Abstract 36: Array-based Profiling Reveals Biomarker and Therapeutic Potential for Different microRNAs in Patients with Symptomatic Carotid Stenosis

Abstract

The discovery of an entirely new method of recognition and regulation of gene expression and protein translation by microRNAs (miRs) has provided new hope for innovative disease discovery and therapy. Research in recent years has assigned miRs a key regulatory role during various pathological processes. Lately, their potential as biomarkers in disease received a lot of attention. Aim of the present study was to explore the role of miRs as potential regulators and plasma biomarkers in patients with carotid stenosis and at risk of stroke. Utilizing patient material from the Biobank of Karolinska Endarterectomies (BiKE), we were able to profile the regulation of miRs in patients with asymptomatic vs. symptomatic carotid stenosis undergoing carotid endarterectomy. A PCR-based microRNA array of plasma, sampled at the carotid lesion site, identified eight miRs (miRs-15b, -29c, -30c/d, -150, -191, -210 and -500) being substantially altered in symptomatic vs. asymptomatic patients. In peripheral plasma samples, the expression of miRs-150 and -191 remained significantly different. Using an in vitro cell streamer system, we subjected human carotid smooth muscle cells, as well as human carotid endothelial cells, to physiologic and pathologic flow conditions. Interestingly and in accordance with our findings from the initial plasma profiling study, laminar (physiologic) flow induced miR-210 up-regulation, whereas turbulent (pathologic) flow suppressed miR-210 expression in both cell lines. In addition, similar significant changes in miR-210 regulation were detectable in a model of vascular remodelling, balloon injury of the carotid artery in Sprague Dawley rats. Of importance, miR-210 targets several key genes and signalling pathways involved in vascular remodelling and atherosclerotic plaque stability. The present study explores the diagnostic, prognostic and therapeutic potential of miR regulation in patients with symptomatic carotid stenosis and increased risk of stroke. We were able to identify miRs-150 and -191 as potential diagnostic plasma markers, and miR-210 as a key modulator of pathologic processes in atherosclerosis-related vascular remodelling.