Circulating Exosomal CircRNAs as Diagnostic Biomarkers for Chronic Coronary Syndrome

Circular RNA (circRNA) has been reported to be involved in the pathogenesis of cardiovascular disease; however, it is unclear whether circRNA carried by exosomes (exos) can be used as biomarkers for chronic coronary syndrome (CCS). High-throughput sequencing was carried out in the plasma exosomal RNA of 15 CCS patients and 15 non-cardiac chest pain patients (NCCP, control group) to screen for differentially expressed circRNAs. Selected differentially expressed exo-circRNAs were further verified by real-time polymerase chain reaction in a small-sample cohort and a large-sample cohort. A total of 276 circRNAs were differentially expressed in the plasma exosomes of CCS patients, with 103 up-regulated and 173 down-regulated. Among the 103 up-regulated circRNAs, 5 circRNAs with high expression levels were selected for validation. Real time quantitative PCR of the first and second validation cohort demonstrated that exo-hsa_circ_0075269 and exo-hsa_circ_0000284 were significantly up-regulated in patients with CCS. Circulating exo-hsa_circ_0075269 and exo-hsa_circ_0000284 yielded the area under the curve values of 0.761 (p < 0.001, 95%CI = 0.669, 0.852) and 0.623 (p = 0.015, 95%CI = 0.522, 0.724) for CCS, respectively, by ROC curve analysis. In conclusion, the expression profile of circRNA in plasma exosomes of patients with CCS was significantly different from that of the control group. Plasma exo-hsa_circ_0075269 and exo-hsa_circ_0000284 have the potential to be new biomarkers for CCS.