Abstract 20036: Acute Carotid Plaque Rupture is Characterized by an Anti-Proliferative Serum miRNA Profile
Introduction: Atherosclerotic plaque vulnerability is mediated by thinning of the plaque’s fibrous cap. miRNAs play an important role in this transition of an atherosclerotic plaque from a stable to a vulnerable state. Release of miRNAs from advanced atherosclerotic plaques into the circulation may provide a measurable miRNA profile to identify patients at greatest risk of plaque rupture and stroke.
Hypothesis: Plaque destabilization and rupture are driven by anti-proliferative changes in microRNA expression within the plaque that can be detected in the sera of atherosclerosis patients.
Methods: Using RNA-Seq methodology, serum and atherosclerotic plaque microRNA content was compared between patients undergoing carotid endarterectomy (CEA) for 2 distinct clinical phenotypes: (1) patients without previous neurological events but high-grade carotid stenosis (asymptomatic), and (2) patients with an acute neurological event within 5 days of the CEA (urgent).
Results: A total of 695 miRNAs were detected in the sera with 22 miRNAs significantly decreased and 32 significantly increased in the sera of urgent compared to asymptomatic patients (adjusted p-value < 0.05). There was a positive correlation between the serum miRNA profile and that of the carotid plaque for 61% of the serum miRNAs. Gene ontology of the altered miRNAs targets showed enrichment for genes associated with proliferation that suggests an anti-proliferative phenotype in the urgent group, with repression of a network of pro-proliferative genes (Figure) and loss of repression of cell cycle inhibitors.
Conclusions: Carotid plaque rupture is associated with a unique serum miRNA profile that suggests an inhibition of proliferation. The majority of these miRNA changes are also exhibited within the atherosclerotic plaque. These circulating miRNAs are potential biomarkers for risk of carotid plaque rupture and stroke.
Author Disclosures: A.M. Brug: None. S. Smith: None. A.J. Brooks: None. D.J. Lightell: None. H.A. Bazan: None. T.C. Woods: None.
- © 2016 by American Heart Association, Inc.