Circulating MiRNA-195-5p and -451a in Transient and Acute Ischemic Stroke Patients in an Emergency Department.

Lorenzo Malatino,Alessandra Di Sette,Tiziana Ciarambino,Luigi Adinolfi,Michele D’Amico,Maria Trotta,Raffaele Marfella,Mauro Giordano,Giuseppe Paolisso

doi:10.3390/jcm8020130

Abstract

We have evaluated circulating miRNAs (-195-5p and -451a) in subjects with acute ischemic stroke (AIS) and in patients with transient ischemic attack (TIA). In this study, 18 subjects with AIS and 18 patients with TIA were enrolled and examined at admission (T0) and at 24 h and 48 h after admission, and compared to 20 controls (C). At T0, circulating miRNA-195-5p and -451a were significantly upregulated in both AIS and TIA patients, compared to C. We also observed a progressive reduction of circulating miRNA levels at 24 h and 48 h in both AIS and TIA patients. Hypoxia inducible factor 1alpha (HIF-1α) serum level was significantly increased at T0, in both AIS and TIA patients, in comparison to C (both p < 0.01 vs. C) and it decreased in both AIS and TIA patients at 24 h and at 48 h, in comparison to T0 (both p < 0.01 vs. T0). Vascular endothelial growth factor (VEGF) serum level was significantly decreased at T0, in both AIS and TIA patients, if compared to C (both p < 0.01 vs. C) and increased, in both AIS and TIA patients, at 24 h and 48 h, if compared to T0 (both p < 0.01 vs. T0). The elevated expression of miRNA-195-5p and miRNA-451a significantly decreased over time at 24 h and 48 h, and it is associated with decreased HIF-α levels and increased VEGF serum levels. These data may suggest a role for this miRNAs as biomarker in the pathogenesis and prognosis of AIS patients and for the first time also in TIA patients.

Highlights

Acute ischemic stroke (AIS) is one of the main causes of mortality and morbidity worldwide [1]
AIS was defined as an episode of acute neurological dysfunction caused by focal cerebral ischemia, based on objective imaging techniques such as computed tomography scan (CT) or magnetic resonance imaging scan (MRI) and clinical evidence of cerebral focal ischemic injury based on symptoms of any duration
transient ischemic attack (TIA) was defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction [34]

Summary

Introduction

Acute ischemic stroke (AIS) is one of the main causes of mortality and morbidity worldwide [1]. The stroke pathophysiology in the acute phase involves oxidative stress, inflammatory response, mitochondrial dysfunction, energy failure, activation of glial cells, disruption of the blood–brain barrier (BBB) and changes in microRNA (miRNAs) expression [4] These endogenous noncoding short single-stranded RNAs have recently emerged as essential gene regulators for the orchestration of brain development and function [5,6,7,8,9,10,11]. It has never been correlated to the angiogenesis of ischemic stroke Since this process is crucial, to restore the blood flow to the ischemic area, and to promote neurogenesis and to improve neurological functions [29], miR-195-5p and miR-451a could be an important therapeutic target for AIS. In this observational study we evaluate the expression of circulating miR-195-5p and miR-451a in both AIS and TIA patients in comparison with control subjects, in order to verify if they could be valuable biomarkers for rapid diagnosis and prognosis of ischemic stroke, as well as promising therapeutic agents

Patients Enrollment and Inclusion Criteria

Serum HIF-1α and VEGF-A ELISA Assays

Statistical Analysis

MiRNAs Timing in AIS and TIA Patients

VEGF in AIS and TIA Patients

Discussion

Limitations