Intertwining of thrombosis and inflammation in atherosclerosis
Intertwining of thrombosis and inflammation in atherosclerosis
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DOI：
10.1097/00062752-200701000-00011
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Libby, Peter
中科院分区：
文献类型：
--
作者：
Croce, Kevin;Libby, Peter
本文的目的是强调血栓形成过程在动脉粥样硬化性血管疾病的发展和并发症中的重要性。血管炎症部位产生的凝血酶可激活主要的动脉粥样硬化相关细胞，包括内皮细胞、血小板、平滑肌细胞、单核细胞和巨噬细胞。凝血酶激活的细胞产生过多的炎症介质，如经活化调节的正常T细胞表达的推定分泌、巨噬细胞迁移抑制因子和CD40配体，促进动脉粥样硬化病变形成和血管疾病的动脉粥样硬化血栓并发症。此外，凝血酶诱导的炎症介质刺激动脉粥样硬化内的组织因子促凝活性，启动一个正反馈循环，其中凝血酶激活发出炎症信号，导致凝血酶进一步激活。血小板是血栓形成系统的主要细胞效应物，在动脉粥样硬化的生物学过程中也发挥着核心作用，它产生炎症介质，并通过血小板介导的白细胞粘附引导白细胞并入斑块。新的研究已经确定了与动脉粥样硬化的发展和进展相互交织的血栓形成和炎症途径的信号通路。这些信号通路包含促进动脉粥样硬化形成的正反馈回路。同时靶向血栓和炎症界面的分子调节因子可能会减少血栓和炎症，从而打破促进动脉粥样硬化和相关血栓并发症的病理循环。
Purpose of review The aim of this article is to highlight the importance of thrombotic processes in the development and complications of atherosclerotic vascular disease.Recent findings Thrombin generated at sites of vascular inflammation activates major atheroma-associated cells including endothelial cells, platelets, smooth muscle cells, monocytes, and macrophages. Thrombin-activated cells produce a plethora of inflammatory mediators, such as regulated upon activation normal T cell expressed presumed secreted, macrophage migration inhibitory factor, and CD40 ligand, that promote atherosclerotic lesion formation and atherothrombotic complications of vascular disease. Additionally, thrombin-induced inflammatory mediators stimulate tissue factor procoagulant activity within atheroma to initiate a positive feedback loop where thrombin activation launches inflammatory signals that lead to further thrombin activation. Platelets, the main cellular effectors of the thrombotic system, also play a central role in the biology of atherosclerosis by producing inflammatory mediators and directing leukocyte incorporation into plaques through platelet-mediated leukocyte adhesion.Summary New research has identified signaling pathways that intertwine thrombotic and inflammatory pathways with the development and progression of atherosclerosis. These signaling pathways contain positive feedback loops that propagate atherogenesis. Targeting molecular regulators at the interface of thrombosis and inflammation simultaneously may reduce thrombosis and inflammation, thus breaking pathological cycles that promote atherosclerosis and associated thrombotic complications.