Advances in Clinical and Experimental Medicine
2019, vol. 28, nr 9, September, p. 1243–1248
Publication type: original article
The influence of statin monotherapy and statin-ezetimibe combined therapy on FoxP3 and IL 10 mRNA expression in patients with coronary artery disease
1 Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Poland
Background. FoxP3 is a marker of human T regulatory cells (Tregs), which are supposed to play an important role in the pathophysiology of atherosclerosis. Interleukin 10 (IL-10) is a cytokine with pleiotropic, immunoregulatory properties, produced mostly by Tregs and B regulatory cells. Due to their anti-inflammatory action, both Tregs and IL-10 are believed to inhibit plaque development and decrease atherosclerosis progression. The effect of hypolipidemic drugs – statins or ezetimibe – on FoxP3-positive Tregs and anti-inflammatory cytokines, such as IL-10, is still unclear.
Objectives. The objective of the study was to investigate the effects of 3 different therapies of equivalent hypolipidemic activity: atorvastatin, rosuvastatin, and combination therapy of atorvastatin and ezetimibe on FoxP3–Tregs transcription factor and IL-10 mRNA expression in peripheral blood mononuclear cells (PBMCs) from patients with stable coronary artery disease (CAD).
Material and Methods. Sixty-five patients with diagnosed CAD participated in the study. They were randomly assigned to 3 therapeutic groups: atorvastatin at a dose of 40 mg/day (A40 group); rosuvastatin 20 mg/day (R20 group); and atorvastatin 10 mg/day combined with ezetimibe 10 mg/day (A10+E10 group). After 1 month and 6 months of therapy, the mRNA expression for FoxP3 and IL-10 in PBMCs was evaluated using real-time polymerase chain reaction (RT-PCR) and lipid parameters.
Results. An improvement in lipid parameters was observed in each of the groups studied; however, hypolipidemic treatment did not induce any change in FoxP3 and IL-10 mRNA expression. After 6 months, an increase in FoxP3 mRNA expression was noted in A40 group as compared to R20 group.
Conclusion. None of the therapies of equal hypolipidemic efficacy affected FoxP3 and IL-10 mRNA expression in patients with stable CAD.
statins, ezetimibe, FOXP3, IL-10, regulatory T cells
- Davidson MH, Palmisano J, Wilson H, Liss C, Dicklin MR. A multicenter, randomized, double-blind clinical trial comparing the low-density lipoprotein cholesterol-lowering ability of lovastatin 10, 20, and 40 mg/d with fluvastatin 20 and 40 mg/d. Clin Ther. 2003;25(11):2738–2753.
- Reiner Z, Catapano AL, De Backer G, et al; European Association for Cardiovascular Prevention & Rehabilitation; ESC Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32(14):1769–1818.
- Foks AC, Lichtman AH, Kuiper J. Treating atherosclerosis with regulatory T cells. Arterioscler Thromb Vasc Biol. 2015;35(2):280–287.
- Ng TH, Britton GJ, Hill EV, Verhagen J, Burton BR, Wraith DC. Regulation of adaptive immunity: The role of interleukin-10. Front Immunol. 2013;4:129.
- Akdis CA, Akdis M. Mechanisms of immune tolerance to allergens: Role of IL-10 and Tregs. J Clin Invest. 2014;124(11):4678–4680.
- Pinderski Oslund LJ, Hedrick CC, Olvera T, et al. Interleukin-10 blocks atherosclerotic events in vitro and in vivo. Arterioscler Thromb Vasc Biol. 1999;19(12):2847–2853.
- Meng X, Zhang K, Li J, et al. Statins induce the accumulation of regulatory T cells in atherosclerotic plaque. Mol Med. 2012;18:598–605.
- Mausner-Fainberg K, Luboshits G, Mor A, et al. The effect of HMG-CoA reductase inhibitors on naturally occurring CD4+CD25+ T cells. Atherosclerosis. 2008;197(2):829–839.
- Rodriguez-Perea AL, Montoya CJ, Olek S, Chougnet CA, Velilla PA. Statins increase the frequency of circulating CD4+ FOXP3+ regulatory T cells in healthy individuals. J Immunol Res. 2015;2015:762506.
- Wang ZX, Wang CQ, Li XY, Ding Y, Feng GK, Jiang XJ. Changes of naturally occurring CD4(+)CD25(+) FOXP3(+) regulatory T cells in patients with acute coronary syndrome and the beneficial effects of atorvastatin treatment. Int Heart J. 2015;56(2):163–169.
- Hu Z, Li D, Hu Y, Yang K. Changes of CD4+CD25+ regulatory T cells in patients with acute coronary syndrome and the effects of atorvastatin. J Huazhong Univ Sci Technolog Med Sci. 2007;27(5):524–527.
- Zhang D, Wang S, Guan Y, et al. Effect of oral atorvastatin on CD4+CD25+ regulatory T cells, FoxP3 expression, and prognosis in patients with ST-segment elevated myocardial infarction before primary percutaneous coronary intervention. J Cardiovasc Pharmacol. 2011;57(5):536–541.