Study of the NLRP3 inflammasome component genes and downstream cytokines in patients with type 2 diabetes mellitus with carotid atherosclerosis

Lipids Health Dis. 2017 Nov 18;16(1):217. doi: 10.1186/s12944-017-0595-2.

Abstract

Background: A role for the NLRP3 inflammasome has been reported in various diseases, such as diabetes mellitus, atherosclerosis (AS), nephropathy, rheumatism, and others, although limited information is available concerning the role of the NLRP3 inflammasome, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in patients with type 2 diabetes mellitus (T2DM) and carotid atherosclerosis (CAS). Therefore, this cross-sectional study investigated these inflammatory components in patients with T2DM complicated with carotid atherosclerosis (T2DM + CAS).

Methods: A total of 107 inpatients or outpatients were included,including 81 T2DM + CAS patients and 26 T2DM patients. Patients with T2DM or T2DM + CAS were recruited to compare the expression levels of NLRP3 pathway genes (NLRP3, ASC and caspase-1 mRNA) and the serum IL-1β and IL-18 concentrations. In the T2DM + CAS group, patients with thickened intima media thickness (IMT) and those with plaques were compared, and the correlation of the 5 variables with Crouse scores were analyzed.

Results: The expression of NLRP3 pathway genes except caspase-1 was significantly higher in patients with T2DM and CAS compared to T2DM patients. Serum IL-1β and IL-18 concentrations shows no difference between the T2DM + CAS and T2DM group. In the T2DM + CAS group, the expression levels of the three inflammasome genes and IL-18 were increased in patients with thickened IMT compared to those with the plaque. All of the above factors negatively correlated with Crouse scores.

Conclusion: NLRP3 inflammasome pathway activity is significantly increased in patients with AS and T2DM at the early stage of plaque formation.

Keywords: Cytokines,type 2 diabetes mellitus,carotid atherosclerosis; NLRP3.

MeSH terms

  • Adult
  • Aged
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / metabolism
  • Carotid Artery Diseases / complications
  • Carotid Artery Diseases / genetics
  • Carotid Artery Diseases / metabolism*
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Cross-Sectional Studies
  • Cytokines / genetics*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Inflammasomes / genetics*
  • Inflammasomes / metabolism
  • Interleukin-18 / genetics
  • Interleukin-1beta / genetics
  • Male
  • Middle Aged
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism

Substances

  • CARD Signaling Adaptor Proteins
  • Cytokines
  • IL18 protein, human
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • PYCARD protein, human
  • Caspase 1