Publications by authors named "Marina V Klimushina"

6 Publications

  • Page 1 of 1

Associations of endothelial biomarkers, nitric oxide metabolites and endothelin, with blood pressure and coronary lesions depend on cardiovascular risk and sex to mark endothelial dysfunction on the SCORE scale.

Horm Mol Biol Clin Investig 2020 Nov 6;41(4). Epub 2020 Nov 6.

Department of Clinical Pharmacology, Sechenov First Moscow State Medical University, Moscow, Russia.

Objectives: Endothelial dysfunction contributes to the onset and progression of cardiovascular diseases. However, direct associations of vasoactive mediators with cardiovascular risk are poorly understood.

Methods: We have determined associations of circulating levels of stable metabolites of nitric oxide, nitrate and nitrite (NOx), endothelin-1, and the endothelin-1/NOx ratio with blood pressure in 177 asymptomatic subjects without signs of coronary atherosclerosis; associations with blood pressure and with presence of coronary lesions were also evaluated in 457 patients suspected to have coronary heart disease with or without coronary lesions confirmed by coronary angiography. All participants were on a low nitrate diet 24 h prior to blood sampling.

Results: In men, NOx levels were inversely correlated with blood pressure similar to women with low (0-4%) European Systematic Coronary Risk Estimation (SCORE). However, the correlation was not significant in women with high SCORE (5-8%). High systolic blood pressure over 140 mm Hg was negatively associated with NOx levels in asymptomatic men (p=0.05) but not in women. This association is disrupted in male and female patients with coronary atherosclerosis. In male patients, NOx (p=0.05), endothelin (p=0.01), and the endothelin/NOx ratio (p=0.04) were associated with presence of coronary lesions.

Conclusions: Thus, elevated cardiovascular risk according to SCORE over 4% in asymptomatic women, but not in men, is associated with a shift in markers of endothelial dysfunction. Presence of coronary lesions in patients is associated with significant changes in circulating levels of markers of endothelial dysfunction in men but not in women.
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November 2020

A Data-Driven Approach to Carrier Screening for Common Recessive Diseases.

J Pers Med 2020 Sep 22;10(3). Epub 2020 Sep 22.

Federal State Institution «National Medical Research Center for Therapy and Preventive Medicine» of the Ministry of Healthcare of the Russian Federation, Petroverigsky per., 10, bld. 3, 101000 Moscow, Russia.

Genetic screening is an advanced tool for reducing recessive disease burden. Nowadays, it is still unclear as to the number of genes or their variants that are necessary for effective screening. This paper describes the development of a carrier screening custom panel for cystic fibrosis, phenylketonuria, alpha-1 antitrypsin deficiency, and sensorineural hearing loss consisting of 116 variants in the , , and genes. The approach is based on the cheapest and fastest method, on using a small number of genes, and on the estimation of the effectiveness of carriers' detection. The custom panel was tested on a population-based cohort that included 1244 participants. Genotypes were determined by the TaqMan OpenArray Genotyping platform on the QuantStudio 12K Flex Real-Time PCR System. The frequency of heterozygotes in the Russian population was 16.87% or 1:6 (CI95%: 14.76-19.00% by Clopper-Pearson exact method): in -2.81% (1:36), -2.33% (1:43), -4.90% (1:20), and -6.83% (1:15). The data on allele frequencies were obtained for the first time on a Russian population. The panel allows us to identify the vast majority of carriers of recessive diseases in the population. It is an effective approach to carrier screening for common recessive diseases.
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September 2020

Levels of nitric oxide metabolites, adiponectin and endothelin are associated with SNPs of the adiponectin and endothelin genes.

Biomed Rep 2019 Oct 4;11(4):154-164. Epub 2019 Sep 4.

National Medical Research Center for Preventive Medicine, Ministry of Healthcare of The Russian Federation, Moscow 101990, Russia.

Adiponectin, endothelin and nitric oxide (NO) are major regulators of vascular function. An imbalance of vasoactive factors contributes to the onset and progression of atherosclerosis. Various single nucleotide polymorphisms (SNPs) are considered to be risk factors for coronary heart disease. However, the molecular mechanisms of their associations with the components of endothelial dysfunction are poorly understood. In the present study, rs17366743, rs17300539, rs266729, rs182052 and rs2241766 SNPs of the adiponectin () gene and rs2070699, rs1800542 and rs1800543 SNPs of the endothelin-1 () gene were genotyped in 477 patients with coronary heart disease who were subjected to coronary angiography, in order to determine the presence or absence of coronary atherosclerosis. The serum levels of adiponectin, endothelin and stable metabolites of NO, (nitrate and nitrite NOx), were assayed and their associations with the SNP genotypes and coronary lesions were calculated. The results indicated that rs17366743 of the gene and rs2070699 and rs1800543 of the gene were associated with the levels of NOx in women, which in turn was associated with cardiovascular mortality. In men, rs182052 and rs266729 of the gene were associated with adiponectin levels, whereas rs17366743 of the gene was associated with endothelin levels. Additionally, these SNPs were indirectly associated with the prevalence of coronary lesions in men. Therefore, the tested SNPs can be considered potential risk factors that lead to imbalance of vasoactive mediators in a gender-specific manner and contribute to the development of clinical manifestations of atherosclerosis.
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October 2019

Increase in perfused boundary region of endothelial glycocalyx is associated with higher prevalence of ischemic heart disease and lesions of microcirculation and vascular wall.

Microcirculation 2018 05;25(4):e12454

National Research Center for Preventive Medicine, Ministry of Healthcare of Russian Federation, Moscow, Russia.

Objective: PBR characterizes penetration of red blood cells inside glycocalyx and its thickness can have profound impact on microcirculation and other vascular parameters. The goal of our study was to reliably quantify PBR and assess its potential use as a new marker of cardiovascular pathology.

Methods: The study included 208 patients (123 men and 85 women from 40 to 65 years of age) with various grades of cardiovascular SCORE risk index and IHD. PBR was quantified by sidestream dark field capillaroscopy with green light excitation. Cutaneous microcirculation was evaluated with laser Doppler fluorometry.

Results: Elevated PBR values over 2 mm were associated with morphological and functional lesions of arterial wall and microcirculation and lowered levels of ApoA1 lipoprotein. Moreover, elevated PBR values were associated with 2.07-fold increase in prevalence of cerebral atherosclerosis (P = .015) and 2.42-fold increase in prevalence of IHD (P = .024). Increase in PBR was associated with elevated systolic blood pressure.

Conclusions: Thus, PBR can be considered a new highly reproducible and promising marker candidate for non-invasive diagnostics of IHD and cerebral atherosclerosis suggesting important role of microcirculation in development and progression of cardiovascular diseases.
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May 2018

Variation in Copy Number of Ty3/Gypsy Centromeric Retrotransposons in the Genomes of Thinopyrum intermedium and Its Diploid Progenitors.

PLoS One 2016 27;11(4):e0154241. Epub 2016 Apr 27.

Centre for Molecular Biotechnology, Russian State Agrarian University-Moscow Timiryazev Agricultural Academy, Timiryazevskaya St. 49, 127550, Moscow, Russia.

Speciation and allopolyploidization in cereals may be accompanied by dramatic changes in abundance of centromeric repeated transposable elements. Here we demonstrate that the reverse transcriptase part of Ty3/gypsy centromeric retrotransposon (RT-CR) is highly conservative in the segmental hexaploid Thinopyrum intermedium (JrJvsSt) and its possible diploid progenitors Th. bessarabicum (Jb), Pseudoroegneria spicata (St) and Dasypyrum villosum (V) but the abundance of the repeats varied to a large extent. Fluorescence in situ hybridization (FISH) showed hybridization signals in centromeric region of all chromosomes in the studied species, although the intensity of the signals drastically differed. In Th. intermedium, the strongest signal of RT-CR probe was detected on the chromosomes of Jv, intermediate on Jr and faint on Js and St subgenome suggesting different abundance of RT-CR on the individual chromosomes rather than the sequence specificity of RT-CRs of the subgenomes. RT-CR quantification using real-time PCR revealed that its content per genome in Th. bessarabicum is ~ 2 times and P. spicata is ~ 1,5 times higher than in genome of D. villosum. The possible burst of Ty3/gypsy centromeric retrotransposon in Th. intermedium during allopolyploidization and its role in proper mitotic and meiotic chromosome behavior in a nascent allopolyploid is discussed.
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March 2017

Serum nitrate and nitrite are associated with the prevalence of various chronic diseases except cancer.

Int Angiol 2017 Apr 19;36(2):160-166. Epub 2016 Feb 19.

National Research Center for Preventive Medicine of the Ministry of Healthcare, Moscow, Russia.

Background: Nitric oxide and its metabolites, nitrate and nitrite, are important regulators linked to various diseases. We studied the association of fasting serum concentrations of nitrate and nitrite, combined as NOx, without special diet, with the prevalence of various chronic diseases.

Methods: Fasting concentrations of NOx were assayed in a cohort of 1087 patients recruited to Stress Aging and Health in Russia study that represents male and female population in Moscow, Russia, over 55 years of age. Chronic diseases were recorded based on anamnesis and additional assays were run to characterize immune status and lipid and carbohydrate metabolism. Odds ratios were calculated to associate NOx concentrations with prevalence of chronic diseases in pooled deciles below or above borderline.

Results: NOx over 44.7 µM were associated with increased prevalence of various chronic diseases such as diabetes type II, hyperthyroidism, coronary heart disease, gout and thrombosis/stroke. NOx 65.3 µM and above were associated with lowered prevalence of osteoporosis. NOx levels of 74.6 µM and above were associated with significantly higher number of patients who abstain from consumption of alcoholic beverages. NOx were not associated with cancer.

Conclusions: Thus, fasting concentrations of NOx in serum can be an important diagnostic parameter characteristic for specific chronic diseases.
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April 2017