Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, Germany.
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) e.V., Partner Site Munich Heart Alliance, Munich, Germany.
Thromb Haemost. 2020 Nov;120(11):1492-1504. doi: 10.1055/s-0040-1714352. Epub 2020 Aug 9.
The pathogenesis of atherosclerotic vascular disease is driven by a multitude of risk factors intertwining metabolic and inflammatory pathways. Increasing knowledge about platelet biology sheds light on how platelets take part in these processes from early to later stages of plaque development. Recent insights from experimental studies and mouse models substantiate platelets as initiators and amplifiers in atherogenic leukocyte recruitment. These studies are complemented by results from genetics studies shedding light on novel molecular mechanisms which provide an interesting prospect as novel targets. For instance, experimental studies provide further details how platelet-decorated von Willebrand factor tethered to activated endothelial cells plays a role in atherogenic monocyte recruitment. Novel aspects of platelets as atherogenic inductors of neutrophil extracellular traps and particularities in signaling pathways such as cyclic guanosine monophosphate and the inhibitory adaptor molecule SHB23/LNK associating platelets with atherogenesis are shared. In summary, it was our intention to balance insights from recent experimental data that support a plausible role for platelets in atherogenesis against a paucity of clinical evidence needed to validate this concept in humans.
动脉粥样硬化性血管疾病的发病机制是由多种相互交织的代谢和炎症途径的风险因素驱动的。对血小板生物学的认识不断增加,揭示了血小板如何从斑块形成的早期到晚期参与这些过程。来自实验研究和小鼠模型的最新研究结果证实,血小板是动脉粥样硬化性白细胞募集的启动子和放大器。这些研究的结果还来自遗传学研究,揭示了新的分子机制,为新的靶点提供了有趣的前景。例如,实验研究进一步详细说明了血小板修饰的 von Willebrand 因子与激活的内皮细胞结合在动脉粥样硬化性单核细胞募集中的作用。血小板作为动脉粥样硬化性诱导中性粒细胞细胞外陷阱的诱导物的新方面,以及环鸟苷酸和抑制性衔接子分子 SHB23/LNK 等信号通路的特殊性,将血小板与动脉粥样硬化联系起来,这些都是共同的。总之,我们的目的是平衡支持血小板在动脉粥样硬化发病机制中发挥作用的最新实验数据的见解,以及在人类中验证这一概念所需的临床证据的缺乏。