JAK3 in coronary heart disease: diagnostic and prognostic value

The JAK/STAT signaling pathway plays a key role in regulation of inflammatory and reparative processes in cardiovascular diseases. Interest in JAK3, which is predominantly expressed in immune cells, cardiomyocytes, and vascular endothelium, has increased significantly over recent decades while suggesting a complex immunopathological process underlying acute coronary events in coronary artery disease. However, its role as a circulating biomarker remains poorly understood. Our objective was to evaluate serum JAK3 levels in patients with acute myocardial infarction and stable coronary artery disease. A total of 70 persons were included in the single-center cross-sectional observational study: 25 patients with acute myocardial infarction (with angiographically confirmed coronary artery occlusion), 25 with stable ischemic heart disease, and 20 healthy individuals matched for gender and age. Blood was collected during the first 24 hours of hospitalization at the Orel Regional Clinical Hospital. The JAK3 level was determined in serum using enzyme-linked immunosorbent assay. The JAK3 level in the serum of patients with stable ischemic heart disease was significantly lower compared to the control group of healthy individuals (p = 0.012). The most pronounced decrease was recorded in the group of patients with acute myocardial infarction, with a median concentration of 358.00 pg/ml, which is 3.3 times lower than in healthy individuals (p 0.001). The lowest values of JAK3 were recorded in total occlusion of the coronary arteries according to coronary angiography. Negative correlations were established between the JAK3 level and laboratory markers of inflammation and cytolysis: leukocytes (ρ = -0.585), platelets (ρ = -0.759), ESR (ρ = -0.674), ALT (ρ = -0.761) and AST (ρ = -0.730) (p 0.05 in all series). Positive correlations with STAT1, STAT3 and STAT6 were also revealed. The decrease in JAK3 levels in a coronary event likely reflects depletion of the intracellular pool of Janus kinase due to hyperactivation of the signaling pathway. Serum JAK3 levels could potentially be considered a new integrative biomarker not only for assessing JAK/STAT signaling activity but also for risk stratification and assessing the severity of coronary artery disease.