动脉粥样硬化血栓形成中的血小板突触分子

Platelet Synaptic Molecules in Atherosclerosis

动脉粥样硬化血栓性疾病的特征是动脉粥样硬化脂质斑块的破裂和血栓形成,血小板活化和聚集对这一疾病的病理生理和临床表现起重要作用。血栓形成过程中血小板之间也形成类似神经突触或免疫突触的突触性结构,即血小板突触(p latelet synapse),在此微环境中进行着血小板间的信号传递,称为血小板接触依赖性事件(contact-dependent events),对动脉血栓的形成和稳定起重要作用。在参与这一过程的血小板突触分子中,轴突导向分子(如Ephrins和Sem aphorins)开始引起人们的关注。除轴突生长导向作用外,轴突导向分子已证明在免疫应答、肿瘤转移、血管新生、血栓形成等病理生理过程中发挥作用。更为重要的是其中某些分子(如Sem a4D)的敲除可降低血脂异常状态下的血小板的高反应性,延缓动脉粥样硬化斑块的发展。本文将回顾近十年来对此类分子在动脉粥样硬化血栓形成中作用机制的研究进展。

The features of atherothrombotic diseases are the rupture of atherosclerotic plaques and thrombosis.Platelet activation and aggregation play a pivotal role in the pathogenesis and clinical manifestation.Similar to neuronal and immunological synapse,synaptic structure is also formed between platelets during thrombus formation.The microenvironment of platelet synapse facilitates signal transduction that has been accepted as contact-dependent events due to their occurrence after platelet contact begins,which is believed to play a role in the thrombus formation and stability.Axonal guidance molecules（eg Ephrins and Semaphorins） have been found in platlet synapse.In addition to axonal guidance,axonal guidance molecules have been shown to participate in the pathophysiological processes,including immune response,tumor metastasis,angiogenesis,and thrombosis. Most recently,it was found that deletion of a semaphorin family member,Sema4D,attenuated platelet hyperreactivity in the setting of dyslipidemia and protected from the development of atherosclerotic plaques.This article summarizes the progress in the understanding of the molecular mechanisms by which axonal guidance molecules affect atherothrombosis.