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. 2024 Sep 4;14(9):1119.
doi: 10.3390/biom14091119.

Vascular Cytokines and Atherosclerosis: Differential Serum Levels of TRAIL, IL-18, and OPG in Obstructive Coronary Artery Disease

Katharine A Bate  1   2 , Elijah Genetzakis  1 , Joshua Vescovi  1   3   4 , Michael P Gray  1 , David S Celermajer  5   6   7 , Helen M McGuire  5   8 , Stuart M Grieve  9   10 , Stephen T Vernon  1   2 , Siân P Cartland  6 , Jean Y Yang  3   4   11 , Mary M Kavurma  6 , Gemma A Figtree  1   2   5
Affiliations

Vascular Cytokines and Atherosclerosis: Differential Serum Levels of TRAIL, IL-18, and OPG in Obstructive Coronary Artery Disease

Katharine A Bate et al. Biomolecules. .

Abstract

The risk-factor-based prediction of atherosclerotic coronary artery disease (CAD) remains suboptimal, particularly in the absence of any of the standard modifiable cardiovascular risk factors (SMuRFs), making the discovery of biomarkers that correlate with atherosclerosis burden critically important. We hypothesized that cytokines and receptors associated with inflammation in CAD-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interleukin-18 (IL-18), and osteoprotegerin (OPG)-would be independently associated with CAD. To determine this, we measured the serum biomarker levels of 993 participants from the BioHEART study who had CT coronary angiograms that were scored for severity of stenosis and plaque composition. We found that the quartiles of TRAIL, OPG, and IL-18 were significantly associated with disease scores, and that the IL-18/TRAIL and OPG/TRAIL ratios demonstrated significant differences between no CAD vs. STEMI whereas only the OPG/TRAIL ratio showed differences between no CAD and obstructive CAD (stenosis > 50%). However, these associations did not persist after adjustment for age, sex, SMuRFs, and a family history of CAD. In conclusion, TRAIL, IL-18, and OPG and the derived ratios of IL-18/TRAIL and OPG/TRAIL demonstrate significant associations with raw disease scores and risk factors, but these markers are not discriminatory biomarkers for the prediction of CAD when incorporated into multi-variable risk models.

Keywords: atherosclerosis; biomarkers; coronary artery disease; cytokines; risk factors.

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Conflict of interest statement

GAF reports personal consulting fees from CSL and grants from Abbott Diagnostic unrelated to the submitted work. In addition, GAF has a patent Biomarkers and Oxidative Stress awarded USA May 2017 (US9638699B2) issued to Northern Sydney Local Health District, St Leonards, NSW, Australia. The other authors have no disclosures. The authors declare no conflicts of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Log-transformed levels of (A) TRAIL, (B) IL-18, (C) OPG, (D) IL-18/TRAIL ratio, and (E) OPG/TRAIL ratio in CTCA and STEMI patients. CAD: coronary artery disease; IL-18: interleukin-18; IQR: interquartile range; OPG: osteoprotegerin; STEMI: ST-elevation myocardial infarction; TRAIL: tumor necrosis factor-related apoptosis-inducing ligand. *** p < 0.001. Coefficients from linear regression models are presented in Supplementary Table S1.
Figure 2
Figure 2
Kendall’s tau correlation (τb) heatmap for biomarker quartiles and disease score (A), and Spearman’s correlation (ρ) heatmap for biomarker levels with age, BMI, and the number of SMuRFs (B). * p < 0.05.
Figure 3
Figure 3
Odds ratios for the incidence of CAD from univariate and multivariable logistic regression models for TRAIL, IL-18, OPG, and the IL-18/TRAIL or OPG/TRAIL ratios.
See this image and copyright information in PMC

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