Circulating Exosomal circRNAs Contribute to Potential Diagnostic Value of Large Artery Atherosclerotic Stroke

Abstract

Large artery atherosclerotic (LAA) stroke is closely associated with atherosclerosis, characterized by the accumulation of immune cells. Early recognition of LAA stroke is crucial. Circulating exosomal circRNAs profiling represents a promising, noninvasive approach for the detection of LAA stroke. Exosomal circRNA sequencing was used to identify differentially expressed circRNAs between LAA stroke and normal controls. From a further validation stage, the results were validated using RT-qPCR. We then built logistic regression models of exosomal circRNAs based on a large replication stage, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic efficacy. Using exosomal circRNA sequencing, large sample validation, and diagnostic model construction revealed that exosomal circ_0043837 and circ_ 0001801were independent predictive factors for LAA stroke, and had better diagnostic efficacy than plasma circRNAs. In the atherosclerotic group (AS), we developed a nomogram for clinical use that integrated the two-circRNA-based risk factors to predict which patients might have the risk of plaque rupture. Circulating exosomal circRNAs profiling identifies novel predictive biomarkers for the LAA stroke and plaque rupture, with superior diagnostic value than plasma circRNAs. It might facilitate the prevention and better management of this disease.

Exosomes in atherosclerosis: Convergence on macrophages

“…Similar results were found in another study based on exosomal circRNA. Our experiment showed that exosomal circRNA could be used as a more efficient diagnostic marker for LAA stroke; much more interestingly, we found that exosomal circRNA could predict vulnerable plaques 153 . Our studies have demonstrated the potential of exosomal non-coding RNAs as biomarkers.…”

Lnc_000048 Promotes Histone H3K4 Methylation of MAP2K2 to Reduce Plaque Stability by Recruiting KDM1A in Carotid Atherosclerosis

“…RNA isolation and quantification were carried out as previously described [26]. The Supplementary Materials went into detail about these specifics and Methods and primers used for the genes of interest are listed in Supplementary Table S1.…”

“…To assess H3K4me2, Chromatin immunoprecipitation (ChIP) assays were carried out in accordance with the manufacturer's instructions (26,156; Thermo Scientific) [29]. The details were described in the Supplementary Materials and Methods and primers used for the genes of interest are listed in Supplementary Table S3.…”

A Novel Perspective on Ischemic Stroke: A Review of Exosome and Noncoding RNA Studies

“…The nomogram also revealed the potential predictive value of exosomal circRNAs in plaque instability. Besides this, they suggested that these two exo-circRNAs exerted a protective role in ischemic stroke, as a negative correlation between their expression and the NIHSS scores was found [ 21 ]. Considering that this was a single-center study, future multicenter studies are needed to validate these results and avoid selective bias.…”