UNC Blood Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, CT, United States.
Front Immunol. 2022 Nov 14;13:1039843. doi: 10.3389/fimmu.2022.1039843. eCollection 2022.
In the broad range of human diseases, thrombo-inflammation appears as a clinical manifestation. Clinically, it is well characterized in context of superficial thrombophlebitis that is recognized as thrombosis and inflammation of superficial veins. However, it is more hazardous when developed in the microvasculature of injured/inflamed/infected tissues and organs. Several diseases like sepsis and ischemia-reperfusion can cause formation of microvascular thrombosis subsequently leading to thrombo-inflammation. Thrombo-inflammation can also occur in cases of antiphospholipid syndrome, preeclampsia, sickle cell disease, bacterial and viral infection. One of the major contributors to thrombo-inflammation is the loss of normal anti-thrombotic and anti-inflammatory potential of the endothelial cells of vasculature. This manifest itself in the form of dysregulation of the coagulation pathway and complement system, pathologic platelet activation, and increased recruitment of leukocyte within the microvasculature. The role of platelets in hemostasis and formation of thrombi under pathologic and non-pathologic conditions is well established. Platelets are anucleate cells known for their essential role in primary hemostasis and the coagulation pathway. In recent years, studies provide strong evidence for the critical involvement of platelets in inflammatory processes like acute ischemic stroke, and viral infections like Coronavirus disease 2019 (COVID-19). This has encouraged the researchers to investigate the contribution of platelets in the pathology of various thrombo-inflammatory diseases. The inhibition of platelet surface receptors or their intracellular signaling which mediate initial platelet activation and adhesion might prove to be suitable targets in thrombo-inflammatory disorders. Thus, the present review summarizes the concept and mechanism of platelet signaling and briefly discuss their role in sterile and non-sterile thrombo-inflammation, with the emphasis on role of platelets in COVID-19 induced thrombo-inflammation. The aim of this review is to summarize the recent developments in deciphering the role of the platelets in thrombo-inflammation and discuss their potential as pharmaceutical targets.
在广泛的人类疾病中，血栓炎症表现为一种临床表现。临床上，它在浅表血栓性静脉炎中表现得非常明显，被认为是浅静脉的血栓形成和炎症。然而，当它在受伤/发炎/感染的组织和器官的微血管中发展时，情况就更危险了。一些疾病，如败血症和缺血再灌注，会导致微血管血栓形成，随后导致血栓炎症。抗磷脂综合征、子痫前期、镰状细胞病、细菌和病毒感染也会导致血栓炎症。血栓炎症的一个主要原因是血管内皮细胞正常的抗血栓和抗炎能力丧失。这表现为凝血途径和补体系统的失调、病理性血小板激活以及白细胞在微血管中的募集增加。血小板在止血和病理性和非病理性条件下血栓形成中的作用已经得到充分证实。血小板是无核细胞，以其在初级止血和凝血途径中的重要作用而闻名。近年来，研究为血小板在急性缺血性中风和冠状病毒病 2019 (COVID-19) 等炎症过程中的关键作用提供了强有力的证据。这促使研究人员研究血小板在各种血栓炎症性疾病中的病理作用。抑制血小板表面受体或介导初始血小板激活和黏附的细胞内信号可能被证明是血栓炎症性疾病的合适靶点。因此，本综述总结了血小板信号转导的概念和机制，并简要讨论了它们在无菌和非无菌血栓炎症中的作用，重点讨论了血小板在 COVID-19 诱导的血栓炎症中的作用。本综述的目的是总结近年来在揭示血小板在血栓炎症中的作用方面的最新进展，并讨论它们作为药物靶点的潜力。
