LPS differentially affects expression of CD14 and CCR2 in monocyte subsets of Post-STEMI patients with hyperglycemia

Diabetes Res Clin Pract. 2022 Sep:191:110077. doi: 10.1016/j.diabres.2022.110077. Epub 2022 Sep 8.

Abstract

Aims: Following ST-segment elevation myocardial infarction (STEMI), recruitment and activation of monocytes [classical (CD14++CD16-CCR2++), intermediate (CD14++CD16+CCR2+), non-classical (CD14LowCD16++CCR2Low)] are needed for myocardial wound healing. Monocyte surface receptor CC chemokine receptor type 2 (CCR2) is responsible for monocyte chemotaxis to sites of inflammation and the lipopolysaccharide (LPS)-binding protein co-receptor, CD14, is involved in pro-inflammatory monocyte activation. The purpose of this investigation was to determine the effects of ex-vivo LPS activation on monocyte subset CD14 and CCR2 expression in post-STEMI individuals with normal and elevated random blood glucose.

Methods: Post-STEMI subjects were identified as normal random glucose (NG, <98 mg/dL, n = 13) or impaired random glucose (IG, ≥98 mg/dL, n = 26) and monocytes were analyzed for non-activated and LPS-activated (1 µg/mL for 4 h) CCR2 and CD14 expression.

Results: Non-activated intermediate monocytes from IG showed decreased CD14 expression when compared to NG, which was maintained following LPS-activation. The NG group showed a larger absolute reduction in classical CCR2 expression, leading to a significant difference between NG and IG following LPS-activation.

Conclusion: Results suggest a heightened response to pro-inflammatory activation in IG following STEMI, which may impair or delay post-STEMI myocardial healing, and thus increase the incidence of chronic heart failure. NIH 1R34HL121402.

Keywords: CCR2; CD14; CHF; Glucose; Inflammation; LPS; Monocyte; STEMI.

MeSH terms

  • Blood Glucose / metabolism
  • Humans
  • Hyperglycemia* / metabolism
  • Lipopolysaccharide Receptors / immunology*
  • Lipopolysaccharides / pharmacology
  • Monocytes / metabolism
  • Receptors, CCR / metabolism
  • Receptors, CCR2 / metabolism
  • Receptors, IgG / metabolism
  • ST Elevation Myocardial Infarction*

Substances

  • Blood Glucose
  • CCR2 protein, human
  • CD14 protein, human
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Receptors, CCR
  • Receptors, CCR2
  • Receptors, IgG