Evaluation of microRNA Expression Features in Patients with Various Types of Arterial Damage: Thoracic Aortic Aneurysm and Coronary Atherosclerosis.

Circulating serum miRNA are increasingly used as biomarkers and potential treatment targets in several clinical scenarios, including cardiovascular diseases. However, the current data on circulating miRNA in thoracic aorta aneurism (TAA) patients are inconclusive. The aim of the present study is to compare the levels of several circulating miRNA in patients with degenerative TAA, coronary artery disease (CAD), and controls for special profile identification. We have identified several candidates for the role of new biomarkers: miR-143-3p, miR-181-5p, miR-126-3p, miR-126-5p, miR-145-5p, miR-150-5p, and miR-195-5p. MATERIALS AND METHODS: Serum samples of 100 patients were analyzed, including 388 TAA patients scheduled for elective surgery, 67 patients with stable CAD and 17 controls, were used for miRNA isolation and identification. RESULTS: More specific for TAA with very high predictive ability in ROC analysis was an increase in the levels of miR-21-5p, miR-29b-5p, miR-126-5p/-3p, miR-181b-5p, and miR-92a-3p, with the latter microRNA being investigated as a novel potential marker of TAA for the first time. CONCLUSION: TAA and CAD patients demonstrated a significant increase in the levels of circulating miR-126-5p/-3p, miR-181b-5p, and miR-29b-3p. More specific for TAA with very high predictive ability in ROC analysis was an increase in the levels of miR-21-5p, -29b-5p, -126-5p/-3p, 181b-5p, and -92a-3p, with the latter microRNA being investigated as a potential marker of TAA for the first time.

Diversity and Differential Expression of MicroRNAs in the Human Skeletal Muscle with Distinct Fiber Type Composition.

The ratio of fast- and slow-twitch fibers in human skeletal muscle is variable and largely determined by genetic factors. In this study, we investigated the contribution of microRNA (miRNA) in skeletal muscle fiber type composition. The study involved biopsy samples of the vastus lateralis muscle from 24 male participants with distinct fiber type ratios. The miRNA study included samples from five endurance athletes and five power athletes with the predominance of slow-twitch (61.6-72.8%) and fast-twitch (69.3-80.7%) fibers, respectively. Total and small RNA were extracted from tissue samples. Total RNA sequencing (N = 24) revealed 352 differentially expressed genes between the groups with the predominance of fast- and slow-twitch muscle fibers. Small RNA sequencing showed upregulation of miR-206, miR-501-3p and miR-185-5p, and downregulation of miR-499a-5p and miR-208-5p in the group of power athletes with fast-twitch fiber predominance. Two miRtronic miRNAs, miR-208b-3p and miR-499a-5p, had strong correlations in expression with their host genes (MYH7 and MYH7B, respectively). Correlations between the expression of miRNAs and their experimentally validated messenger RNA (mRNA) targets were calculated, and 11 miRNA-mRNA interactions with strong negative correlations were identified. Two of them belonged to miR-208b-3p and miR-499a-5p, indicating their regulatory links with the expression of CDKN1A and FOXO4, respectively.

Circulating Extracellular miRNA Analysis in Patients with Stable CAD and Acute Coronary Syndromes.

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.

Elevated Plasma Levels of Circulating Extracellular miR-320a-3p in Patients with Paroxysmal Atrial Fibrillation.

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.

Coronary heart disease diagnosis by artificial neural networks including genetic polymorphisms and clinical parameters.

The aim of this study was to develop an artificial neural networks-based (ANNs) diagnostic model for coronary heart disease (CHD) using a complex of traditional and genetic factors of this disease. The original database for ANNs included clinical, laboratory, functional, coronary angiographic, and genetic [single nucleotide polymorphisms (SNPs)] characteristics of 487 patients (327 with CHD caused by coronary atherosclerosis, 160 without CHD). By changing the types of ANN and the number of input factors applied, we created models that demonstrated 64-94% accuracy. The best accuracy was obtained with a neural networks topology of multilayer perceptron with two hidden layers for models included by both genetic and non-genetic CHD risk factors.