Identification of a molecular signature as potential biomarker in blood of symptomatic and asymptomatic patients with carotid atherosclerosis

Collura, Salvatore (2022) Identification of a molecular signature as potential biomarker in blood of symptomatic and asymptomatic patients with carotid atherosclerosis, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze chirurgiche, 34 Ciclo.
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Abstract

Background and Objectives: Carotid revascularization to prevent future vascular events is reasonable in patients with high-grade carotid stenosis. Currently, several biomarkers to predict carotid plaque development and progression have been investigated, among which microRNAs (miRs) are promising tools for the diagnosis of atherosclerosis. Methods and Results: A total of 49 participants were included in the study, divided into two main populations: Population 1 comprising symptomatic and asymptomatic inpatients, and Population 2 comprising asymptomatic outpatients. The study consisted of two main phases: a preliminary discovery phase and a validation phase, applying different techniques. MiR-profiles were performed on plasma and plaque tissue samples obtained from 4 symptomatic and 4 asymptomatic inpatients. MiRs emerging from profiling comparisons, i.e. miR-126-5p, miR-134-5p, miR-145-5p, miR-151a-5p, miR-34b, miR-451a, miR-720 and miR-1271-5p, were subjected to validation through RT-qPCR analysis in the total cohort of donors. Comparing asymptomatic and symptomatic inpatients, significant differences were reported in the expression levels of c-miRs for miR-126-5p and miR-1271-5p in blood, being more expressed in symptomatic subjects. In contrast, simultaneous evaluation of the selected miRs in plaque tissue samples did not confirm data obtained by the miR profiling, and no significant differences were observed. Using Receiver-Operating Characteristic (ROC) analysis, a circulating molecular signature (mir-126-5p, miR-1271-5p, albumin, C-reactive protein, and monocytes) was identified, allowing the distinction of the two groups in Population 1 (AUC = 0.795). Conclusions: Data emerging from this thesis suggest that c-miRs (i.e. miR-126-5p, miR-1271-5p) combined with selected haemato-biochemical parameters (albumin, C-reactive protein, and monocytes) produced a good molecular 'signature' to distinguish asymptomatic and symptomatic inpatients. C-miRs in blood do not necessarily reflect the expression levels of the same miRs in carotid plaque tissues since different mechanism can influence their expression.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Collura, Salvatore
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
34
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
Carotid Atherosclerosis MicroRNAs Biomarkers
URN:NBN
Data di discussione
17 Giugno 2022
URI

Altri metadati

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