Abstract
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.
Highlights
Hemostasis is a physiological process of host defense that acts to stop bleeding in case of injury to keep the blood flow contained and under pressure
In 2014, Ho and colleagues [90] showed that sivelestat, a molecule acting on the early stages of NETosis through the inhibition of neutrophil elastase (NE), led to a significant decrease in tumor growth and progression
This review covers the different mice models of thrombosis used by the scientific community revealing the involvement of neutrophils and neutrophils extracellular traps (NETs) in thrombosis
Summary
Hemostasis is a physiological process of host defense that acts to stop bleeding in case of injury to keep the blood flow contained and under pressure. The mechanism proposed by the authors is that: (1) TFPI circulating and/or released by cellular actors, such as the endothelium and platelets, is recruited to the site of injury and (2) incorporated into the forming thrombus, where (3) its degradation by serine proteases from the neutrophils present can take place. Other models preserve the integrity of the endothelium and activate it This mechanism is present in human pathologies such as lower limb phlebitis and cancer-associated thrombosis, and in immunothrombotic diseases, including infections. The study of these numerous pathophysiological mechanisms allows the development of new therapeutic strategies to fight cardiovascular mortality worldwide
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