Relationship of circulating caspases-1 and -8, their ratio with coronary artery atherosclerosis

Atherosclerosis is one of the leading causes of coronary heart disease. One of its pathogenetic mechanisms is chronic inflammation, in which the key role is played by enzymes of the protease family — caspases. Caspase-1 and caspase-8 are involved in the regulation of apoptosis and inflammatory responses; however, their circulating levels in atherosclerosis have not been studied. Objective. To analyze the relationship between the serum levels of caspase-1, caspase-8, and their ratio and the presence of atherosclerotic lesions of the coronary arteries. Materials and methods. The study included 144 patients aged 42 to 82 years with atherosclerotic lesions of the coronary arteries (CA) (n=91) and an intact CA comparison group (n=53). Caspase-1 and -8 serum levels were measured by enzyme immunoassay using reagents by R&D Systems (Bio-Techne Corporation R&D Systems, USA) and Ray-Biotech (RayBiotech Inc., USA). Results. The levels of caspase-1 were lower in patients in the group with CA lesions than in those with intact CAs (comparison group) (p=0.049), and the levels of caspase-8 were higher than in the comparison group (p=0.036). The median caspase-8/caspase-1 ratio in patients in the CA lesion group was 2 times higher than in the comparison group (p=0.0027). According to the ROC analysis, the caspase-8/caspase-1 ratio showed the largest area under the curve (AUC) of 0.649 (95% CI 0.560—0.738), and a ratio >1.9 was associated with CA atherosclerosis (diagnostic sensitivity 53.8%, diagnostic specificity 71.7%). Conclusion. The results indicate an imbalance in the secretion of caspase-8 and caspase-1 in the pathogenesis of coronary artery atherosclerosis and the potential to use the caspase-8/caspase-1 ratio as a marker of coronary artery damage.