Abstract 123: Recently Ruptured Carotid Plaques Have Increased Levels of Circular RNA-16, Which Negatively Regulates the Proproliferative and Antiapoptotic MicroRNA-221: A Novel Mediator of Carotid Plaque Rupture
Objectives: Circular RNAs (circRNAs) are dynamically expressed during development and possess binding sites for microRNAs (miRs), small RNAs that negatively regulate gene expression. We recently demonstrated that miR-221, which is associated with VSMC proliferation and inhibition of apoptosis, is decreased in acutely symptomatic carotid plaques. As circRNA-16 possesses binding sites for miR-221 thru seed sequences found within, we hypothesized that circRNA-16 is increased in acutely symptomatic compared to asymptomatic carotid plaques.
Methods: Relative changes in gene expression levels of circRNA-16 were compared using a real-time PCR assay and the ΔΔCt method. All samples were run in duplicate; mean/standard error were calculated. One-way ANOVA with Tukey’s test was used to determine significance between groups.
Results: Expression of circRNA-16 was confirmed in human VSMC using PCR and resistance to RNAse H. To investigate its role in carotid plaque rupture, levels of circRNA-16 and miR-221 were quantified in patients undergoing urgent CEA for acute neurologic symptoms (n=27), with a mean duration of symptom onset to CEA of 2.4 days, compared to asymptomatic carotid plaques (n=19). In contrast to miR-221, circRNA-16 is increased in the urgent group compared to the asymptomatic carotid plaque group (Figure; 1.51±.26 vs. 1.00±.10, p=.03).
Conclusions: We demonstrate circRNA-16 levels are increased and miR-221 levels decreased in acutely ruptured carotid plaques. Furthermore, our data suggest that a circRNA-16/miR-221 axis may be important in fibrous cap degradation and rupture during the transition from a stable to an unstable carotid atherosclerotic plaque.
Author Disclosures: H.A. Bazan: None. D. Lightell: None. W. Sternbergh III: None. T. Woods: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.