Circular RNAs: Biogenesis, Functions, and Role in Myocardial Hypertrophy.

Circular RNAs (circRNAs) are a large class of endogenous single-stranded covalently closed RNA molecules. High-throughput RNA sequencing and bioinformatic algorithms have identified thousands of eukaryotic circRNAs characterized by high stability and tissue-specific expression pattern. Recent studies have shown that circRNAs play an important role in the regulation of physiological processes in the norm and in various diseases, including cardiovascular disorders.

[The levels of certain circulating microRNAs in hypertrophic cardiomyopathy are associated with echocardiographic parameters].

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease; it is characterized by left ventricular (LV) hypertrophy that cannot be explained by hemodynamic causes. It is believed that sarcomere dysfunction underlies the pathogenesis of this disease, however, only half of patients with the HCM phenotype have mutations in sarcomere-encoding genes. HCM is distinguished by both high genetic and clinical heterogeneity and therefore more studies are seeking to investigate a regulation of gene expression in HCM and how the abnormalities in this process can affect disease phenotype.

Shared genetic architecture of COVID-19 and Alzheimer's disease.

The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the сoronavirus disease 2019 (COVID-19) have become a global health threat. At the height of the pandemic, major efforts were focused on reducing COVID-19-associated morbidity and mortality. Now is the time to study the long-term effects of the pandemic, particularly cognitive impairment associated with long COVID.

Advanced searching for hypertrophic cardiomyopathy heritability in real practice tomorrow.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease associated with morbidity and mortality at any age. As studies in recent decades have shown, the genetic architecture of HCM is quite complex both in the entire population and in each patient. In the rapidly advancing era of gene therapy, we have to provide a detailed molecular diagnosis to our patients to give them the chance for better and more personalized treatment.

Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease; its pathogenesis is still being intensively studied to explain the reasons for the significant genetic and phenotypic heterogeneity of the disease. To search for new genes involved in HCM development, we analyzed gene expression profiles coupled with DNA methylation profiles in the hypertrophied myocardia of HCM patients. The transcriptome analysis identified significant differences in the levels of 193 genes, most of which were underexpressed in HCM.

Vasovagal Syncope Is Associated with Variants in Genes Involved in Neurohumoral Signaling Pathways.

Vasovagal syncope (VVS) is the most common cause of sudden loss of consciousness. VVS results from cerebral hypoperfusion, due to abnormal autonomic control of blood circulation, leading to arterial hypotension. It is a complex disease, and its development is largely associated with genetic susceptibility.

[Expression analysis of miRNAs from the DLK1-DIO3 locus in CD4+ and CD14+ cells in patients with relapsing-remitting multiple sclerosis].

Objective: To analyze the expression of several previously unstudied miRNAs from the locus in peripheral blood mononuclear cells (PBMC) and in CD14 and CD4 cell subpopulations in patients with relapsing-remitting multiple sclerosis (RRMS) and healthy individuals.

Material And Methods: MiRNA expression analysis was performed in PBMC, CD14, and CD4 cells of 14 patients who did not take immunomodulatory drugs, and 14 individuals without autoimmune and inflammatory diseases by reverse transcription followed by real-time PCR.

Results: Expression levels of 10 miRNAs selected based on different criteria were significantly higher in PBMC in men with RRMS compared to healthy men; in women, their expression did not change in a similar comparison.

Male-specific coordinated changes in expression of miRNA genes, but not other genes within the DLK1-DIO3 locus in multiple sclerosis.

The role of miRNAs, small non-coding regulatory RNAs, in the molecular mechanisms of multiple sclerosis (MS) development has been intensively studied. MiRNAs tend to be clustered within imprinted regions, and the largest number of miRNA genes is observed in the DLK1-DIO3 locus. Earlier using RNA-seq we identified sex-specific upregulation of the set of miRNA genes from this locus in peripheral blood mononuclear cells (PBMC) of treatment-naive relapsing-remitting MS (RRMS) patients.

[MiRNA miR-375 as a Multifunctional Regulator of the Cardiovascular System].

MicroRNA (miRNA) miR-375 acts as a multifunctional regulator of the activity of many physiological and pathological cellular processes by interacting with a large number of target genes. MiR-375 is involved in the regulation of the differentiation and functioning of cells of the nervous and immune systems, bone and adipose tissue, and even the life cycle of a number of viruses. Changes in miR-375 expression have been found in carcinogenesis, inflammation, and autoimmune and cardiovascular diseases.

Circulating miR-499a-5p Is a Potential Biomarker of -Associated Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disease with significant genetic and phenotypic heterogeneity. To search for novel biomarkers, which could increase the accuracy of HCM diagnosis and improve understanding of its phenotype formation, we analyzed the levels of circulating miRNAs—stable non-coding RNAs involved in post-transcriptional gene regulation. Performed high throughput sequencing of miRNAs in plasma of HCM patients and controls pinpointed miR-499a-5p as one of 35 miRNAs dysregulated in HCM.

Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients.

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, which develops in genetically predisposed individuals upon exposure to environmental influences. Environmental triggers of MS, such as viral infections or smoking, were demonstrated to affect DNA methylation, and thus to involve this important epigenetic mechanism in the development of pathological process. To identify MS-associated DNA methylation hallmarks, we performed genome-wide DNA methylation profiling of two cell populations (CD4+ T-lymphocytes and CD14+ monocytes), collected from the same treatment-naive relapsing-remitting MS patients and healthy subjects, using Illumina 450 K methylation arrays.

Global transcriptome profiling in peripheral blood mononuclear cells identifies dysregulation of immune processes in individuals with radiologically isolated syndrome.

The presence of brain/spinal white matter lesions typical for multiple sclerosis (MS) in asymptomatic individuals is known as 'radiologically isolated syndrome' (RIS). Taking into account that RIS patients are at high risk of MS development, the understanding of mechanisms underlying its pathogenesis is of great importance. In order to investigate RIS-specific transcription signature we performed high-throughput RNA-sequencing in peripheral blood mononuclear cells (PBMCs) of 8 RIS patients and 8 age- and sex-matched healthy controls.

MiRNA-Regulated Pathways for Hypertrophic Cardiomyopathy: Network-Based Approach to Insight into Pathogenesis.

Hypertrophic cardiomyopathy (HCM) is the most common hereditary heart disease. The wide spread of high-throughput sequencing casts doubt on its monogenic nature, suggesting the presence of mechanisms of HCM development independent from mutations in sarcomeric genes. From this point of view, HCM may arise from the interactions of several HCM-associated genes, and from disturbance of regulation of their expression.

[Risk of Multiple Sclerosis: Analysis of Interactions Between Variants of Nuclear and Mitochondrial Genomes].

There is increasing evidence that the interaction of the mitochondrial and nuclear genomes substantially affects the risk of neurodegenerative diseases. The role of mitonuclear interactions in the development of multiple sclerosis, a severe chronic neurodegenerative disease of a polygenic nature, is poorly understood. In this work, we analyzed the association of multiple sclerosis with two-component mitonuclear combinations that include each of seven polymorphic variants of the nuclear genome localized in the region of the UCP2, and KIF1B genes and in the PVT1 locus (MYC, PVT1, and MIR1208 genes) and each often polymorphisms of the mitochondrial genome, as well as individual genetic variants that make up these combinations.

Imprinted Genes and Multiple Sclerosis: What Do We Know?

Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system that arises from interplay between non-genetic and genetic risk factors. The epigenetics functions as a link between these factors, affecting gene expression in response to external influence, and therefore should be extensively studied to improve the knowledge of MS molecular mechanisms. Among others, the epigenetic mechanisms underlie the establishment of parent-of-origin effects that appear as phenotypic differences depending on whether the allele was inherited from the mother or father.

From miRNA Target Gene Network to miRNA Function: miR-375 Might Regulate Apoptosis and Actin Dynamics in the Heart Muscle via Rho-GTPases-Dependent Pathways.

MicroRNAs (miRNAs) are short, single-stranded, non-coding ribonucleic acid (RNA) molecules, which are involved in the regulation of main biological processes, such as apoptosis or cell proliferation and differentiation, through sequence-specific interaction with target mRNAs. In this study, we propose a workflow for predicting miRNAs function by analyzing the structure of the network of their target genes. This workflow was applied to study the functional role of miR-375 in the heart muscle (myocardium), since this miRNA was previously shown to be associated with heart diseases, and data on its function in the myocardium are mostly unclear.

[Hypertrophic Cardiomyopathy as an Oligogenic Disease: Transcriptomic Arguments].

Hypertrophic cardiomyopathy (HCM) is the most common genetically determined heart pathology and is often accompanied by fatal complications. Today, the traditional view of the monogenic origin of HCM is being replaced by the idea of it as an oligogenic disease, the clinical phenotype of which is determined not only by mutations in the genes encoding sarcomere proteins in cardiomyocytes, but also by the contribution of other genes (other sarcomeric genes, non-sarcomeric protein-coding modifier genes, and regulatory non-coding RNA genes). Transcriptome analysis is an informative approach for elucidating the nature of HCM, which allows one to evaluate the expression of all genes, evaluate the effect of mutations in a gene on its transcript level, and reveal the mechanisms involved in the regulation of gene expression.

Mitonuclear interactions influence multiple sclerosis risk.

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by the autoimmune inflammation, demyelination, and neurodegeneration. This complex disease develops in genetically predisposed individuals under adverse environmental factors. To date, a large number of MS-associated polymorphic loci of the nuclear genome have been identified; however, their total variability can explain only about 48% of the observed inheritance of MS.

[Full - transcriptome analysis of miRNA expression in mononuclear cells in patients with acute decompensation of chronic heart failure of various etiologies].

Unlabelled: It is known that micro RNAs are an important regulatory element in the pathogenesis of many diseases, including cardiovascular diseases. Different levels of expression of these molecules in various pathologies makes miRNA a potential diagnostic and prognostic biomarker.

Aim: Analysis of miRNA expression levels in mononuclear blood cells (MBC) of patients with acute decompensation f chronic heart failure (CHF) of various etiologies and evaluation of the possibility of their use as a biological marker.

Collapsing the list of myocardial infarction-related differentially expressed genes into a diagnostic signature.

Background: Myocardial infarction (MI) is one of the most severe manifestations of coronary artery disease (CAD) and the leading cause of death from non-infectious diseases worldwide. It is known that the central component of CAD pathogenesis is a chronic vascular inflammation. However, the mechanisms underlying the changes that occur in T, B and NK lymphocytes, monocytes and other immune cells during CAD and MI are still poorly understood.

Protective Allele for Multiple Sclerosis HLA-DRB1*01:01 Provides Kinetic Discrimination of Myelin and Exogenous Antigenic Peptides.

Risk of the development of multiple sclerosis (MS) is known to be increased in individuals bearing distinct class II human leukocyte antigen (HLA) variants, whereas some of them may have a protective effect. Here we analyzed distribution of a highly polymorphous HLA- locus in more than one thousand relapsing-remitting MS patients and healthy individuals of Russian ethnicity. Carriage of HLA*15 and HLA*03 alleles was associated with MS risk, whereas carriage of HLA*01 and HLA*11 was found to be protective.

[The Role of microRNA in the Development of Ischemic Heart Disease].

Coronary artery disease is the most clinically significant manifestation of atherosclerosis and the main cause of morbidity and mortality around the world. Atherogenesis is a complex process, involving various types of cells and regulatory molecules. MicroRNA molecules were discovered at the end of the 20th century, and nowadays are the important regulators of several pathophysiological processes of atherogenesis.

Loading Rate of Exogenous and Autoantigenic Determinants on Major Histocompatibility Complex Class II Mediates Resistance to Multiple Sclerosis.

Genetic analysis of thousands of patients with multiple sclerosis (MS) and healthy Russian donors showed that the carriage of groups of HLA-DRB1*15 and HLA-DRB1*03 alleles is associated with the risk of MS, whereas the carriage of groups of HLA-DRB1*01 and HLA-DRB1*11 alleles is protective. Recombinant HLA-DRB1*01:01 with a high affinity can recognize the fragments of myelin basic protein (MBP), one of the autoantigens in MS. However, the comparison of the kinetic parameters of the load of MBP and viral HA peptides on HLA-DRB1*01:01, which is catalyzed by HLA-DM, showed a significantly lower rate of exchange of CLIP for MBP peptides.

[Variability of the MIR196A2 Gene as a Risk Factor in Primary-Progressive Multiple Sclerosis Development].

Multiple sclerosis is a chronic disease of the central nervous system, combining in its pathogenesis both autoimmune and neurodegenerative components, and is characterized by a highly heterogeneous clinical phenotype. Genetic susceptibility to the development of the most common relapsing-remitting course of the disease is extensively studied, while the genetic architecture of the aggressive primary progressive course of multiple sclerosis remains poorly understood. We analyzed the association of polymorphic variants in miRNA genes MIR146A, MIR196A2, and MIR499A with the risk of primary progressive multiple sclerosis one by one and in biallelic combinations with variants of immune-related genes; the analysis was performed in comparison with healthy individuals and with relapsing-remitting multiple sclerosis patients.