Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.
Minerva Med. 2012 Dec;103(6):513-24.
There is an ongoing search for biomarkers that can facilitate the diagnosis of subclinical or clinically manifest cardiovascular disease. One of the emerging biomarkers currently under investigation is ST2, which is the receptor of Interleukin-33 (IL-33). ST2 is a member of the Interleukin-1 receptor family and exists in a transmembrane (ST2L) and a soluble form (sST2) due to alternative splicing. Several groups have reported sST2 elevations in serum of cardiovascular disease patients. There is consisting evidence that sST2 is independently predictive for mortality in patients with heart failure or myocardial infarction. In addition to its potential as a biomarker for adverse cardiovascular events, ST2 is considered to play a causal role in chronic cardiovascular diseases such as atherosclerosis and heart failure. Signaling of IL-33 via ST2 has been shown to be cardioprotective in mouse models of myocardial infarction, heart transplantation and cardiac hypertrophy and fibrosis. Furthermore, treatment with IL-33 reduced the development of plaques in atherosclerotic mice. In this paper we will review the currently available literature on sST2 as a biomarker for adverse cardiovascular events. In addition, we will elaborate on the potential mechanistic role of the IL-33/ST2 pathway in chronic inflammatory cardiovascular diseases.
目前正在寻找能够促进亚临床或临床显性心血管疾病诊断的生物标志物。目前正在研究的一个新兴生物标志物是 ST2,它是白细胞介素-33(IL-33)的受体。ST2 是白细胞介素-1 受体家族的成员,由于选择性剪接,存在于跨膜(ST2L)和可溶性形式(sST2)中。一些研究小组报告了心血管疾病患者血清中 sST2 的升高。有越来越多的证据表明,sST2 可独立预测心力衰竭或心肌梗死患者的死亡率。除了作为不良心血管事件的生物标志物的潜在作用外,ST2 还被认为在动脉粥样硬化和心力衰竭等慢性心血管疾病中起因果作用。研究表明,IL-33 通过 ST2 信号传导在心肌梗死、心脏移植和心肌肥厚和纤维化的小鼠模型中具有心脏保护作用。此外,用 IL-33 治疗可减少动脉粥样硬化小鼠斑块的形成。本文将综述目前关于 sST2 作为不良心血管事件生物标志物的文献。此外,我们将详细阐述 IL-33/ST2 通路在慢性炎症性心血管疾病中的潜在机制作用。