The Interplay of Inflammatory Cytokines, Epigenetic Biomarkers and Cardiac Imaging Features in Coronary Artery Disease Progression: A Multimarker Approach

Abstract

This study evaluated the significance of a multibiomarker model, including an epigenetic marker (miR-155), inflammatory cytokines (TNF-α, IL-1β) and noninvasive cardiac imagining patterns, for assessing the risk of progressive coronary artery disease (CAD). A comprehensive assessment of correlations between the parameters of coronary atherosclerosis according to contrast MSCT angiography (coronary calcium score, degree of stenosis, remodeling index, segment involvement score -SIS, density, volume and mass of plaques) and biomarker levels was carried out in 152 patients with stable and unstable forms of coronary artery disease. miR-155 expression was determined using a Rotor-Gene Q device by real-time polymerase chain reaction (qRT-PCR), and concentrations of proinflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). We hypothesized that the combined assessment of these biomarkers would improve risk stratification compared to the analysis of individual biomarkers. There were fairly close positive correlations of miR-155 with IL-1 (r=0.54; p<0.01) and TNF-α (r=0.57; p<0.01). It is noteworthy that the nature and strength of these associations varied depending on the clinical form of CAD. The study revealed significant correlations between the levels of inflammatory markers (TNF-α, IL-1β, IL-4), miR-155, and MSCT angiography in patients with various forms of CAD. In patients with unstable angina (UA), TNF-α, IL-1β, and miR-155 levels showed strong positive correlations with signs of the prevalence and vulnerability of atherosclerosis: SIS index, degree of stenosis, remodeling index (RI), plaque volume and mass (r up to 0.88; p<0.001), and They are also negative with plaque density (r =-0.80; p<0.001). On the contrary, IL-4 had reverse bonds, especially pronounced in HC (RI: r=-0.70; plaque volume: r=-0.71), confirming its protective role. The inflammatory response index (IRI = (IL-1β + TNF-α)/IL-4) showed high prognostic value in HC, correlating with the main signs of plaque instability. The expression of miR-155 was also closely associated with active forms of atherosclerosis. In the stable angina group, similar associations persisted, but were less pronounced. The data obtained emphasize the importance of assessing the inflammatory profile and miR-155 in combination with MSCT data for risk stratification and detection of signs of atherosclerotic plaque instability in patients with CAD. These results highlight the key role of inflammatory and epigenetic mechanisms in the destabilization of atherosclerotic plaques and their morphological expression. The data obtained indicate that this multibiomarker panel can become a valuable tool for early detection, risk assessment, and the development of individual management strategies for patients with CAD.