Plasma-Derived Exosomal Circular RNA hsa_circ_0005540 as a Novel Diagnostic Biomarker for Coronary Artery Disease

Abstract

Background. Exosomes exist in almost all body fluid and contain diverse biological contents which may be reflective of disease state. Circular RNAs (circRNAs) are stable in structure and have a long half-life in exosomes without degradation, thus making them reliable biomarkers. However, the potential of exosomal circRNAs as biomarkers of coronary artery disease (CAD) remains to be established. Here, we aimed to investigate the expression levels and the potential use of exosomal circRNAs as diagnostic biomarkers for CAD. Methods. CircRNA expression levels in exosomes obtained from three plasma samples of CAD patients and three paired controls were analyzed using RNA sequencing. Exosomal circRNAs obtained in the profiling phase were then verified in two-center validation cohorts. Finally, the ability of exosomal circRNAs, adjusting for Framingham Heart Study (FHS) risk factors, was determined to discriminate between CAD patients and non-CAD controls. Results. 355 circRNAs were differentially expressed between these two groups: 164 were upregulated, and 191 were downregulated. Here, we selected the potential circRNAs (fold change>4, P<0.05) as candidate biomarkers for further validation. Our data showed that only hsa_circ_0005540 was significantly associated with CAD (P<0.0001). After adjustment for risk factors, hsa_circ_0005540 showed a high discriminatory power for CAD in ROC analyses (AUC=0.853; 95%confidence interval CI=0.799−0.906, P<0.001). Conclusion. Our results suggest that plasma exosomal hsa_circ_0005540 can be used as a promising diagnostic biomarker of CAD.

Circulating Circular RNAs: Novel Biomarkers for Heart Failure

“…Has_circ_0005540 was selected from 355 circRNAs, which had a remarkably fold change and associated with CAD. (Wu et al, 2020) has_circ_0097435 ↑ Plasma HF (n=45) Healthy volunteer (n=44)…”

“…Cardiac ischemia/reperfusion (I/R) could increase the secretion of EVs; the following RNA-seq of EVs identified 185 significantly differentially expressed circRNAs, 119 downregulated and 66 upregulated, compared with the sham, suggesting that circRNAs in cardiac EVs might indicate development of I/R as biomarkers (Ge et al, 2019). Using circRNAs to improve the discriminatory power for CVD has been discussed (Wu et al, 2020). Exosmal circRNA expression levels in exosomes was analyzed from 3 plasma samples of CAD patients and 3 paired controls using RNA sequencing.…”

The Role of Exosomal Non-Coding RNAs in Coronary Artery Disease

“…It was speculated that exosome lncRNA HIF1A-AS1 could be used as a potential biomarker of AS (Wang et al, 2017). Another study analyzed circRNA expression in plasma exosomes from patients with CAD and controls using RNA sequencing and found that plasma exosomal hsa_circ_0005540 could be a promising biomarker for the diagnosis of CAD (Wu et al, 2020).…”

Non-Coding RNAs as Blood-Based Biomarkers in Cardiovascular Disease

“…In fact, augmented circSMARCA5 levels are associated with a decreased segment stenosis score as well as with decreased cardiovascular risk [58]. Furthermore, RNA sequencing from plasma exosomes of CAD and non-CAD patients identified 335 exosomal circRNAs to be differentially expressed among the two groups [59]. After adjusting for risk factors, circ0005540 was upregulated in CAD patients, and displayed high sensitivity and specificity for identifying CAD patients, suggesting its potential as a CAD biomarker [59].…”