Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, PR China.
Biochem Biophys Res Commun. 2010 Apr 9;394(3):836-42. doi: 10.1016/j.bbrc.2010.03.090. Epub 2010 Mar 17.
Oxidized low-density lipoprotein (ox-LDL) is an instrumental factor in atherogenesis, however, the effects of ox-LDL on the balance of Th17/Treg in acute coronary syndrome [ACS, including unstable angina (UA) and acute myocardial infarction (AMI)] is still unclear. CD4(+)CD25(+) regulatory T (Treg) cells and Th17 cells, subsets of T-helper cells, play important roles in peripheral immunity and their imbalance leads to the development of tissue inflammation and autoimmune diseases. However, few studies have explored the effect of Th17/Treg balance in plaque destabilization and the onset of ACS. To explore the shift of Th17/Treg balance in ACS patients and the effect of ox-LDL on the balance, we examined the frequencies of Th17 and Treg cells, key transcription factors and relevant cytokines in patients with AMI, UA, stable angina (SA) and controls. We analysed the correlations of serum ox-LDL to Th17/Treg frequency, and the effects of ox-LDL on Th17/Treg cells in vitro. Our study demonstrated that ACS patients have shown a significant increase of Th17 frequency, RORgammat expression and serum Interleukin 17 (IL-17), and a obvious decline of Treg frequency, Foxp3 expression, suppressive function, and serum IL-10. Serum ox-LDL positively correlated with the frequency of Th17 cells and negatively correlated with the frequency of Treg cells. In vitro incubation of peripheral blood mononuclear cells from controls with ox-LDL resulted in a significant reduction of Treg cells and a significant elevation of Th17 cells in a dose- and time-dependant manner. Treg and Th17 cells from ACS patients were significantly more susceptible to ox-LDL-mediated alterations. Th17/Treg numerical and functional imbalance exists in ACS patients, and ox-LDL has a direct effect on Th17/Treg imbalance which may contribute to the occurrence of ACS.
氧化型低密度脂蛋白(ox-LDL)是动脉粥样硬化形成的重要因素,然而,ox-LDL 对急性冠脉综合征(ACS,包括不稳定型心绞痛(UA)和急性心肌梗死(AMI))中 Th17/Treg 平衡的影响尚不清楚。CD4+CD25+调节性 T(Treg)细胞和 Th17 细胞是辅助性 T 细胞的两个亚群,在周围免疫中发挥重要作用,其失衡可导致组织炎症和自身免疫性疾病的发生。然而,很少有研究探讨 Th17/Treg 平衡在斑块不稳定性和 ACS 发病中的作用。为了探讨 ACS 患者 Th17/Treg 平衡的变化以及 ox-LDL 的作用,我们检测了 AMI、UA、稳定性心绞痛(SA)和对照组患者 Th17 和 Treg 细胞、关键转录因子和相关细胞因子的频率。我们分析了血清 ox-LDL 与 Th17/Treg 频率的相关性,以及 ox-LDL 对体外 Th17/Treg 细胞的作用。我们的研究表明,ACS 患者 Th17 频率、RORgammat 表达和血清白细胞介素 17(IL-17)明显升高,Treg 频率、Foxp3 表达、抑制功能和血清白细胞介素 10(IL-10)明显降低。血清 ox-LDL 与 Th17 细胞频率呈正相关,与 Treg 细胞频率呈负相关。体外孵育对照组外周血单个核细胞 ox-LDL 可导致 Treg 细胞显著减少,Th17 细胞显著增加,且呈剂量和时间依赖性。ACS 患者的 Treg 和 Th17 细胞对 ox-LDL 介导的改变更为敏感。ACS 患者存在 Th17/Treg 数量和功能失衡,ox-LDL 对 Th17/Treg 失衡有直接作用,可能导致 ACS 的发生。