Yu Fei, Chen Jianshu, Zhang Xiaowei, Ma Zhengke, Wang Jingtao, Wu Qiang
Department of Cardiovascular Medicine, Lanzhou University Second Hospital, Lanzhou, China.
J Clin Hypertens (Greenwich). 2025 Jan;27(1):e14942. doi: 10.1111/jch.14942. Epub 2024 Dec 17.
Hypertension is the predominant cause of cardiovascular diseases (CVDs) globally, and essential hypertension (EH) represents a significant public health challenge due to its multifactorial etiology involving complex interactions between genetic and environmental factors. However, the pathogenesis of EH is still unclear. Hypertension is a dysregulation in the renin-angiotensin-aldosterone system and sympathetic nervous system, both regulating saline homeostasis and cardiovascular function. However, current therapeutic interventions targeting these systems have limited efficacy in approximately 40% of cases, suggesting the involvement of alternative mechanisms. Inflammation is associated with the occurrence and progression of hypertension, but the underlying mechanism remains elusive, while chronic inflammation leads to tissue damage, fibrosis, and irreversible organ dysfunction. The development and maintenance of EH are caused by endothelial dysfunction, oxidative stress, and chronic inflammation. Neutrophils are involved in both acute and chronic inflammation since they represent the primary line of defense against inflammatory insults once recruited to the inflamed site where they remove harmful impurities. The process involving the formation of neutrophil extracellular traps (NETs) is called NETosis are involved in the pathogenesis and progression of CVDs, including coronary artery disease, acute myocardial infarction, peripheral arterial disease, heart failure, and atrial fibrillation. Recent investigations demonstrated that NETs facilitate the development of hypertension; however, the precise role of NETs in hypertension remains largely elusive. Therefore, this review aims to provide an overview of the current understanding regarding the involvement of NETosis in hypertension and explore the potential therapies targeting NETs for future interventions.
高血压是全球心血管疾病（CVDs）的主要病因，原发性高血压（EH）因其多因素病因涉及遗传和环境因素之间的复杂相互作用，构成了重大的公共卫生挑战。然而，EH的发病机制仍不清楚。高血压是肾素-血管紧张素-醛固酮系统和交感神经系统的失调，这两个系统都调节盐平衡和心血管功能。然而，目前针对这些系统的治疗干预措施在大约40%的病例中疗效有限，这表明存在其他机制。炎症与高血压的发生和发展有关，但其潜在机制仍不清楚，而慢性炎症会导致组织损伤、纤维化和不可逆的器官功能障碍。EH的发生和维持是由内皮功能障碍、氧化应激和慢性炎症引起的。中性粒细胞参与急性和慢性炎症，因为它们一旦被招募到炎症部位，就代表了抵御炎症损伤的第一道防线，在那里它们清除有害杂质。涉及中性粒细胞胞外陷阱（NETs）形成的过程称为NETosis，它参与了包括冠状动脉疾病、急性心肌梗死、外周动脉疾病、心力衰竭和心房颤动在内的心血管疾病的发病机制和进展。最近的研究表明，NETs促进了高血压的发展；然而，NETs在高血压中的确切作用在很大程度上仍不清楚。因此，本综述旨在概述目前对NETosis参与高血压的理解，并探索针对NETs的潜在治疗方法以供未来干预。
