Tumor necrosis factor superfamily molecules in acute coronary syndromes
Tumor necrosis factor superfamily molecules in acute coronary syndromes
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DOI：
10.3109/07853890.2010.523711
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发表时间：
2011-03-01
影响因子：
4.4
通讯作者：
Ueland, Thor
中科院分区：
文献类型：
--
作者：
Aukrust, Pal;Sandberg, Wiggo J.;Ueland, Thor
越来越多的证据表明，炎症通路在动脉粥样硬化形成的各个阶段都起着重要作用。炎症过程不仅参与斑块进展，而且似乎在斑块破裂中也起关键作用。肿瘤坏死因子（TNF）超家族成员是炎症和细胞存活的有效调节剂，由20种配体组成，通过29种不同的受体发出信号。一些证据表明TNF相关分子参与了急性冠状动脉综合征（ACS）的发展。大多数令人信服的证据表明CD 40配体-CD 40相互作用，但TNF超家族的其他几个成员似乎也参与了这种免疫介导的斑块不稳定性的促进，包括LIGHT，核因子的受体激活剂。B配体和TNF-α。这些斑块不稳定途径涉及血小板和内皮细胞/单核细胞之间的双向相互作用、血管平滑肌细胞的活化和对T细胞的共刺激作用，促进炎症、血栓形成、基质降解和细胞凋亡。肿瘤坏死因子相关通路可能导致动脉粥样硬化的非消退性炎症，代表斑块破裂和ACS发展过程中的致病循环。这些肿瘤坏死因子相关分子也可能成为治疗这种疾病的有吸引力的新靶点。
Accumulating evidence suggests that inflammatory pathways play an essential role in all stages of atherogenesis. Inflammatory processes are not only involved in plaque progression, but seem also to play a critical role in plaque rupture. Members of the tumor necrosis factor (TNF) superfamiliy are potent regulators of inflammation and cell survival and consist of 20 ligands that signal through 29 different receptors. Several lines of evidence suggest that TNF-related molecules are involved in the development of acute coronary syndromes (ACS). Most, convincing evidence exists for CD40 ligand-CD40 interaction, but several other members of the TNF superfamily seem also to be involved in this immune-mediated promotion of plaque instability, including LIGHT, receptor activator of nuclear factor. B ligand, and TNF-alpha. These plaque destabilization pathways involve the bidirectional interaction between platelets and endothelial cells/monocytes, activation of vascular smooth muscle cells, and co-stimulatory effects on T cells, promoting inflammation, thrombus formation, matrix degradation, and apoptosis. TNF-related pathways could contribute to the non-resolving inflammation that characterizes atherosclerosis, representing pathogenic loops that are operating during plaque rupture and the development of ACS. These TNF-related molecules could also represent attractive new targets for therapy in this disorder.