Circulating markers of autophagy dysfunction are associated with coronary artery disease in patients undergoing coronary angiography

Abstract Background Despite advances in prevention, diagnosis, and treatment, coronary artery disease (CAD) remains the predominant cause of cardiovascular-related deaths. Autophagy is a conserved intracellular degradation process essential for cellular homeostasis. It clears damaged organelles and misfolded proteins via autophagy-related (ATG) proteins. Studies in animal models indicated that dysregulated autophagy contributes to atherosclerosis development by promoting oxidative stress, inflammation, and endothelial dysfunction. However, the complex interplay between autophagy dysfunction and atherosclerotic artery disease in patients remains poorly understood. Purpose This study aimed at evaluating the association between autophagy dysfunction markers and the presence and severity of CAD in patients. Methods This prospective observational study included 128 consecutive patients (aged 18–85 years, LVEF 50%) undergoing coronary angiography (CAG) for suspected CAD. Patients were stratified into three groups: 33 with acute coronary syndrome (ACS), 64 with chronic coronary syndrome (CCS), and 31 without significant coronary disease. Serum levels of autophagy markers P62 and ATG5 were measured within 48 hours post-CAG using ELISA. A reduction in ATG5 and an increase in P62 are recognized markers of impaired autophagy, with P62/ATG5 ratio serving as an indicator of autophagic dysfunction. Clinical, biochemical, radiological, and echocardiographic parameters were assessed. Results Both decreased ATG5 (p=0.025) and increased P62 (p=0.04) levels were correlated with multivessel CAD. The t-test confirmed a significantly higher P62/ATG5 ratio in CAD (p=0.05). Patients with multi-vessel CAD exhibited higher P62/ATG5 levels than those with single-vessel disease (p=0.002, Kruskal-Wallis test). Mann-Whitney analysis showed the most significant differences between single-vessel and multi-vessel CAD (p0.001) and between multi-vessel CAD and disease-free patients (p=0.006). No significant difference was found between ACS and CCS groups. P62/ATG5 ratio was also significantly higher in patients with carotid artery disease (P0.05). Conclusion An increased P62/ATG5 ratio, reflecting autophagy dysfunction, is significantly associated with CAD and carotid artery disease. These findings suggest that autophagy markers could serve as novel prognostic and diagnostic tools in atherosclerotic disease. Further research is warranted to explore autophagy as a potential therapeutic target in cardiovascular pathology.