Wu Han, Li Ran, Pei Li-Gang, Wei Zhong-Hai, Kang Li-Na, Wang Lian, Xie Jun, Xu Biao
Cell Physiol Biochem. 2018;47(4):1319-1337. doi: 10.1159/000490818. Epub 2018 Jun 19.
High mobility group box-1 (HMGB-1), a typical damage-associated molecular pattern protein released from various cells, was first identified in 1973. It is usually stored in the nuclei of cells. Several modifications of HMGB-1 promote its translocation to the cytosol, and it is actively or passively released from cells. When outside of the cells, HMGB-1is crucial in inflammation. It exerts its biological functions via interaction with its receptors, including receptor for advanced glycation end products (RAGE) and Toll-like receptor 4(TLR4). A large number of studies showed a close link between inflammation and thrombosis. This review demonstrated the increased expression of HMGB-1 in thrombosis-related diseases, including coronary artery disease, stroke, peripheral arterial disease, disseminated intravascular coagulation, and venous thrombosis. Besides, it summarized the current understanding of the emerging link between HMGB-1 and thrombosis from three aspects: platelet, NETs, and coagulation and fibrinolysis factors. Finally, it explored the possible therapeutic strategies targeting HMGB-1 for treating thrombosis-related diseases.
高迁移率族蛋白B1(HMGB-1)是一种从各种细胞中释放出来的典型的损伤相关分子模式蛋白,于1973年首次被鉴定出来。它通常储存在细胞核中。HMGB-1的几种修饰促进其向细胞质的转运,并使其从细胞中主动或被动释放。当在细胞外时,HMGB-1在炎症中起关键作用。它通过与其受体相互作用发挥生物学功能,包括晚期糖基化终产物受体(RAGE)和Toll样受体4(TLR4)。大量研究表明炎症与血栓形成之间存在密切联系。本综述展示了HMGB-1在血栓形成相关疾病中的表达增加,这些疾病包括冠状动脉疾病、中风、外周动脉疾病、弥散性血管内凝血和静脉血栓形成。此外,它从血小板、中性粒细胞胞外陷阱(NETs)以及凝血和纤溶因子三个方面总结了目前对HMGB-1与血栓形成之间新出现联系的理解。最后,它探讨了针对HMGB-1治疗血栓形成相关疾病的可能治疗策略。