Crosstalk Between Enzyme Matrix Metalloproteinases 2 and 9 and Regulatory T Cell Immunity in the Global Burden of Atherosclerosis

Scand J Immunol. 2017 Jul;86(1):65-71. doi: 10.1111/sji.12563.

Abstract

Changes in immune and inflammatory responses may play a crucial role in the development and progression of atherosclerosis, as an autoimmune, chronic and progressive inflammatory disease. Immunological activity and vascular inflammation during atherosclerosis can be modulated by autoimmune responses against self-antigens, according to changeable risk factors (cholesterol, oxidized low-density lipoprotein (ox-LDL) in the vascular wall, fatty acids, etc.), and accompanied by accumulation of leucocytes and proinflammatory cytokines, which stimulate the transcription of matrix metalloproteinases (MMPs), whose concentration are increased in foam cell-rich regions. Regulatory T cells (Tregs) represent a unique subpopulation of T cells specialized in the regulation of immune response and in the suppression of proatherogenic T cells. The aim of our study was to examine the interactions between the concentration of enzyme matrix metalloproteinases 2 and 9 (MMP-2 and 9) in urine and the percentage of Tregs in peripheral blood of two groups of patients: with carotid artery stenosis (CAS), undergoing surgery and with mild atherosclerosis (A) from general practice. The method of enzyme immunoassay (ELISA) was used to determine enzyme MMP expression, and Tregs was examined by flow cytometric analysis. Our data have showed a large increase in the enzyme MMP-2 and 9 in the urine of CAS and A patients in comparison with healthy controls and indicated this method as an easy marker for the monitoring of the development of atherosclerosis. Simultaneously, the diminished number of Tregs in the same patients pointed the importance of these regulatory mechanisms in the etiopathogenesis of atherosclerosis and possible Tregs-mediated therapy.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atherosclerosis / blood
  • Atherosclerosis / immunology*
  • Atherosclerosis / urine
  • Carotid Stenosis / blood
  • Carotid Stenosis / immunology
  • Carotid Stenosis / urine
  • Cholesterol / immunology
  • Cholesterol / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Global Burden of Disease / statistics & numerical data
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Lipoproteins, LDL / immunology
  • Lipoproteins, LDL / metabolism
  • Male
  • Matrix Metalloproteinase 2 / immunology*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 2 / urine
  • Matrix Metalloproteinase 9 / immunology*
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase 9 / urine
  • Middle Aged
  • Protein Binding
  • Risk Factors
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Cholesterol
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9