Background: Obstructive sleep apnea syndrome (OSAS) is one of the most common sleep-related breathing disorders. The aim of this study was to improve diagnostics in OSAS using blood circulating biomarkers. We consider the potential of cardiac-specific miRNAs in the diagnosis and risk assessment of cardiovascular complications. Materials & methods: Plasmatic levels of miR-1-3p, miR-133a-3p and miR-499a-5p were measured by reverse transcription-PCR and compared with the clinical status of OSAS patients and controls. Results: The level of miR-499 was higher (p = 0.0343) in OSAS patients (mean expression: 0.00561) compared with the controls (mean expression: 0.00003), using the multivariate logistic regression. Conclusion: The role of miR-499 in gene expression regulation during hypoxia and our findings indicate that miR-499 could be a new diagnostic biomarker for OSAS.

• Klíčová slova
• biomarker, cardiovascular disease, miR1, miR133a, miR499, miRNA, sleep apnea syndrome,
• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• mikro RNA genetika   MeSH
• multivariační analýza MeSH
• obstrukční spánková apnoe krev   diagnóza   genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulace genové exprese MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• mikro RNA MeSH
• MIRN499 microRNA, human MeSH Prohlížeč

Proper muscle function constitutes a precondition for good heath and an active lifestyle during an individual's lifespan and any deviations from normal skeletal muscle development and its functions may lead to numerous health conditions including e.g. myopathies and increased mortality. It is thus not surprising that there is an increasing need for understanding skeletal muscle developmental processes and the associated molecular pathways, especially as such information could find further uses in therapy. The understanding of complex skeletal muscle developmental networks was broadened with the discovery of microRNA (miRNA) molecules. MicroRNAs are evolutionary conserved small non-coding RNAs capable of negatively regulating gene expression on a post-transcriptional level by means of miRNA-mRNA interaction. Several miRNAs expressed exclusively in muscle have been labeled myomiRs. MyomiRs represent an integral part of skeletal muscle development, i.e. playing a significant role during skeletal muscle proliferation, differentiation and regeneration. The purpose of this review is to provide a summary of current knowledge regarding the involvement of myomiRs in the individual phases of myogenesis and other aspects of skeletal muscle biology, along with an up-to-date list of myomiR target genes and their functions in skeletal muscle and miRNA-related therapeutic approaches and future prospects.

• Klíčová slova
• miR-1, miR-133, miR-206, miR-208b, miR-486, miR-499,
• MeSH
• kosterní svaly embryologie   metabolismus   MeSH
• lidé MeSH
• mikro RNA fyziologie   MeSH
• vývoj svalů * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN1 microRNA, human MeSH Prohlížeč
• MIRN133 microRNA, human MeSH Prohlížeč
• MIRN206 microRNA, human MeSH Prohlížeč
• MIRN486 microRNA, human MeSH Prohlížeč
• MIRN499 microRNA, human MeSH Prohlížeč

BACKGROUND: The evaluation of the long-term risk of major adverse cardiovascular events and cardiac death in patients after acute myocardial infarction (AMI) is an established clinical process. Laboratory markers may significantly help with the risk stratification of these patients. Our objective was to find the relation of selected microRNAs to the standard markers of AMI and determine if these microRNAs can be used to identify patients at increased risk. METHODS: Selected microRNAs (miR-1, miR-133a, and miR-499) were measured in a cohort of 122 patients from the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI treated with primary percutaneous coronary intervention (pPCI)). The cohort was split into two subgroups: 116 patients who did not die (survivors) and 6 patients who died (nonsurvivors) during the 365-day period after AMI. Plasma levels of selected circulating miRNAs were then assessed in combination with high-sensitivity cardiac troponin T (hsTnT) and N-terminal probrain natriuretic peptide (NT-proBNP). RESULTS: miR-1, miR-133a, and miR-499 correlated positively with NT-proBNP and hsTnT 24 hours after admission and negatively with left ventricular ejection fraction (LVEF). Both miR-1 and miR-133a positively correlated with hsTnT at admission. Median relative levels of all selected miRNAs were higher in the subgroup of nonsurvivors (N = 6) in comparison with survivors (N = 116), but the difference did not reach statistical significance. All patients in the nonsurvivor subgroup had miR-499 and NT-proBNP levels above the cut-off values (891.5 ng/L for NT-proBNP and 0.088 for miR-499), whereas in the survivor subgroup, only 28.4% of patients were above the cut-off values (p = 0.001). CONCLUSIONS: Statistically significant correlation was found between miR-1, miR-133a, and miR-499 and hsTnT, NT-proBNP, and LVEF. In addition, this analysis suggests that plasma levels of circulating miR-499 could contribute to the identification of patients at increased risk of death during the first year after AMI, especially when combined with NT-proBNP levels.

• MeSH
• biologické markery analýza   MeSH
• dospělí MeSH
• infarkt myokardu farmakoterapie   genetika   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• míra přežití MeSH
• následné studie MeSH
• prognóza MeSH
• regulace genové exprese u nádorů * MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• biologické markery MeSH
• mikro RNA MeSH
• MIRN1 microRNA, human MeSH Prohlížeč
• MIRN133 microRNA, human MeSH Prohlížeč
• MIRN499 microRNA, human MeSH Prohlížeč

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.

• MeSH
• bipolární porucha genetika   MeSH
• celogenomová asociační studie statistika a číselné údaje   MeSH
• genetická predispozice k nemoci genetika   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• modely nemocí na zvířatech MeSH
• potkani Sprague-Dawley MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA MeSH

This study aimed to evaluate the ability of selected microRNAs as biomarkers of atrial fibrillation (AF) in ischemic stroke patients in comparison with other established biochemical biomarkers. A prospective case-control study of consecutive ischemic stroke patients with AF admitted to a comprehensive stroke center was conducted. The control group consisted of patients with ischemic stroke with no AF detected on prolonged (at least 3 weeks) Holter ECG monitoring. As potential biomarkers of AF, we analyzed the plasma levels of microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) and 13 biochemical biomarkers at admission. The predictive accuracy of biomarkers was assessed by calculating the area under the receiver operating characteristic curve. The data of 117 patients were analyzed (61 with AF, 56 with no AF, 46% men, median age 73 years, median National Institutes of Health Stroke Scale 6). Biochemical biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and total triglycerides) were significantly associated with AF. NT-proBNP had the best diagnostic performance for AF with area under the receiver operating characteristic curve 0.92 (95%, CI 0.86-0.98); a cutoff value of >528 ng/L had a sensitivity of 79% and a specificity of 97%. None of the other biomarkers, including microRNAs, was associated with AF. Conventional biochemical biomarkers (NT-proBNP, high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and triglycerides), but not microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) were significantly associated with AF in our ischemic stroke cohort.

• MeSH
• biologické markery * krev   MeSH
• C-reaktivní protein analýza   MeSH
• fibrilace síní * krev   diagnóza   genetika   MeSH
• ischemická cévní mozková příhoda * krev   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * krev   MeSH
• natriuretický peptid typu B krev   MeSH
• peptidové fragmenty krev   MeSH
• prospektivní studie MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• biologické markery * MeSH
• C-reaktivní protein MeSH
• mikro RNA * MeSH
• natriuretický peptid typu B MeSH
• peptidové fragmenty MeSH
• pro-brain natriuretic peptide (1-76) MeSH Prohlížeč

A number of microRNAs are involved in the pathophysiological events associated with heart disease. In this review, we discuss miR-21, miR-1, miR-23a, miR-142-5p, miR-126, miR-29, miR-195, and miR-499 because they are most often mentioned as important specific indicators of myocardial hypertrophy and fibrosis leading to heart failure. The clinical use of microRNAs as biomarkers and for therapeutic interventions in cardiovascular diseases appears highly promising. However, there remain many unresolved details regarding their specific actions in distinct pathological phenomena. The introduction of microRNAs into routine practice, as part of the cardiovascular examination panel, will require additional clinically relevant and reliable data. Thus, there remains a need for additional research in this area, as well as the optimization and standardization of laboratory procedures which could significantly shorten the determination time, and make microRNA analysis simpler and more affordable. In this review, we aim to summarize the current knowledge about selected microRNAs related to heart failure, including their potential use in diagnosis, prognosis, and treatment, and options for their laboratory determination.

• Klíčová slova
• heart failure, miREIA, miRNA therapeutics, microRNA, two-tailed-qPCR,
• MeSH
• biologické markery MeSH
• fibróza MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• prognóza MeSH
• srdeční selhání * diagnóza   genetika   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• mikro RNA * MeSH

Cardiac muscle-related microRNAs play important roles in cardiac development and disease by translational silencing of mRNAs, the dominant mechanism of microRNA action. To test whether they could be involved in daunorubicin-associated cardiomyopathy (DACM), we determined expression patterns of myomiRs in two distinct models of DACM. We used 10-12 weeks old male Wistar rats. In the sub-acute model, rats were administered with six doses of daunorubicin (DAU-A, 3 mg/kg, i.p., every 48 h). Rats were sacrificed two days after the last dose. In the sub-chronic model, anaesthetized rats were administered a single dose of daunorubicin (15 mg/kg, i.v., DAU-C). Age-matched controls (CON) received vehicle. Rats were sacrificed eight weeks later. Left ventricular (LV) functions (LV pressure, rate of pressure development, +dP/dt and decline, -dP/dt) were measured using left ventricular catheterization. Expressions of myomiRs (miR-208a, miR-499, miR-1 and miR-133a), markers of cardiac failure (atrial and brain natriuretic peptides genes; Nppa and Nppb) and myosin heavy chain genes (Myh6, Myh7, Myh7b) in cardiac tissue were determined by RT-PCR. Protein expression of gp91phox NADPH oxidase subunit was detected by immunoblotting. Both DAU groups exhibited a similar depression of LV function, and LV weight reduction, accompanied by an upregulation of natriuretic peptides, and a decrease of Myh6 to total Myh ratio (-18% in DAU-A and - 25% in DAU-C, as compared to controls; both P < 0.05). DAU-C, but not DAU-A rats had a 35% mortality rate and exhibited a significantly increased gp91phox expression (DAU-C: 197 ± 33 versus CON-C: 100 ± 11; P < 0.05). Interestingly, myomiRs levels were only reduced in DAU-C compared to CON-C (miR-208: -45%, miR-499: -30%, miR-1: -29%, miR- and miR133a: -25%; all P < 0.05) but were unaltered in DAU-A. The lack of myomiRs expression, particularly in sub-chronic model, suggests the loss of control of myomiRs network on late progression of DACM. We suppose that the poor inhibition of mRNA targets might contribute to chronic DACM.

• Klíčová slova
• Anthracycline, Cardiomyopathy, Gene expression, MicroRNA, Myosin heavy chain isoforms, NADPH oxidase,
• MeSH
• daunomycin škodlivé účinky   farmakologie   MeSH
• down regulace účinky léků   MeSH
• kardiomyopatie chemicky indukované   metabolismus   patologie   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• mikro RNA biosyntéza   MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• svalové proteiny biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• daunomycin MeSH
• mikro RNA MeSH
• svalové proteiny MeSH

We sought to analyse plasma levels of peripheral blood microRNAs (miRs) as biomarkers of ST-segment-elevation myocardial infarction (STEMI) due to type-1 myocardial infarction as a model situation of vulnerable plaque (VP) rupture. Samples of 20 patients with STEMI were compared both with a group of patients without angina pectoris in whom coronary angiogram did not reveal coronary atherosclerotic disease (no coronary atherosclerosis-NCA) and a group of patients with stable angina pectoris and at least one significant coronary artery stenosis (stable coronary artery disease-SCAD). This study design allowed us to identify miRs deregulated in the setting of acute coronary artery occlusion due to VP rupture. Based on an initial large scale miR assay screening, we selected a total of 12 miRs (three study miRs and nine controls) that were tested in the study. Two of the study miRs (miR-331 and miR-151-3p) significantly distinguished STEMI patients from the control groups, while ROC analysis confirmed their suitability as biomarkers. Importantly, this was observed in patients presenting early with STEMI, even before the markers of myocardial necrosis (cardiac troponin I, miR-208 and miR-499) were elevated, which suggests that the origin of miR-331 and miR-151-3p might be in the VP. In conclusion, the study provides two novel biomarkers observed in STEMI, which may be associated with plaque rupture.

• MeSH
• akutní koronární syndrom genetika   MeSH
• genetické markery genetika   MeSH
• infarkt myokardu s elevacemi ST úseků genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• nemoci koronárních tepen genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• genetické markery MeSH
• mikro RNA MeSH
• MIRN151a microRNA, human MeSH Prohlížeč
• MIRN331 microRNA, human MeSH Prohlížeč