Extracellular circulating microRNAs (miRNAs) are currently a focus of interest as non-invasive biomarkers of cardiovascular pathologies, including coronary artery disease (CAD) and acute coronary syndromes (ACS): myocardial infarction with and without ST-segment elevation (STEMI and NSTEMI) and unstable angina (UA). However, the current data for some miRNAs are controversial and inconsistent, probably due to pre-analytical and methodological variances in different studies. In this work, we fulfilled the basic pre-analytical requirements provided for circulating miRNA studies for application to stable CAD and ACS research. We used quantitative PCR to determine the relative plasma levels of eight circulating miRNAs that are potentially associated with atherosclerosis. In a cohort of 136 adult clinic CAD patients and outpatient controls, we found that the plasma levels of miR-21-5p and miR-146a-5p were significantly elevated in ACS patients, and the level of miR-17-5p was decreased in ACS and stable CAD patients compared to both healthy controls and hypertensive patients without CAD. Within the ACS patient group, no differences were found in the plasma levels of these miRNAs between patients with positive and negative troponin, nor were any differences found between STEMI and NSTEMI. Our results indicate that increased plasma levels of miR-146a-5p and miR-21-5p can be considered general ACS circulating biomarkers and that lowered miR-17-5p can be considered a general biomarker of CAD.

The potential of extracellular circulating microRNAs (miRNAs) as non-invasive biomarkers of atrial fibrillation (AF) has been confirmed by a number of recent studies. However, the current data for some miRNAs are controversial and inconsistent, probably due to pre-analytical and methodological differences. In this work, we attempted to fulfill the basic pre-analytical requirements provided for circulating miRNA studies for application to paroxysmal atrial fibrillation (PAF) research. We used quantitative PCR (qPCR) to determine the relative plasma levels of circulating miRNAs expressed in the heart or associated with atrial remodeling or fibrillation with reported altered plasma/serum levels in AF: miR-146a-5p, miR-150-5p, miR-19a-3p, miR-21-5p, miR-29b-3p, miR-320a-3p, miR-328-3p, miR-375-3p, and miR-409-3p. First, in a cohort of 90 adult outpatient clinic patients, we found that the plasma level of miR-320a-3p was elevated in PAF patients compared to healthy controls and hypertensive patients without AF. We further analyzed the impact of medication therapies on miRNA relative levels and found elevated miR-320a-3p levels in patients receiving angiotensin-converting-enzyme inhibitors (ACEI) therapy. Additionally, we found that miR-320a-3p, miR-21-5p, and miR-146a-5p plasma levels positively correlated with the CHA2DS2-Vasc score and were elevated in subjects with CHA2DS2-Vasc ≥ 2. Our results indicate that, amongst the analyzed miRNAs, miR-320a-3p may be considered as a potential PAF circulating plasma biomarker, leading to speculation as to whether this miRNA is a marker of platelet state change due to ACEI therapy.

Non-coding RNAs reflect many biological processes in the human body, including athero-sclerosis. In a cardiology outpatient department cohort (N = 83), we aimed to compare the levels of circulating microRNAs in groups with vulnerable plaques (N = 22), stable plaques (N = 23) and plaque-free (N = 17) depending on coronary computed tomography angiography and to evaluate associations of microRNA levels with calculated cardiovascular risks (CVR), based on the SCORE2 (+OP), ACC/AHA, ATP-III and MESA scales. Coronary computed tomography was performed on a 640-slice computed tomography scanner. Relative plasma levels of microRNA were assessed via a real-time polymerase chain reaction. We found significant differences in miR-143-3p levels (p = 0.0046 in plaque-free vs. vulnerable plaque groups) and miR-181b-5p (p = 0.0179 in stable vs. vulnerable plaques groups). Analysis of microRNA associations with CVR did not show significant differences for SCORE2 (+OP) and ATPIII scales. MiR-126-5p and miR-150-5p levels were significantly higher (p < 0.05) in patients with ACC/AHA risk >10% and miR-145-5p had linear relationships with ACC/AHA score (adjusted p = 0.0164). The relative plasma level of miR-195 was higher (p < 0.05) in patients with MESA risk > 7.5% and higher (p < 0.05) in patients with zero coronary calcium index (p = 0.036). A linear relationship with coronary calcium was observed for miR-126-3p (adjusted p = 0.0484). A positive correlation with high coronary calcium levels (> 100 Agatson units) was found for miR-181-5p (p = 0.036). Analyzing the biological pathways of these microRNAs, we suggest that miR-143-3p and miR-181-5p can be potential markers of the atherosclerosis process. Other miRNAs (miR-126-3p, 126-5p, 145-5p, 150-5p, 195-5p) can be considered as potential cardiovascular risk modifiers, but it is necessary to validate our results in a large prospective trial.

Aim    To identify possible predictors of tachycardia-induced cardiomyopathy (TICMP) in patients with newly developed decompensated chronic heart failure (CHF) of nonischemic origin with reduced left ventricular ejection fraction (LV EF) and with persistent atrial tachyarrhythmias. Material and methods    This study included 88 patients with newly developed decompensated CHF of nonischemic origin with reduced LV EF and persistent atrial tachyarrhythmias. Resting 12-lead electrocardiography (EGC) and transthoracic echocardiography (EchoCG) were performed upon admission and following the electrical impulse therapy for all patients. Also, 24-h ECG monitoring was performed to confirm sinus rhythm stability. After recovery of sinus rhythm, outpatient monitoring was performed for three months, including repeated EchoCG to evaluate the dynamics of heart chamber dimensions and LV EF. Results    The patients were divided into two groups based on the increase in LV EF: 68 responders (TICMP patients with a LV EF increase by >10%) and 20 non-responders (patients with an increase in LV EF by <10% during 3 months following the sinus rhythm recovery). According to results of the baseline EchoCG, LV EF did not significantly differ in the two subgroups (TICMP, 40±8.3 %, 18–50 % and non-responders, 38.55±7.9 %, 24–50 %); moreover, the incidence of cases with LV EF <30% did not differ either (9 patients TICMP and 2 non-responders, р=1.0). TICMP patients compared to non-responders, had significantly smaller left atrial dimensions (4.53±1.14 (2–7) cm and 5.68±1.41 (4–8) cm, р=0.034; 80.8±28.9 (27–215) ml and 117.8±41.3 (46–230) ml, р=0.03, respectively) and left ventricular end-systolic volume (ESV) (67.7±33.1 (29–140) ml and 104.5±44.7 (26–172) ml, р=0.02, respectively). The effect of major EchoCG parameters on the probability of TICMP development was assessed by one-factor and multifactor regression analyses with adjustments for age and sex. The probability of TICMP increased with the following baseline EchoCG parameters: end-diastolic volume (EDV) <174 ml [odd ratio (OR), 0.115, 95 % confidence interval (CI): 0.035–0.371], ESV <127 ml [OR, 0.034, 95 % CI: 0.007–0.181], left atrial volume <96 ml [OR, 0.08 , 95 % CI: 0.023–0.274], right ventricular dimension <4 cm [OR, 0.042 , 95 % CI: 0.005–0.389].Conclusion    Among patients with newly developed decompensation of CHF with reduced LV EF of non-ischemic origin and persistent atrial arrhythmias, TICMP was detected in 72 % of patients. The probability of TICMP did not depend on baseline EF and duration of arrhythmias, but increased with the following baseline EchoCG parameters: EDV< 174 ml, ESV< 127 ml, left atrial volume <96 ml, right ventricular dimension <4 cm. The multifactorial analysis showed that a right atrial volume <96 ml is an independent predictor for the development of TICMP.

Rationale. Cardiovascular diseases remain the leading cause of human death in the world. Studying the role of regulatory non-coding RNAs, which include short single-stranded miRNA molecules, allows a more detailed understanding of the pathological processes underlying the progression of atherosclerosis. Objective to compare the levels of circulating miRNAs in patients with coronary heart disease, confirmed by multislice computed tomography-coronarography (MSCT-CA), with risks of cardiovascular complications and clinical and demographic characteristics. To compare the profiles of circulating miRNAs in groups of patients with stable and unstable atherosclerotic plaques. Methods. MicroRNA levels in the plasma of peripheral blood of patients with coronary heart disease were determined using the miScript miRNA PCR Array MIHS-105Z kit (Qiagen). The significance of differences in miRNA levels between the compared groups was determined using the MannWhitney U-test. The correlations of the levels of circulating miRNAs with clinical and demographic parameters were evaluated using the Spearman correlation coefficient. Risk assessment of cardiovascular complications in these patients was carried out using validated scales (ACC/AHA, Framinghm, SCORE, MESA). Atherosclerotic plaque stability was evaluated using MSCT-CA. Results. The study showed a significant (p 0.05) decrease in miR-16, miR-211, miR-195 miRNA levels in the plasma of patients with coronary heart disease, which correlated with an increase in cardiac vascular risk (CVR) according to ACC/AHA, Framingham and MESA. When comparing groups of patients with stable and unstable atherosclerotic plaques, the latter revealed an increase in the level of let-7b-5p circulating microRNA (p 0.05). Conclusion. Significant associations of the three studied microRNAs with the estimated risk of CVR were identified. It is important to find circulating let-7b-5p in a group of patients with unstable atherosclerotic plaques. Correlations were established between the levels of circulating microRNAs and clinical and demographic characteristics of patients. The study shows the involvement of some microRNAs in the regulation of atherosclerosis.