Advancing coronary artery disease diagnosis: Profiling of long noncoding RNAs in small extracellular vesicles from peripheral blood mononuclear cells

Long noncoding RNAs (lncRNAs) play pivotal roles in various physiological processes and significantly influence the pathogenesis of cardiovascular diseases. This study aims to explore the potential clinical utility of lncRNAs as serological biomarkers for diagnosing coronary artery disease (CAD). To investigate lncRNA expression profiles, we utilized a lncRNA microarray to analyze small extracellular vesicles (sEVs) isolated from peripheral blood monocytes of 3 CAD patients and 3 age- and sex-matched healthy controls. Differentially expressed lncRNAs in both plasma and monocyte-derived sEVs were validated using quantitative real-time polymerase chain reaction. A diagnostic model for CAD, integrating lncRNA expression data, was developed through Random Forest and nomogram analyses. The analysis identified 89 lncRNAs that were upregulated and 211 that were downregulated in CAD patients compared to healthy controls. Notably, SNAR-E was significantly upregulated, while RPL34-AS1 showed marked downregulation. SNAR-E expression was positively correlated with diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Conversely, RPL34-AS1 expression correlated with age, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, and lipoprotein (a). Both SNAR-E and RPL34-AS1 exhibited high diagnostic accuracy for CAD in plasma and sEVs, demonstrating elevated sensitivity and specificity. The diagnostic model demonstrated robust predictive performance and reliability. SNAR-E and RPL34-AS1, detected in sEVs and plasma, offer superior sensitivity and specificity for CAD diagnosis compared to conventional noninvasive diagnostic methods. The diagnostic model integrating these 2 lncRNAs demonstrates substantial accuracy and stability, potentially facilitating early CAD detection and informing clinical decision-making.