MiR-223-3p levels in the plasma and atherosclerotic plaques are increased in aged patients with carotid artery stenosis; association with HDL-related proteins

Abstract

Background: Cardiovascular diseases are still the main cause of death worldwide. Our aim was to analyse the link between miR-223-3p levels, dysfunctional HDL and the age of patients with carotid artery stenosis (CAS).

Methods and results: Thirty-two CAS patients enrolled for endarterectomy were divided in 2 groups: aged over 65 years (n = 19) and under 65 years (n = 13). Plasma samples and atherosclerotic plaques from the carotid artery were collected from all patients. Plaque levels of miR-223-3p and its primary transcript (pri-miR-223) were assessed, together with Drosha, Dicer, apolipoprotein (apo)A-I, apoE and myeloperoxidase (MPO) gene expression. In the plasma and plaques, miR-223-3p expression levels were significantly increased in CAS patients over 65 years. Positive correlations between plaque miR-223-3p and pri-miR-223 levels with Drosha, apoA-I and MPO expression were observed. Significantly increased miR-223-3p levels in the plasma of CAS patients over 65 years were measured. Significant correlations between plasma miR-223-3p levels and HDL-related proteins were determined. The variance of plasma miR-223-3p levels was predicted significantly by the multiple regression models using either age, clinical variables, blood lipids or oxidative and inflammatory parameters. Receiver operator characteristic analysis revealed that plasma miR-223-3p levels and HDL-related proteins (MPO activity/apoA-I ratio, MPO specific activity) were correlated with advanced age.

Conclusions: Taken together, these data suggest that plasma levels of miR-223-3p are independently associated with ageing in CAS patients and that, correlated with parameters associated with dysfunctional HDL, could predict the aggravation of CAS in elderly patients.

Keywords: Atherosclerosis; Carotid artery stenosis; Dysfunctional HDL; Pri-miRNA; miR-223-3p; microRNA.