Regulatory T cells suppress the expression of COX-2 in vulnerable plaque

Heart Vessels. 2020 Feb;35(2):278-283. doi: 10.1007/s00380-019-01491-1. Epub 2019 Sep 9.

Abstract

COX-2 contributes to local inflammation in atherosclerotic lesions. Regulatory T cells (Tregs) enhance the stability of atherosclerotic plaques. The aim of this study was to detect the potential relationship between Tregs and COX-2 in vulnerable plaques. Thirty ApoE -/- mice were fed a high-fat diet, and a silastic perivascular collar was placed around the right common carotid artery to induce vulnerable plaques. Eight weeks after collar placement, the mice were divided randomly into three groups: control, PBS, and Treg groups. Four weeks later, the right common carotid arteries were collected to detect the expression of COX-2. The results showed that Tregs significantly suppressed the expression of COX-2 in vulnerable plaques. In an in vitro experiment, RAW264.7 cells were divided randomly into three groups, which were precultured without T cells or with CD4 + CD25- T cells or Tregs for 48 h with an anti-CD3 antibody; then the cells were stimulated with LPS for 24 h. The RAW264.7 cells were harvested for RT-PCR and western blot assays and the results showed that Tregs downregulated COX-2 expression in RAW264.7 cells. Therefore, Tregs inhibited the expression of COX-2 in vulnerable plaques and macrophages, and COX-2 inhibition may be an important effect of Tregs that results in atherosclerotic plaque stabilization.

Keywords: Atherosclerosis; Cyclooxygenase-2; Plaque instability; Regulatory T cells.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Carotid Artery Diseases / enzymology*
  • Carotid Artery Diseases / immunology
  • Carotid Artery Diseases / pathology
  • Carotid Artery Diseases / prevention & control
  • Carotid Artery, Common / enzymology*
  • Carotid Artery, Common / immunology
  • Carotid Artery, Common / pathology
  • Cell Communication*
  • Coculture Techniques
  • Cyclooxygenase 2 / metabolism*
  • Disease Models, Animal
  • Down-Regulation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Plaque, Atherosclerotic*
  • RAW 264.7 Cells
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / transplantation

Substances

  • Ptgs2 protein, mouse
  • Cyclooxygenase 2