Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy.
Department of Internal Medicine, First Clinic of Internal Medicine, Ospedale Policlinico San Martino, 10 Largo Benzi, Genoa, Italy.
J Cell Physiol. 2019 Mar;234(3):2121-2133. doi: 10.1002/jcp.27575. Epub 2018 Oct 14.
Although coronary thrombosis (CT) is integral to cardiovascular outcomes, the underlying pathophysiological mechanisms remain unclear. CT may occur in case of atherosclerotic plaque erosion/rupture, or even after stenting implantation. Platelets (PLT) activation is the keystone of atherothrombosis and depends on many dysregulated elements, including endothelial dysfunction, oxidized lipoproteins, and immune response. Besides the classical view of PLT as an effector of hemostatic response, a new repertoire of PLT activities is emerging. PLT lipidome oxidation is a self-maintaining process which promotes PLT reactivity, coagulation cascade, and inflammatory cell activation. PLT-innate immune cell interaction is also sustained by neutrophil extracellular traps and NLRP3 inflammasome pathways. Other noteworthy emerging mechanisms are implicated in the crosstalk between PLT and surrounding cells. Especially, microvesicles (MVs) released from PLT may extend their signaling network far beyond the classical cell-cell interactions. Moreover, the recognition of noncoding RNA in PLT MVs introduce another layer of complexity in terms of intercellular signaling by a direct regulation of messenger RNA profile and gene expression in the recipient cells. The aim of this narrative review is to update the recent advance in CT and intracoronary stent thrombosis, including causal factors and potential translation of experimental evidence into the clinical setting.
虽然冠状动脉血栓形成（CT）是心血管结局的重要组成部分，但潜在的病理生理机制仍不清楚。CT 可能发生在动脉粥样硬化斑块侵蚀/破裂的情况下，甚至在支架植入后也可能发生。血小板（PLT）的激活是动脉血栓形成的关键，取决于许多失调的因素，包括内皮功能障碍、氧化脂蛋白和免疫反应。除了将 PLT 视为止血反应的效应器的经典观点外，PLT 的新作用正在出现。PLT 脂质体氧化是一个自我维持的过程，它促进 PLT 反应性、凝血级联和炎症细胞激活。PLT-先天免疫细胞的相互作用也受到中性粒细胞细胞外陷阱和 NLRP3 炎性小体途径的维持。其他值得注意的新兴机制涉及 PLT 与周围细胞之间的串扰。特别是，从 PLT 释放的微小泡（MVs）可能会将其信号网络扩展到经典的细胞-细胞相互作用之外。此外，PLT MVs 中的非编码 RNA 的识别为细胞间信号传导引入了另一个层面的复杂性，通过直接调节信使 RNA 谱和受体细胞中的基因表达来实现。本叙述性综述的目的是更新 CT 和冠状动脉内支架血栓形成的最新进展，包括因果因素和将实验证据潜在转化为临床环境。
