The beneficial pleiotropic effects of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) within the vasculature: A review of the evidence
The beneficial pleiotropic effects of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) within the vasculature: A review of the evidence
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DOI：
10.1016/j.atherosclerosis.2016.02.002
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发表时间：
2016-04-01
期刊：
影响因子：
5.3
通讯作者：
Cummins, Philip M.
中科院分区：
文献类型：
--
作者：
Forde, Hannah;Harper, Emma;Cummins, Philip M.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）是属于肿瘤坏死因子（TNF）细胞因子超家族的II型跨膜蛋白。TRAIL由许多细胞类型表达，包括血管细胞、免疫细胞和脂肪细胞。尽管最初认为仅在恶性或转化细胞中诱导凋亡，但现在已知TRAIL可以结合多达5种不同的受体以激活复杂的信号传导途径，并且能够在非转化细胞中发挥多效性作用。在这方面，许多临床和动物研究指出了TRAIL的潜在血管保护作用，其中TRAIL缺乏与加速的动脉粥样硬化和血管钙化有关。此外，外源性TRAIL给药已显示出体内抗动脉粥样硬化活性。然而，在这种情况下，对TRAIL的体外研究产生了相互矛盾的结果，有证据表明TRAIL具有促动脉粥样硬化和血管保护作用。尽管有这些不同的研究，关于血管系统内TRAIL介导的损伤/保护的确切性质以及TRAIL下游分子/细胞靶标的身份的机制信息仍然非常有限。在这篇综述中，我们将总结我们目前的知识，TRAIL的调节，信号传导机制，其明显参与CVD发病机制的前奏检查现有的证据TRAIL介导的血管保护。为此，将审查广泛的体外、体内和临床研究，并强调关键发现。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein that belongs to the tumour necrosis factor (TNF) cytokine superfamily. TRAIL is expressed by numerous cell types including vascular cells, immune cells and adipocytes. Although originally thought to induce apoptosis in malignant or transformed cells only, it is now known that TRAIL can bind up to 5 distinct receptors to activate complex signalling pathways, and is capable of exerting pleiotropic effects in non-transformed cells. In this respect, a number of clinical and animal studies point to the potential vasoprotective influence of TRAIL, with TRAIL deficiency being linked to accelerated atherosclerosis and vascular calcification. Moreover, exogenous TRAIL administration has been shown to exhibit anti-atherosclerotic activity in-vivo. In-vitro studies on TRAIL in this context have yielded conflicting results however, with evidence of both pro-atherogenic and vasoprotective effects ascribed to TRAIL. Notwithstanding these various studies, mechanistic information on the precise nature of TRAIL-mediated injury/protection within the vasculature, as well as the identity of the downstream molecular/cellular targets of TRAIL, is still quite limited. In this review, we will summarize our current knowledge of TRAIL regulation, signalling mechanisms, and its apparent involvement in CVD pathogenesis as a prelude to examining the existing evidence for TRAIL-mediated vasoprotection. To this end, extensive in vitro, in vivo, and clinical studies will be reviewed and critical findings highlighted. (C) 2016 Elsevier Ireland Ltd. All rights reserved.