The role of oxidized low-density lipoprotein in breaking peripheral Th17/Treg balance in patients with acute coronary syndrome
Introduction
Atherosclerosis (AS) is a chronic inflammatory disease in which immune mechanisms appear to make great effect, and atherogenesis involves various immune cells, particularly T lymphocytes, such as CD4+ T-helper cells [1], [2]. Acute coronary syndrome (ACS) occurs as a consequence of coronary plaque erosion or rupture and T lymphocytes play an important role in these coronary events [3]. CD4+CD25+ regulatory T (Treg) cells and T-helper 17 (Th17) cells are 2 original subsets distinguished from Th1 and Th2 cells. Treg cells expressing the forkhead/winged helix transcription factor (Foxp3), a fraction of inflammatory-regulated negative cells, have important effects on the maintenance of immune tolerance and immune homeostasis by contact-dependent suppression or by the release of anti-inflammatory cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-β[4]. Th17 cells expressing retinoic acid-related orphan receptor γt (RORγt) exert an important effect on the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions by producing IL-17, tumor necrosis factor (TNF)-α and IL-6 [5]. The Th17/Treg imbalance could be critical in the development of tissue inflammation and autoimmune diseases [6]. However, Th17/Treg balance in AS, especially ACS patients has not been fully investigated.
Oxidized low-density lipoprotein (ox-LDL) is a key factor in the initiation and progression of atherosclerosis and contributes to endothelial dysfunction and plaque destabilization through multiple mechanisms [7], [8]. It is unclear whether ox-LDL also affects AS and ACS patients by disrupting the balance of the peripheral Tregs and Th17 cells.
In this study, we have examined the balance of Th17/Treg cells in ACS patients, and the effects of ox-LDL on these cells.
Section snippets
Patients
All patients gave written informed consent prior enrolment into the study. We examined patients at Anhui provincial hospital who underwent diagnostic catheterisation between July 2007 and June 2009. Patients were classified into 4 groups: acute myocardial infarction (AMI) patients, unstable angina (UA) patients, stable angina (SA) patients and control subjects with normal coronary arteries (NCA), Patients with ACS and SA had a similar extent of coronary atherosclerosis. There were no evident
Characteristics of patients
Table 1 shows the characteristics of patients. There were no significant differences in age, gender, CAD extent, hypertension, diabetes mellitus, smoking rate, obesity, high-density lipoprotein-cholesterol (HDL-C), and very low-density lipoprotein-cholesterol (VLDL-C) concentrations among patients with AMI, UA, and SA.
Decrease of Treg cells in ACS patients
The frequencies of Treg (CD4+CD25high/CD4+, CD4+CD25+CD127lo/CD4+, and CD4+CD25+Foxp3+/CD4+ T cells) cells were significantly lower in AMI and UA patients than in the SA and NCA
Discussion
Our study indicate that the shift of the Th17/Treg cell balance from Treg cells towards Th17 cells exists in ACS patients, and that this ox-LDL-mediated change is associated with the imbalance of Th17/Treg cells.
Treg cells may suppress proatherogenic immune responses partly by secretion of anti-inflammatory cytokines, such as IL-10. The normal function of Treg cells may be essential to maintain the homeostasis of different subsets of T cells in the vessel wall [12]. There are reduced numbers of
Acknowledgments
This work was supported by National Natural Science Foundation of China (No. 30971226) and Natural Science Foundation of Anhui province of China (No. 090413091).
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These authors contributed equally to this work.