Diagnostic potential of circular RNAs in carotid atherosclerotic plaque vulnerability

Vulnerable carotid atherosclerotic plaques are prone to cap rupture and thrombosis, yet definitive assessment still relies on postoperative histology. We investigated whether circulating circular RNAs (circRNAs) in peripheral blood mononuclear cells (PBMCs) can identify plaque vulnerability preoperatively.

In patients undergoing carotid endarterectomy, plaques were classified as vulnerable or stable, and PBMC expression of candidate circRNAs (circVIRMA, circGRN, circANRIL and CDR1as) and paired linear transcripts was quantified by RT-qPCR. A composite in-plaque_SCORE (IL-1β, IL-6, IL-10, PPARγ mRNAs) characterized intraplaque inflammation. We derived two PBMC metrics: circRNA_SCORE (mean expression of deregulated circRNAs) and circ/linear mRNA_SCORE (mean of circ/linear mRNA expression ratios) and evaluated diagnostic performance by Receiver Operating Characteristic curve (ROC) analysis and logistic regression.

circVIRMA and circGRN were modestly increased in PBMCs from patients with vulnerable plaques, whereas linear host genes were unchanged. CDR1as was markedly upregulated and showed the strongest discrimination among the other circRNAs, similarly to the circRNA_and circRNA/linear mRNA ratio_SCOREs. Indeed, circRNA_SCORE correlated positively with the intraplaque inflammatory in-plaque_SCORE, linking systemic signatures to local plaque biology. In plaque tissue, CDR1 mRNA was reduced while CDR1as was relatively preserved, yielding a higher CDR1as/CDR1 mRNA ratio in vulnerable lesions.

PBMC circRNAs-particularly CDR1as-show promise as noninvasive biomarkers of carotid plaque vulnerability and reflect plaque inflammatory status. Validation in independent cohorts and integration with imaging could enable improved preoperative risk stratification.