Abstract 19085: Circulating Long Noncoding RNA Signature Predicts Internal Carotid Artery Stenosis and Associated Cerebral Ischemia
Introduction: Internal carotid artery stenosis (ICAS) can lead to cerebral ischemia. Stress image studies have limited sensitivity to detect cerebral ischemia caused by ICAS. Currently, there are no biomarkers for ICAS and associated cerebral ischemia, precluding early intervention before clinical events occur. This study aimed to test the hypothesis that circulating long non-coding RNAs (lncRNAs) can be a useful biomarker to detect ICAS and associated cerebral ischemia.
Methods: Cell free, circulating lncRNA profiling was conducted using plasma RNA from subjects with significant (>70%) ICAS with cerebral ischemia on perfusion scan (n=14), significant ICAS without cerebral ischemia (n=8), coronary artery disease (CAD) without ICAS (n=8), and healthy subjects without CAD or ICAS (n=7), by RNA sequencing.
Results: A total of 127 million sequencing reads were obtained from 37 plasma RNA samples. Among the detected 1243 lncRNAs, 17 (14 up, 3 down) and 38 (all down) were significantly dysregulated with CAD and ICAS, respectively. Hierarchical clustering analysis revealed that plasma lncRNA profile discriminates ICAS from CAD and control samples. Among the 38 dysregulated lncRNAs with ICAS (ICAS lncRNA), only 3% were similarly dysregulated with CAD. Pathway analysis of ICAS lncRNAs based on their nearby mRNAs (cis-mRNA) showed significant enrichment of genes involved in cell junction dynamics and lipoid acid metabolism, both of which have been implicated in the pathogenesis of carotid atherosclerosis. Analysis on an independent microarray dataset obtained from the carotid arterial plaques from 32 hypertensive patients and paired normal arterial tissues from the same subjects (GSE43292) revealed that 24% (9 out of 38) of the cis-mRNA of the ICAS lncRNAs were similarly dysregulated in carotid arterial plaques, suggesting that circulating RNA expression can mirror, at least in part, the transcriptomal changes in atherosclerotic carotid lesions. Finally, lncRNA lnc-BMP2K-3:1 could discriminate between ICAS patients with and without cerebral ischemia (ROC curve AUC 0.73, p=0.02).
Conclusion: Circulating lncRNAs reflect the disease states of carotid atherosclerosis and could serve as a novel biomarker to detect ICAS and associated cerebral ischemia.
Author Disclosures: C. Yeh: None. Y. Chen: None. M. Lin: None. H. Kao: None. K. Yang: None.
- © 2016 by American Heart Association, Inc.