MicroRNA and Hemostasis Profile of Carotid Atherosclerosis
Anton A Raskurazhev1, Polina I Kuznetsova1, Alla A Shabalina1
1Research Center of Neurology, 125367 Moscow, Russia.
Insights
Carotid atherosclerosis (CA) progression is linked to specific microRNA (miRNA) changes. MiR-126-5p downregulation indicates advanced CA, suggesting its potential as a biomarker for ischemic stroke risk.
Area of Science:
- Biochemistry
- Genetics
- Vascular Biology
Background:
- Carotid atherosclerosis (CA) is a significant risk factor for ischemic stroke.
- Understanding the molecular mechanisms, including microRNA (miRNA) profiles and hemostatic activation, is crucial for risk stratification.
Purpose of the Study:
- To characterize the miRNA and hemostasis profiles in patients with moderate and advanced carotid atherosclerosis.
- To explore potential correlations between miRNA expression and hemostatic activation in CA.
Main Methods:
- A prospective case-control study involving 61 patients with ultrasound-confirmed carotid atherosclerosis.
- Division of patients into moderate (<60% stenosis) and advanced (≥60% stenosis) groups.
- Analysis of general blood tests, hemostatic parameters, and miRNA quantification via RT-PCR.
Main Results:
- Distinct miRNA expression profiles were observed between moderate and advanced CA.
- Higher levels of miR-33a-5p/3p and lower levels of miR-126-5p were found in advanced CA.
- Significant correlations were identified between specific miRNAs (e.g., miR-29-3p, miR-21-5p) and hemostatic factors (e.g., Factor V, Factor VIII, ADAMTS13) in the moderate CA group.
Conclusions:
- Downregulation of miR-126-5p serves as a potential biomarker for advanced carotid atherosclerosis.
- The study suggests an interplay between miRNA expression and hemostatic activation in the progression of CA.
- Further research may elucidate the role of these miRNAs in stroke risk prediction.
Abstract:
Carotid atherosclerosis (CA) is an important risk factor for ischemic stroke. We described the miRNA and hemostasis profile of patients with moderate and advanced stages of carotid atherosclerosis and elucidated potential correlations with hemostatic activation. A prospective case-control study included 61 patients with evidence of carotid atherosclerosis (via ultrasound). The study population was divided into groups depending on the degree of carotid artery stenosis: 60% or more (advanced) and <60% (moderate). All patients underwent the following blood tests: general blood test, hemostatic parameters and microRNA. Extraction of microRNA was performed using Leukocyte RNA Purification Kit (NORGEN Biotec Corp., Thorold, ON, Canada); miRNA quantification was performed via RT-PCR. Statistical analysis was performed in R programming language (v. 4.1.0) using RSudio. MicroRNA expression profile was different depending on CA degree. MiR-33a-5p/3p levels were higher in patients with ≥60% carotid stenosis (42.70 and 42.45 versus 38.50 and 38.50, respectively, p < 0.05). Almost complete separation can be visualized with the levels of miR-126-5p: 9.50 in the moderate CA group versus 5.25 in the advanced CA (p < 0.001). MiR-29-5p was higher in the moderate CA group: 28.60 [25.50;33.05] than in advanced CA group: 25.75 [24.38;29.50] (p = 0.086); miR-29-3p was also higher in the moderate CA group: 10.36 [8.60;14.99] than in advanced CA group: 8.46 [7.47;10.3] (p = 0.001). By-group pairwise correlation analyses revealed at least three clusters with significant positive correlations in the moderate CA group: miR-29-3p with factors V and XII (r = 0.53 and r = 0.37, respectively, p < 0.05); miR-21-5p with ADAMTS13, erythrocyte sedimentation rate and D-dimer (r = 0.42, r = 0.36 and r = 0.44, respectively, p < 0.05); stenosis degree with miR-33a-5p/3p and factor VIII levels (r = 0.43 (both) and r = 0.62, respectively, p < 0.05). Hemostasis parameters did not reveal significant changes in CA patients: the only statistically significant differences concerned factor VIII, plasminogen and (marginally significant) ADAMTS-13 and protein C. Down-regulation of miR-126-5p expression has been identified as a promising biomarker of advanced carotid atherosclerosis with high specificity and sensitivity. Correlation cluster analysis showed potential interplay between miRNAs and hemostatic activation in the setting of carotid atherosclerosis.
