, Email [email protected] Longtao Liu, Email [email protected]: Atherosclerosis is a chronic inflammatory condition that is typified by the deposition of lipids and the subsequent inflammation of medium and large arteries. Neutrophil extracellular traps (NETs) are fibrous meshworks of DNA, histones, and granzymes expelled by activated neutrophils in response to a variety of pathogenic conditions. In addition to their role in pathogen eradication, NETs have been demonstrated to play a pivotal role in the development of atherosclerosis. This article presents a review of the bidirectional interactions in which atherosclerosis-related risk factors stimulate the formation of NETs, which in turn support disease progression. This article emphasizes the involvement of NETs in the various stages of atherogenesis and development, influencing multiple factors such as the vascular endothelium, platelets, the inflammatory milieu, and lipid metabolism. The findings of this study offer new insights and avenues for further investigation into the processes underlying the formation and regulation of the vascular inflammatory microenvironment in atherosclerosis. Finally, potential targeted therapeutic strategies for NETs are discussed to facilitate their progression to clinical practice (Graphical Abstract). Keywords: atherosclerosis, neutrophil traps, inflammation, lipid metabolism, therapeutic strategies