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Nazarenko M.S.,Tomsk State University | Markov A.V.,Tomsk State University | Lebedev I.N.,Tomsk State University | Freidin M.B.,Research Institute of Medical Genetics | And 6 more authors.
PLoS ONE | Year: 2015

Epigenetic mechanisms of gene regulation in context of cardiovascular diseases are of considerable interest. So far, our current knowledge of the DNA methylation profiles for atherosclerosis affected and healthy human vascular tissues is still limited. Using the Illumina Infinium Human Methylation27 BeadChip, we performed a genome-wide analysis of DNA methylation in right coronary artery in the area of advanced atherosclerotic plaques, atherosclerotic-resistant internal mammary arteries, and great saphenous veins obtained from same patients with coronary heart disease. The resulting DNA methylation patterns were markedly different between all the vascular tissues. The genes hypomethylated in athero-prone arteries to compare with atherosclerotic-resistant arteries were predominately involved in regulation of inflammation and immune processes, as well as development. The great saphenous veins exhibited an increase of the DNA methylation age in comparison to the internal mammary arteries. Gene ontology analysis for genes harboring hypermethylated CpG-sites in veins revealed the enrichment for biological processes associated with the development. Four CpG-sites located within the MIR10B gene sequence and about 1 kb upstream of the HOXD4 gene were also confirmed as hypomethylated in the independent dataset of the right coronary arteries in the area of advanced atherosclerotic plaques in comparison with the other vascular tissues. The DNA methylation differences observed in vascular tissues of patients with coronary heart disease can provide new insights into the mechanisms underlying the development of pathology and explanation for the difference in graft patency after coronary artery bypass grafting surgery. © 2015 Nazarenko et al. Source


Ovcharenko E.A.,Research Institute for Complex Problems of Cardiovascular Diseases | Klyshnikov K.Y.,Research Institute for Complex Problems of Cardiovascular Diseases | Nushtaev D.V.,OOO Tesis | Savrasov G.V.,Moscow State University | Barbarash L.S.,Research Institute for Complex Problems of Cardiovascular Diseases
Biophysics (Russian Federation) | Year: 2015

The relationships between the geometric parameters of the tubular leaflet apparatus and its functional characteristics have been analyzed. The effects of the deformation of different parts of the leaflet apparatus on its functionality have been evaluated. The results of the study can be used to develop new models of the leaflet apparatus for transcatheter prosthetic heart valves or for evaluation of existing designs. © 2015, Pleiades Publishing, Inc. Source


Karetnikova V.N.,Kemerovo State Medical Academy | Evseeva M.V.,Kemerovo State Medical Academy | Zykov M.V.,Kemerovo State Medical Academy | Bykova I.S.,Research Institute for Complex Problems of Cardiovascular Diseases | And 5 more authors.
Kardiologiya | Year: 2015

Purpose. To elucidate association of renal dysfunction (RD) with unfavorable outcomes of in-hospital and long-term (t year) treatment stages of patients with ST-elevation (STE) myocardial infarction (Ml) and concomitant diabetes mellitus (DM). Materia/ and methods. We enrolled in this register study 954 patients (65% men, 35% women, mean age 63.4 [62.6-64.2) years) with STE acute coronary syndrome. Mean age of men was 60.3 (59.4-61.1), of women - 69.2 [68.1-70.4] years. DM was verified in 175 patients (18.3%) basing on history data and values of fasting and postprandial glycaemia. Glomerular filtration rate (GFR) was calculated by MDRD formula using serum creatinine level determined at admission. Results. Four groups of patients were distinguished depending on the presence of DM and RD: With DM and RD (n=82), with DM without RD (n = 93), without DM with RD (n = 269) and without DM and RD (n = 510). Presence of RD in acute period of Ml was associated with 3.3-fold increase of risk of in-hospital and annual mortality, while the presence of DM was associated with 1.6-fold increase of in-hospital mortality without significant impact on annual mortality. Conclusion. RD had a significant impact on realization of poor outcomes in STEMI patients with concomitant DM. Prognostic significance of combination of DM and RD was proved to be higher than that of isolated DM. Source


Zykov M.V.,Research Institute for Complex Problems of Cardiovascular Diseases | Makeeva O.A.,Research Institute for Complex Problems of Cardiovascular Diseases | Golubenko M.V.,Research Institute for Complex Problems of Cardiovascular Diseases | Kashtalap V.V.,Kemerovo State Medical Academy | And 6 more authors.
Kardiologiya | Year: 2016

Aim: to study associations of polymorphic genetic variants of inflammatory response, endothelial function, lipid metabolism, and blood coagulation with impaired renal function in patients with ST elevation myocardial infarction (STEMI). Material and methods. We enrolled in the study 171 patients admitted to the Kemerovo Cardiology Dispensary within 24 hours after onset of STEMI. All patients underwent genotype identification of 25 polymorphic variants of 18 major candidate genes for cardiovascular disease. Genotyping was performed with DNA chip SINKAR-1 (Institute of Medical Genetics and LLC «Genomic Diagnosis»). Glomerular filtration rate (GFR) was estimated using serum creatinine level measured at admission. Results: Comparison of allelic and genotype frequencies of the studied polymorphisms revealed that angiotensin-converting enzyme (ACE) gene rs4291 was associated with decreased GFR: odds ratio (OR) for carriers of rare TT genotype was 2.31 [1.01-5.25], p=0.043. Analysis of genotype combinations of ACT rs4343 polymorphism and hepatic lipase gene (UPC) rs1800588 showed that AA genotype of rs4343 polymorphism in combination with CC genotype of rs1800588 polymorphism was associated with lowest risk of renal dysfunction, whereas GG and AG genotypes of ACT rs4343 in combination with TT and CT genotypes of UPC rs1800588 - with the highest risk. Analysis of combinations of genotypes for three loci (ACE rs4291 and rs4343, UPC rs1800588) revealed that combination of risk genotypes of three genetic variants led to increase of odds ratio up to 4.42 [1.37-14.26], p=0.012. Conclusion. In STEMI patients an association was found between reduced GFR and TT genotype of ACE gene rs4291, as well as genotype combinations of ACT gene rs4291, rs4343 and UPC gene rs1800588. Higher odds ratios obtained with combination of «risk» genotypes of three polymorphisms demonstrated additive effects of genetic loci on the studied trait. Source


Karetnikova V.N.,Kemerovo State Medical Academy | Osokina A.V.,Kemerovo State Medical Academy | Evseeva M.V.,Kemerovo State Medical Academy | Gruzdeva O.V.,Research Institute for Complex Problems of Cardiovascular Diseases | And 6 more authors.
Kardiologiya | Year: 2016

Aim: to assess value for inhospital and 1 year prognosis of unfavorable course of ST-elevation myocardial infarction (STEMI) of blood serum galectin and markers of renal dysfunction (RD). Material and methods: Standard laboratory and instrumental examination, calculation of glomerular filtration rate using MDRD formula and by cystatin C level, determination of galectin in blood serum were carried out in 128 patients with STEMI. According to GFR by cystatin C level on day 12 of STEMI patients were divided into 2 groups - with normal renal function (GFR ≥60 ml/min/1.73 m2, n=47) and with RD (GFR <60 ml/min/1.73 m2, n = 81). Results and conclusion: In patients with STEMI presence of RD (lowering of GFR by cystatin C, by blood serum creatinine <60 ml/min/1.73 m2, creatinine clearance <60 ml/min), and elevation of galectin concentration > 17.8 hg/ml on day 12 of STEMI were independent predictors of unfavorable 1 year prognosis. Elevation of galectin level directly correlated with presence of early postinfarction angina. Source

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