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Features of the monocyte inflammatory response in patients with premature coronary artery disease

Tatiana Blokhina1, Tatiana Kirichenko2,3, Yuliya Markina3

  • 1Department of problems of atherosclerosis, Chazov National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, 121552 Moscow, Russia.

Biophysics Reports
|March 12, 2025
PubMed

Insights

Patients with premature coronary artery disease (CAD) exhibit higher basal secretion of inflammatory cytokines from monocytes/macrophages. These elevated cytokine levels, including IL-1β and IL-6, are independently associated with premature CAD risk factors.

Area of Science:

  • Immunology
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Premature coronary artery disease (CAD) poses a significant health burden.
  • Inflammatory processes, particularly involving monocytes/macrophages, are implicated in CAD pathogenesis.
  • Understanding cytokine secretion patterns in premature CAD is crucial for identifying novel therapeutic targets.

Purpose of the Study:

  • To investigate the inflammatory cytokine secretion profiles of cultured monocytes/macrophages from patients with premature CAD.
  • To compare basal and lipopolysaccharide (LPS)-stimulated cytokine secretion between premature CAD patients and controls.
  • To identify specific cytokines and clinical factors associated with premature CAD.

Main Methods:

  • Primary culture of CD14+ monocytes isolated from 38 premature CAD patients and 35 controls using immunomagnetic separation.
  • Induction of inflammatory response via LPS stimulation on Days 1 and 6.
  • Quantification of basal and stimulated tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) secretion using enzyme immunoassay on Days 2 and 7.

Main Results:

  • Patients with premature CAD showed significantly higher basal secretion of TNF-α, IL-1β, IL-6, and MCP-1 compared to controls.
  • Re-stimulated TNF-α and LPS-stimulated/re-stimulated IL-1β secretion were elevated in the CAD group.
  • While LPS-stimulated MCP-1 did not differ, re-stimulated MCP-1 secretion was higher in CAD patients.
  • Logistic regression identified basal IL-1β and IL-6 secretion, smoking, BMI, and HDL-cholesterol as independent predictors of premature CAD.

Conclusions:

  • Monocytes/macrophages from patients with premature CAD exhibit an enhanced inflammatory secretory phenotype.
  • Basal secretion levels of IL-1β and IL-6 are significant independent predictors of premature CAD.
  • These findings highlight the role of monocyte-derived inflammation in the development of premature CAD and suggest potential biomarkers.

Keywords:
Coronary artery diseaseImmune toleranceInflammatory cytokinesMonocytes

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