Aix Marseille Univ, INSERM 1263 (Institut National de la Santé et de la Recherche), INRAE 1260 (Institut National de la Recherche Agronomique et de l'Environnement), C2VN (Center for CardioVascular and Nutrition Research), 13885 Marseille, France.
Aix Marseille University, PIVMI (Plateforme d'Imagerie Vasculaire et de Microscopie Intravitale), C2VN (Center for CardioVascular and Nutrition Research), 13385 Marseille, France.
Int J Mol Sci. 2022 Jan 26;23(3):1411. doi: 10.3390/ijms23031411.
Thrombosis is one of the major causes of mortality worldwide. Notably, it is not only implicated in cardiovascular diseases, such as myocardial infarction (MI), stroke, and pulmonary embolism (PE), but also in cancers. Understanding the cellular and molecular mechanisms involved in platelet thrombus formation is a major challenge for scientists today. For this purpose, new imaging technologies (such as confocal intravital microscopy, electron microscopy, holotomography, etc.) coupled with animal models of thrombosis (mouse, rat, rabbit, etc.) allow a better overview of this complex physiopathological process. Each of the cellular components is known to participate, including the subendothelial matrix, the endothelium, platelets, circulating cells, and, notably, neutrophils. Initially known as immune cells, neutrophils have been considered to be part of the landscape of thrombosis for more than a decade. They participate in this biological process through their expression of tissue factor (TF) and protein disulfide isomerase (PDI). Moreover, highly activated neutrophils are described as being able to release their DNA and thus form chromatin networks known as "neutrophil extracellular traps" (NETs). Initially, described as "dead sacrifices for a good cause" that prevent the dissemination of bacteria in the body, NETs have also been studied in several human pathologies, such as cardiovascular and respiratory diseases. Many articles suggest that they are involved in platelet thrombus formation and the activation of the coagulation cascade. This review presents the models of thrombosis in which neutrophils and NETs are involved and describes their mechanisms of action. We have even highlighted the medical diagnostic advances related to this research.
血栓形成是全球主要死亡原因之一。值得注意的是,它不仅与心血管疾病(如心肌梗死 (MI)、中风和肺栓塞 (PE))有关,还与癌症有关。了解血小板血栓形成涉及的细胞和分子机制是当今科学家面临的主要挑战。为此,新的成像技术(如共聚焦活体显微镜、电子显微镜、全层析成像等)与血栓形成的动物模型(小鼠、大鼠、兔子等)相结合,使人们能够更好地了解这一复杂的生理病理过程。已知每个细胞成分都参与其中,包括内皮下基质、内皮细胞、血小板、循环细胞,特别是中性粒细胞。中性粒细胞最初被认为是免疫细胞,十多年来一直被认为是血栓形成景观的一部分。它们通过表达组织因子 (TF) 和蛋白二硫键异构酶 (PDI) 参与这一生物学过程。此外,高度激活的中性粒细胞被描述为能够释放其 DNA,从而形成称为“中性粒细胞胞外陷阱”(NETs)的染色质网络。最初,NETs 被描述为“为了一个好的目的而牺牲的死亡细胞”,可以防止细菌在体内传播,在心血管和呼吸等几种人类疾病中也对其进行了研究。许多文章表明,它们参与了血小板血栓形成和凝血级联的激活。这篇综述介绍了涉及中性粒细胞和 NETs 的血栓形成模型,并描述了它们的作用机制。我们甚至强调了与该研究相关的医学诊断进展。