Department of Immunology, Shandong University School of Medicine, Jinan, China.
Clin Immunol. 2011 Nov;141(2):152-60. doi: 10.1016/j.clim.2011.07.003. Epub 2011 Aug 3.
Th17 cells producing IL-17 are involved in the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. In this study, we investigated the effects of IL-17 on human vascular endothelial cells and showed that IL-17 induced cell death of the vascular endothelial cells, which played a pivotal role in plaque destabilization triggering acute coronary syndrome (ACS). We showed that circulating Th17 cells and IL-17 increased in patients with ACS compared to the patients with stable angina or health individuals; the plasma levels of IL-6 increased but TGF-β decreased in ACS patients, exhibiting a positive and negative correlation with that of IL-17, respectively. Importantly, we uncovered that IL-17 promoted the production of von Willebrand factor by endothelial cells and induced endothelial apoptosis by activating caspase-3, caspase-9 and up-regulating the ratio of Bax/Bcl-2, indicating the function of IL-17 in vascular endothelial damage as a potential mechanism for the pathogenesis of human ACS.
Th17 细胞产生的白介素-17 参与动脉粥样硬化的发病机制，但潜在机制尚不清楚。在这项研究中，我们研究了白介素-17 对人血管内皮细胞的影响，结果表明白介素-17 诱导血管内皮细胞死亡，这在斑块不稳定引发急性冠状动脉综合征（ACS）中起着关键作用。我们发现，与稳定型心绞痛患者或健康个体相比，ACS 患者的循环 Th17 细胞和白介素-17 增加；ACS 患者的血浆白介素-6 水平升高，但 TGF-β 水平降低，与白介素-17 呈正相关和负相关。重要的是，我们发现白介素-17 通过激活半胱氨酸蛋白酶-3、半胱氨酸蛋白酶-9 并上调 Bax/Bcl-2 比值，促进内皮细胞中血管性血友病因子的产生，并诱导内皮细胞凋亡，表明白介素-17 在血管内皮损伤中的功能是人类 ACS 发病机制的潜在机制。
