Abstract 14779: Array-Based Profiling Reveals Biomarker and Therapeutic Potential for Different MicroRNAs in Patients With Symptomatic Carotid Stenosis
Recognition and regulation of gene expression and protein translation by microRNAs (miRs) has the potential of revolutionizing vascular disease discovery and therapy. Aim of the present study was to explore the therapeutic and biomarker role of miRs in patients with carotid stenosis at risk of stroke.
Utilizing patient material from the Biobank of Karolinska Endarterectomies (BiKE), we were able to profile miR expression in patients with symptomatic vs. asymptomatic carotid stenosis. A PCR-based miR array of plasma, sampled at the carotid lesion site, identified eight significantly up- or down-regulated miRs (miR-15b, -29c, -30c/d, -150, -191, -210 and -500) in symptomatic vs. asymptomatic patients. In peripheral plasma samples, only miR-150 and miR-191 remained significantly altered. Using an in vitro cell streamer system, we subjected human carotid arterial smooth muscle cells and endothelial cells to physiologic (laminar) vs. pathologic (turbulent/oscillatory) flow conditions. Out of the eight miRs identified in our plasma array, two showed a significant difference in expression (down-regulation of miR-210 and up-regulation of miR-15b). In addition, similar significant changes in miR-210 and miR-15b regulation were detectable in two rodent models of vascular remodelling (balloon injury of the carotid artery in Sprague Dawley rats) and plaque vulnerability (carotid ligation/cuff injury in apoE-/- mice). miR-210 has been identified to target several key genes and signalling pathways in vascular disease pathology. The most prominently regulated target of miR-210 in our studies was thrombospondin-1 (THBS1).
In this currently presented study, we were able to detect miRs showing a disease modulatory (miRs-210 and -15b) and biomarker potential (miRs-150 and -191) in patients with symptomatic carotid stenosis at risk of stroke. Our current research is focused on using miR modulation to enhance plaque stability and vascular remodelling to prevent plaque rupture.
- © 2013 by American Heart Association, Inc.