The influence of statin monotherapy and statin-ezetimibe combined therapy on FoxP3 and IL 10 mRNA expression in patients with coronary artery disease

Adv Clin Exp Med. 2019 Sep;28(9):1243-1248. doi: 10.17219/acem/108627.

Abstract

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.

Conclusions: None of the therapies of equal hypolipidemic efficacy affected FoxP3 and IL-10 mRNA expression in patients with stable CAD.

Keywords: FOXP3; IL-10; ezetimibe; regulatory T cells; statins.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Anticholesteremic Agents* / therapeutic use
  • Atorvastatin / therapeutic use
  • Coronary Artery Disease* / genetics
  • Coronary Artery Disease* / metabolism
  • Ezetimibe / therapeutic use
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Interleukin-10 / metabolism
  • Leukocytes, Mononuclear
  • RNA, Messenger

Substances

  • Anticholesteremic Agents
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • RNA, Messenger
  • Interleukin-10
  • Atorvastatin
  • Ezetimibe