Circulating microRNAs in Carotid Atherosclerosis: Complex Interplay and Possible Associations with Atherothrombotic
Marine M Tanashyan1, Alla A Shabalina2, Vladislav A Annushkin1
1Research Center of Neurology, 80, Volokolamskoe Shosse, 125367 Moscow, Russia.
Insights
Circulating microRNAs (miRs) show altered expression in patients with carotid atherosclerosis (CA) and a history of ischemic stroke. These miRs may serve as novel biomarkers for CA progression and stroke risk.
Area of Science:
- Cardiovascular Research
- Epigenetics
- Molecular Biology
Background:
- Atherosclerosis, particularly carotid atherosclerosis (CA), is a primary driver of cardiovascular disease and ischemic stroke.
- Epigenetic factors, including microRNAs (miRs), are implicated in CA pathogenesis, but their specific role in stroke remains unclear.
- Understanding circulating miR profiles in CA patients can offer insights into stroke risk and disease progression.
Purpose of the Study:
- To investigate the association between circulating microRNA expression profiles and symptomatic carotid atherosclerosis (CA) with a history of ischemic stroke.
- To identify specific miRs that are differentially expressed in CA patients with and without prior stroke.
- To explore the potential of these miRs as biomarkers for CA and stroke risk.
Main Methods:
- Plasma samples were collected from 81 patients with moderate-to-severe CA.
- Expression levels of 24 specific microRNAs were measured using quantitative real-time PCR.
- Statistical analyses, including multivariable logistic regression and cluster analysis, were performed to identify significant miR associations with stroke status.
Main Results:
- Several miRs, including miR-200c-3p, miR-106b-3p, and miR-494-5p, were upregulated in stroke survivors.
- Conversely, miR183-3p, miR-126-5p, and miR-216-3p showed lower plasma levels in symptomatic patients.
- Multivariable analysis identified miR-106b-5p, miR-183-3p, miR-216-3p, and miR-494-5p as significant predictors of symptomatic CA.
Conclusions:
- Circulating microRNA expression patterns differ between carotid atherosclerosis patients with and without a history of ischemic stroke.
- Specific miRs, such as miR-106b-5p, miR-183-3p, miR-216-3p, and miR-494-5p, are potential epigenetic biomarkers for CA progression and stroke.
- Further research into these miRs could lead to improved diagnostic and prognostic tools for cardiovascular and cerebrovascular diseases.
Abstract:
Atherosclerosis is a chronic inflammatory disorder which remains the main cause of cardiovascular morbidity and mortality, with carotid atherosclerosis (CA) being a major cause of ischemic stroke. Epigenetic regulation plays a significant role in CA progression and stroke, yet the impact of circulating microRNA expression, associated with atherogenesis, has not been clearly defined. We included 81 patients with moderate-severe CA (mean age 67 ± 7 years, 53% male), 42% of whom had prior ipsilateral ischemic stroke (i.e., were symptomatic). A total of 24 miRs were identified and their plasma expression levels were measured. We observed that several microRNAs were up-regulated in stroke survivors, namely miR-200c-3p (30.6 vs. 29.7, p = 0.047), miR-106b-3p (31.01 vs. 30.25, p = 0.004), and miR-494-5p (39 vs. 33, p < 0.001), while others (miR183-3p [25.5 vs. 28.6, p < 0.001], miR-126-5p [35.6 vs. 37.1, p = 0.03], and miR-216-3p [12.34 vs. 16.2, p < 0.001]) had lower plasma levels in symptomatic patients. In a multivariable logistic regression model for symptomatic CA, the only miRs showing statistical significance were miR-106b-5p, miR-183-3p, miR-216-3p, and miR-494-5p. Cluster analysis demonstrated differential miR expression in CA patients depending on their stroke status. Epigenetic modulation, represented as complex interplay between circulating miRs of different atherogenic potential, may play a significant role in CA development and progression. In our study, we show possible candidates for future research regarding CA and stroke.
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