[Clinical protocol: audiological assessment of infants in Russian Federation. Part II]. / Protokol audiologicheskogo obsledovaniya detei pervogo goda zhizni v Rossiiskoi Federatsii. Chast' II.

This is the second part of the previously published clinical protocol of audiological assessment in infants. The goal of the protocol is unification approaches to audiological diagnosis of the infants. The following sections were included in the second part of the protocol: behavioral testing in infants, testing sequence, duration of the examination and necessity in follow-up, hearing assessment in special cases (premature children, children with congenital infections, after meningitis, with external ear abnormalities, single-sided deafness, with hydrocephalus and shunts, with auditory neuropathy spectrum disorder, with mild hearing loss and otitis media with effusion), medical report.

[Clinical protocol: audiological assessment of infants in Russian Federation. Part I]. / Protokol audiologicheskogo obsledovaniya detei pervogo goda zhizni v Rossiiskoi Federatsii. Chast' I.

The clinical protocol of audiological assessment in infants was prepared by the workgroup of Russian pediatric audiologists from different regions. The goal of the protocol is unification approaches to audiological diagnosis of the infants. The protocol has been developed according the evidence based medicine principles, by reviewing current scientific publications on the topic and taking into account the order of providing medical services and other clinical practice guidelines. When direct evidence was not available, both indirect evidence and consensus practice were considered in making recommendations. This guideline is not intended to serve as a standard to dictate precisely how the child should be diagnosed. This guideline is meant to provide the evidence base from which the clinician can make individualized decisions for each patient. The first part of the protocol covers following sections: equipment, staff requirements, timing of the diagnostics, case history and risk factors, preparing the child for the appointment, sedation and general anesthesia, otoscopy, tympanometry and acoustic reflex, otoacoustic emissions, skin preparing, electrode montage, choosing the stimulators, auditory brainstem responses on broadband and narrow-band stimuli, on bone conducted stimuli, auditory steady-state responses, masking, combined correction factors.

[Prospects for cochlear implantation in patients with auditory nerve dysplasia]. / Perspektivy kokhlearnoi implantatsii u patsientov s displaziei slukhovogo nerva.

Auditory nerve dysplasia (AND) can encompass various conditions of the auditory nerve (AN), ranging from true aplasia to hypoplasia. The purpose of this review is to discuss the prospect of cochlear implantation (CI) and subsequent auditory speech rehabilitation for AN abnormality. Studies of different authors when working with this category of children, possible results and methods of diagnostics of the AN condition are presented.

[Epidemiological characteristics of the pediatric population of cochlear implant users in St. Petersburg]. / Epidemiologicheskaya kharakteristika detskoi populyatsii pol'zovatelei kokhlearnykh implantatov Sankt-Peterburga.

An epidemiological analysis of the pediatric population of cochlear implant (CI) users in St. Petersburg, the second largest metropolis of Russian Federation, was carried out. CI users are 14% of the total number of hearing impaired children, and 26% of children with hearing devices. Only 43% of children who are candidates for cochlear implantation in according to audiological criteria use CI. Since 2012, unilateral cochlear implantation has been carried out for all children in need - their annual number ranges from 25 to 45. Bilateral implantation, mostly sequential with an interval of 1-3 years, was performed in 21% of children The average age at the time of the surgery was 3 years, more than 50% of children were implanted between 1 and 3 years. In recent years, the number of children implanted before 2 years has increased, as well as the number of children implanted at school age. 27% of children with CI continue wearing a hearing aid on the opposite ear. 23% of implanted children have additional disabilities. It has been established that the proportion of children attending mainstream educational institutions is significantly higher among children with CI, compared with children using hearing aids. Some directions have been developed to improve care for CI children and to increase the effectiveness of cochlear implantation as a medical-technical-pedagogical technology for hearing restoration in a regional centre for hearing impaired children.

[Identification of Functionally Significant Polymorphic Variants in miRNA Genes in Carotid Atherosclerosis].

miRNAs are vital molecules of gene expression. They are involved in the pathogenesis of various common diseases, including atherosclerosis, its risk factors, and its complications. A detailed characterization of the spectrum of functionally significant polymorphisms of miRNA genes in patients with advanced carotid atherosclerosis is an important research task. We analyzed miRNA expression and exome sequencing data of carotid atherosclerotic plaques of male patients (n = 8, 66-71 years of age, 67-90% degree of carotid artery stenosis). For further study and analysis of the association between the rs2910164 polymorphism of the MIR146A gene and advanced carotid atherosclerosis, we recruited 112 patients and 72 relatively healthy Slavic residents of Western Siberia. A total of 321 and 97 single nucleotide variants (SNVs) were detected in the nucleotide sequences of pre- and mature miRNAs in carotid atherosclerotic plaques. These variants were located in 206 and 76 miRNA genes, respectively. Integration of the data of exome sequencing and miRNA expression revealed 24 SNVs of 18 miRNA genes that were processed to mature form in carotid atherosclerotic plaques. SNVs with the greatest potential functional significance for miRNA expression predicted in silico were rs2910164:C>G (MIR146A), rs2682818:A>C (MIR618), rs3746444:A>G (MIR499A), rs776722712:C>T (MIR186), rs199822597:G>A (MIR363). The expression of miR-618 was lower in carotid atherosclerotic plaques of patients with the AC rs2682818 genotype of the MIR618 gene compared with the CC genotype (log2FC = 4.8; p = 0.012). We also found an association of rs2910164:C (MIR146A) with the risk of advanced carotid atherosclerosis (OR = 2.35; 95% CI: 1.43-3.85; p = 0.001). Integrative analysis of polymorphisms in miRNA genes and miRNA expression is informative for identifying functionally significant polymorphisms in miRNA genes. The rs2682818:A>C (MIR618) is a candidate for regulating miRNA expression in carotid atherosclerotic plaques. The rs2910164:C (MIR146A) is associated with the risk of advanced carotid atherosclerosis.

[Peculiarities of CI processor fitting in children with auditory neuropathy spectrum disorders]. / Osobennosti nastroiki protsessora kokhlearnogo implantata u detei so slukhovoi (auditornoi) neiropatiei.

The peculiarities of cochlear implant (CI) processor fitting in children with auditory neuropathy spectrum disorders (ANSD) were investigated. At the 1-st fitting of the CI processor a standard protocol of parameters was used in all patients, including patients with cochlear nerve hypoplasia. After the initial fitting session, the behavioral tonal thresholds with CI in 55% of patients were 30-35 dB, in 32.% of patients - 40-50 dB. After 3-6 months, 65% of children with ANSD showed significant progress in auditory-speech development, which made it possible to use the standard protocol of tuning parameters for them with the most comfortable and threshold levels of electrical stimulation adjusted according to the child's reactions. The best dynamics was observed in 2 children with presynaptic ANSD with a confirmed DFNB9 (OTOF) gene mutation. In 35% of children, there was no progress in distinguishing speech signals and instability of reactions to sounds persisted after 6 months using of CI and speech therapy training, despite the low tonal thresholds of hearing. In these children the coding strategy was changed, the stimulation frequency was reduced, and the pulse width was increased. This helped to improve the discrimination of sounds with CI and progress in the child's speech development. The results demonstrate that children with ANSD require more frequent correction of CI processor settings: 1st year - every 3 months, then at least 2 times a year until the optimal coding strategy and settings are achieved. To predict the effectiveness of CI and determine the optimal tactics for setting up the CI processor in patients with ANSD, the preoperative examination should include MRI of the cerebellopontine angle to detect anomalies of the cochlear nerve and genetic examination to identify mutations that cause hearing impairment in patients with ANSD.

[Results of the audit of the first stage newborn hearing screening in St. Petersburg]. / Rezul'taty audita pervogo etapa audiologicheskogo skrininga novorozhdennykh v Sankt-Peterburge.

OBJECTIVE: Analysis of the first stage of universal newborn hearing screening in St. Petersburg and increasing its effectiveness. RESULTS: In result of the audit, it was found that screening performs in all maternity wards, children's hospitals and at the majority of pediatric clinics. Meanwhile only 14% of institutions meet criteria of good practice in providing screening. In other clinics improving the procedure of screening is needed: equipment update and calibration, correction of the method and conditions of examination, results documenting, etc. The set of activities for increasing the effectiveness of newborn hearing screening is proposed. The work which carried out with institutions during and after audit allowed to reach 100% involving clinics in screening system in 6 months. Due to information support of institutions coverage of newborns by the first stage of screening increased on 8.5% (matched to target) and the number of referred children who come to the second stage of screening increased on 18%. Results suggest that the audit of the first stage of newborn hearing screening by the district pediatric audiological centers is an effective tool for finding problems in the screening system and its solving.

Changes in DNA methylation profile in liver tissue during progression of HCV-induced fibrosis to hepatocellular carcinoma.

In this study we compared methylation levels of 27,578 CpG sites between paired samples of the tumor and surrounding liver tissues with various degrees of damage (fibrosis, cirrhosis) in HCV-induced hepatocellular carcinoma (HCC) patients, as well as between tumor and normal tissue in non-viral HCC patients, using GSE73003 and GSE37988 data from GEODataSets (https://www.ncbi.nlm.nih.gov/). A significantly lower number of differentially methylated sites (DMS) were found between HCC of non-viral etiology and normal liver tissue, as well as between HCC and fibrosis (32 and 40), than between HCC and cirrhosis (2450 and 2304, respectively, according to GSE73003 and GSE37988 datasets). As the pathological changes in the tissue surrounding the tumor progress, the ratio of hyper-/hypomethylated DMSs in the tumor decreases. Thus, in tumor tissues compared with normal/fibrosis/cirrhosis of the liver, 75/62.5/47.7 % (GSE73003) and 16 % (GSE37988) of CpG sites are hypermethylated, respectively. Persistent hypermethylation of the ZNF154 and ZNF540 genes, as well as CCL20 hypomethylation, were registered in tumor tissue in relation to both liver fibrosis and liver cirrhosis. Protein products of the EDG4, CCL20, GPR109A, and GRM8 genes, whose CpG sites are characterized by changes in DNA methylation level in tumor tissue in the setting of cirrhosis and fibrosis, belong to "Signaling by G-protein-coupled receptors (GPCRs)" category. However, changes in the methylation level of the "driver" genes for oncopathology (АРС, CDKN2B, GSTP1, ELF4, TERT, WT1) are registered in tumor tissue in the setting of liver cirrhosis but not fibrosis. Among the genes hypermethylated in tumor tissue in the setting of liver cirrhosis, the most represented biological pathways are developmental processes, cell-cell signaling, transcription regulation, Wnt-protein binding. Genes hypomethylated in liver tumor tissue in the setting of liver cirrhosis are related to olfactory signal transduction, neuroactive ligand-receptor interaction, keratinization, immune response, inhibition of serine proteases, and zinc metabolism. The genes hypermethylated in the tumor are located at the 7p15.2 locus in the HOXA cluster region, and the hypomethylated CpG sites occupy extended regions of the genome in the gene clusters of olfactory receptors (11p15.4), keratin and keratin-associated proteins (12q13.13, 17q21.2, and 21q22.11), epidermal differentiation complex (1q21.3), and immune system function loci 9p21.3 (IFNA, IFNB1, IFNW1 cluster) and 19q13.41-19q13.42 (KLK, SIGLEC, LILR, KIR clusters). Among the genes of fibrogenesis or DNA repair, cg14143055 (ADAMDEC1) is located in the binding region of the HOX gene family transcription factors (TFs), while cg05921699 (CD79A), cg06196379 (TREM1) and cg10990993 (MLH1) are located in the binding region of the ZNF protein family transcription factor (TF). Thus, the DNA methylation profile in the liver in HCV-induced HCC is unique and differs depending on the degree of surrounding tissue lesion - liver fibrosis or liver cirrhosis.

[Telerehabilitation of hearing-impaired children during COVID-19 pandemic]. / Distantsionnaya reabilitatsiya detei s tugoukhost'yu v period pandemii COVID-19 v usloviyakh surdologicheskogo tsentra.

OBJECTIVE: To evaluate advantages and effectiveness of remote rehabilitation services for hearing-impaired children at Center of Pediatric Audiology during COVID-19 pandemic. MATERIAL AND METHODS: 181 children with different types and degrees of permanent hearing loss, their parents and 10 hearing care professionals (audiologists, speech-language therapists) were included in the study. 2115 rehabilitation services were provided during 3 months: video- and text consultations, video lessons with child, sending homework to parents, etc. RESULTS: The results of questionnaires showed that, on specialists' and parents' opinion, remote rehabilitation care is effective tool for hearing impaired children during emergency situations. TeleCare allowed to improve parents' abilities to manage with children by themselves, their understanding goals and methods of rehabilitation, improving child's hearing and speech skills. 95% of parents were satisfied by remote rehabilitation. Advantages and problems of remote hearing rehabilitation were analyzed from the sides of professionals and parents. The most challenging activities for professionals during TeleCare were: evaluation of HA/CI effectiveness, diagnosis and developing of hearing and speech. CONCLUSIONS: The experience of remote hearing rehabilitation in emergency situation allows to conclude that this type of care could be useful in clinical practice after pandemic for parents consulting and for children with motor problems.

[miRNA Regulome in Different Atherosclerosis Phenotypes].

Dysregulation of microRNA (miRNA) expression is associated with a susceptibility to many diseases, including atherosclerotic lesions of the coronary and carotid arteries and the development of clinical complications such as coronary heart disease, myocardial infarction, chronic cerebral ischemia, ischemic stroke. Recently, more and more studies analyze the miRNA regulome including a network of regulatory elements for the expression of miRNAs themselves and targets under their control. The review summarizes the data from articles concerned miRNA expression and changes in DNA methylation in the miRNA genes in human atherosclerotic arteries, as well as with the analysis of the association between single nucleotide polymorphisms and copy number variations in the miRNA genes with clinical complications of atherosclerosis.

[Epidemiological study of hearing impairments in children: prevalence, structure, amplification, and social factors]. / Epidemiologiya narushenii slukha u detei: rasprostranennost', struktura, aspekty slukhoprotezirovaniya i sotsial'nye faktory.

For the first time, a detailed epidemiological study of hearing impairments (HI) in the children's population of St. Petersburg (n=3098) was conducted. The data on the incidence of HI in children, the distribution of children depending on the degree of hearing loss, HI type, the presence of additional disorders, risk factors for hearing loss were obtained. Only 19% of children with HI were diagnosed in accordance with modern requirements of early care - at the age of 3 months. In children who underwent universal newborn hearing screening the average age of diagnosis was significantly lower than in children who were not screened. Only 54% of HI children use hearing aids (HA) or cochlear implants. Among the children who do not use HA, the main number is children with mild and moderate hearing loss, unilateral hearing loss and otitis media with effusion. A significant part of them should be considered as candidates for amplification according to current recommendations. The average interval between diagnosis and amplification was 15.7 months. Only 5% of children from the entire population of children with HI received early intervention in accordance with the modern time standard: 1 month (detection) - 3 months (diagnosis) - 6 months (amplification). The problems of organizing an effective care for HI children and the directions of its development are discussed: improving newborn hearing screening; introduction the system of informing the citizens and doctors of related specialties (pediatricians, neurologists) in the field of prevention, diagnosis and rehabilitation of HI in children; expansion of genetic testing of children; reducing time of waiting and improving the quality of HA provided to handicapped children.

The benefits of underwater vibrostimulation in the rehabilitation of children with impaired hearing.

INTRODUCTION: Early intervention is crucial for the optimal speech and language development of children with impaired hearing. Underwater vibrostimulation could help develop behavioural reactions to low-frequency stimuli immediately after diagnosis and facilitate aural rehabilitation after hearing aid (HA) or cochlear implant (CI) activation. GOALS: To determine the limits of underwater vibrotactile stimuli perception and to measure the effect of vibrostimulation training on the aural rehabilitation of young children. METHODS: Two adults and three children with congenital hearing loss participated in the first part of the study. Pure tones between 100 and 4000 Hz and natural broadband sounds were delivered under water while the participants were sitting in a pool. The lower thresholds of perception and the maximum comfortable levels were measured and the subjective sensations were recorded. In the second part of the study, 15 children <3 years old were presented with the same stimuli until they developed stable conditioned reactions to the stimuli. The time until the development of "hearing behaviour" and the number of fitting sessions after HA or CI activation were compared between the vibrostimulation group and a control group who did not receive such training. RESULTS: In the first part of the study, participants were most sensitive to 100-400 Hz stimuli, while the stimuli >1000 Hz did not evoke any sensations. The vibrations were felt across all body parts and produced hearing-like sensations in the ear. In the second part of the study, children in the vibrostimulation group required fewer fitting sessions and developed "hearing behaviour" sooner than the control group. CONCLUSIONS: Underwater vibrostimulation is a promising new method of early aural rehabilitation that could be recommended for implementation in paediatric audiology centres.

[Psychoacoustic tests for perceptual assessment of processor fitting in patients with cochlear implants]. / Ispol'zovanie psikhoakusticheskikh testov dlya pertseptivnoi otsenki nastroiki protsessora kokhlearnogo implanta u glukhikh patsientov.

THE AIM OF THE STUDY: Was to study the possibility of using a battery of psychoacoustic tests to assess the tuning of the cochlear implant processor (CI) in deaf patients. METHODOLOGY: The study involved 60 prellingually deaf patients aged 10 to 23 years with oral speech skills. To assess the quality of the CI processor tuning, in addition to traditional methods, a special battery of psychoacoustic tests was used. The first block of tests assessed the perception of the basic characteristics of sound signals (duration, temporal structure, spectrum, timbre) and was used to assess the initial setting. The second block of tests, intended for patients with experience using CI, included tasks to distinguish acoustically similar and dynamically changing signals, etc. RESULTS: At the end of the initial CI setup session, patients with short signal perception problems were identified. Adjusting the frequency of electrical stimulation in patients has increased their ability to distinguish between sounds. During the second tuning session of the CI processor, 6 months later, a group of patients with difficulties in perceiving acoustic information in the low-frequency range was identified - distinguishing melodic intervals, changing the pitch of sounds, highlighting the voice of the target speaker. The «problem¼ patients underwent additional correction of the CI processor setting and the corresponding auditory training, which improved the test performance and subjective perception of sounds. CONCLUSION: The use of psychoacoustic tests expands the possibilities of fine tuning the CI processor, taking into account the individual characteristics of the patient's auditory perception at different stages of CI use, especially in «problem¼ patients.

[Comparative Analysis of MPTP Neurotoxicity in Mice with a Constitutive Knockout of the α-Synuclein Gene].

Aggregated forms of α-synuclein are core components of pathohistological inclusions known as Lewy bodies in substantia nigra (SN) neurons of patients with Parkinson's disease (PD). The role of α-synuclein in selective loss of SN dopaminergic neurons (DNs) in PD is studied in mice knocked out in the α-synuclein gene. The new mouse strain delta flox KO with a constitutive knockout of the α-synuclein gene models the end point of in vivo deletion of the α-synuclein gene in mice with a conditional knockout and has no foreign sequence in the modified genomic locus, thus differing from all other α-synuclein knockout mouse strains. The effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is used to model PD, was compared between delta flox KO mice and mice of the well-known α-synuclein knockout strain AbKO. Subchronic MPTP administration, which models early PD, was found to reduce the dopamine content and to change the ratio of dopamine metabolites in the striatum to the same levels in delta flox KO, АbKO, and wild-type mice. Overt locomotor defects were not observed after MPTP treatment, but gait testing in a CatWalk XT (Noldus) system revealed identical gait deviations in mice of the two strains and control wild-type mice. Based on the findings, a similar mechanism of neurotoxic damage to DNs was assumed for delta flox KO and AbKO mice.

[Complex disorders in children with sensorineural hearing loss - influence on the diagnosis of hearing pathology and hearing aid]. / Kompleksnye narusheniya u detei s sensonevral'noi tugoukhost'yu ­ vliyanie na diagnostiku patologii slukha i slukhoprotezirovanie.

The presence of additional disabilities (AD) in children with sensorineural hearing loss (SNHL) and influence of AD on age of hearing loss diagnosis and amplification were investigated. It was shown that 41% children with SNHL have different AD - pathology of the central neural system (including mental retardation, autism spectrum disorders, attention deficits), vision, motor and articulation impairments, cardiovascular, respiratory, urinary, digestive, endocrine diseases etc. 59% children among them have 2-3 AD. The most often combination of AD was pathology of central neural and motor systems. The genetic factor was revealed rarely in the group of children with AD than in children with SNHL only. The diagnosis of hearing loss before age 4 months was rarely in the group of children with AD. Possibly it is because of the most of such children got treatment in neonatal intensive care unit and didn't have access to universal newborn hearing screening. Moreover, SNHL might develop later as the outcome of their AD or their treatment. Suggestion about more late amplification in children with SNHL was confirmed. The cause might be wary relation of audiologists to amplification of children with AD and difficulties of this process.

[Organizing the medical care for the COVID-19 patients in non-infectious Moscow hospital: reassignment experience].

AIM: To present the results of work of National Medical Research Center of Treatment and Rehabilitation, reassigned for COVID-19 patients treatment during pandemic. Run-up methodology, procedures and working process organization are detailed. MATERIALS AND METHODS: 354 COVID-19 patients were treated from 13.04.2020 to 10.06.2020 [age 59 (470) years, 56% women, body mass index 28.5 (24.932.2) kg/m2]. Patients were admitted at 8 (611) day of sickness. In-hospital stay was 16 (1420) days. RESULTS: NEWS scale at the day of admittance was 2 (14); 2 (13) in patients discharged alive and 6 (47) in died patients, p=0.0001. So prognostic accuracy of NEWS scale was confirmed as very well (area under ROC-curve = 0.819). 69 patients (19.5%) were treated at intensive care department for 7 (413) days. 13 patients died, 11 of them had COVID-19 as direct or indirect cause of death. Total in-hospital mortality was 3.67%, in-hospital mortality of COVID-19 patients 3.1%. 17 healthcare workers (HCW), contacted with COVID-19 patients were infected (2.67%). 4 HCW, who had no direct contact with patients were also infected and 7 HCW were infected before the first patient was admitted. No one of them died. CONCLUSION: Complex tasks of healthcare organization during COVID-19 pandemic can be solved quickly with acceptable quality, characterized by low levels of patients; mortality and HCW infection.

[Sequential bilateral cochlear implantation with long interval between surgeries in deaf-blind patient]. / Posledovatel'naia bilateral'naia kokhlearnaia implantatsiia s dlitel'nym intervalom mezhdu operatsiiami u slepoglukhogo patsienta.

The efficacy of sequential bilateral cochlear implantation with long interval between surgeries (18 years) was investigated in deaf-blind patient (22 years old man, lost hearing and vision after meningitis at the age 2.5 years). At the age 4 years he got cochlear implant at right ear. His speech skills completely disappeared before the implantation. Auditory-speech rehabilitation with cochlear implant was successful - patient has good auditory, language, speech, cognitive skills. At the age 22 years patient made decision to get cochlear implant at the left ear after breakdown of internal part of cochlear implant at right ear in spite of successful reoperation. After activation of new processor (all electrodes were activated) the patient got daily auditory training with cochlear implant at left ear (Concerto/Opus 2, Medel) on the base of 'auditory' method, in daily life patient uses 2 devices. After 1 month of using cochlear implant at left ear the patient recognized environmental sounds and music instruments, words and sentences in close set tests EARS battery, the score for OLSA test in quiet was 90%, but the perception in noise was complicated. The balance of parameters of fitting for 1-st and 2-nd processors and special auditory training with two cochlear implants provided the development of initial binaural interaction. Perilinqually deaf patients can achieve high effect after sequential bilateral cochlear implantation with long interval between surgeries. The necessary conditions are - preservation of electrical activity of auditory nerve, intensive structured auditory training with new 'ear', patient's motivation of using of cochlear implant at 'new' ear.

[Comparative analysis of gene expression in vascular cells of patients with advanced atherosclerosis]. / Sravnitel'nyi analiz ékspressii genov v kletkakh sosudov u bol'nykh s klinicheski vyrazhennym aterosklerozom.

In this study we performed a comparative gene expression analysis of carotid arteries in the area of atherosclerotic plaques and healthy internal mammary arteries of patients with advanced atherosclerosis by using microarray HumanHT-12 BeadChip ("Illumina"). The most down-regulated genes were APOD, FABP4, CIDEC and FOSB, and up-regulated gene was SPP1 (|FC|>64; pFDR<0.05). The majority of differentially expressed genes were down-regulated in advanced atherosclerotic plaques. Unexpectedly, genes involved in immune and inflammatory responses were down-regulated in advanced atherosclerotic plaques to compare with the healthy arteries (arachidonic acid metabolism, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, Jak-STAT signaling pathway, TNF signaling pathway). "Cellular response to metal ion" (metallothioneins) and "Extracellular matrix organization" were the most significant Gene ontology terms among the down- and up-regulated genes, respectively.

Role of microRNA in Development of Instability of Atherosclerotic Plaques.

MicroRNAs are small noncoding single-stranded RNAs that regulate gene expression. Today, we see an increasing number of studies highlighting the important role of microRNAs in the development and progression of cardiovascular diseases caused by atherosclerotic lesions of arteries. We review the available scientific data on association of the expression of these biomolecules with instability of atherosclerotic plaques in animal models and humans. We made special emphasis on miR-21, -100, -127, -133, -143/145, -221/222, and -494 because they were analyzed in more than one study. We discuss the possibility of microRNAs using in the diagnosis and therapy of atherosclerosis and its complications.

Variability of Methylation Profiles of CpG Sites in microrNA Genes in Leukocytes and Vascular Tissues of Patients with Atherosclerosis.

In this study, we for the first time described the variability of methylation levels of 71 CpG sites in microRNA genes in leukocytes and blood vessels (coronary artery atherosclerotic plaques, intact internal thoracic arteries, and great saphenous veins) in patients with atherosclerosis using the Infinium HumanMethylation27 BeadChip microarray. Most of the analyzed CpG sites were characterized by the low variability, and most of these low-variable sites were hypomethylated in all tissue samples. CpG sites in coronary artery atherosclerotic plaques and leukocytes were similar in their methylation status. The highest variability of CpG methylation levels between different tissues was found for the CpG sites of the MIR10B gene; the methylation levels of these sites in leukocytes and atherosclerotic arteries were lower than in intact blood vessels. We also found that several cardiovascular disease risk factors, as well as medications, might affect methylation levels of CpG sites in microRNAs.