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The role of oxidized low-density lipoprotein in breaking peripheral Th17/Treg balance in patients with acute coronary syndrome

Update time: 7/8/2010 2:37:26 AM  Views: 22  【 Font: Large Medium Small 】【Print

 

Qing Lia, b, c, d, 1, Yi Wanga, b, c, 1, Ke Chene, Qing Zhoua, b, c, Wei Weia, c, Yiping Wangf and Yuan Wanga, b, c, Corresponding Author Contact Information, E-mail The Corresponding Author

a Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, PR China

b Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, Anhui 230032, PR China

c Key Laboratory of Gene Resource Utilization for Severe Disease and Anti-inflammatory and Immunopharmacology (Anhui Medical University), Ministry of Education and Anhui Province, Hefei, Anhui 230032, PR China

d The Central Laboratory of Medical Research Center, Anhui Provincial Hospital, Hefei, Anhui 230001, PR China

e Department of Cardiovascular Disease, Anhui Provincial Hospital, Hefei, Anhui 230001, PR China

f The Centre for Transplantation and Renal Research, Western Clinical School, University of Sydney, Westmead, NSW Australia

Received 6 March 2010. 
Available online 17 March 2010.

Abstract

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, RORγt 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.

Keywords: Oxidized low-density lipoprotein; Acute coronary syndrome; T-helper 17; Regulatory T cells

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