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Search Results: 1 - 10 of 133440 matches for " Yuri V. Bobryshev "
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Perceptions and Opinions towards Cell Phone Use as a Risk Factor of Brain Cancer among University Students in Malaysia
Redhwan Ahmed Al-Naggar, Yuri V Bobryshev
Asian Journal of Medical Sciences , 2013, DOI: 10.3126/ajms.v4i1.7808
Abstract: The worldwide use of cell phones has rapidly increased over the past decades. With the increasing use of mobile phones, concern has been raised about the possible carcinogenic effects as a result of exposure to radiofrequency electromagnetic fields. The objective of this study was to explore the perceptions and opinions towards brain cancer related to cell phone use among university students in Malaysia. The study revealed that the majority of the study participants believe that there is no relationship between brain cancer and hand phone use. DOI: http://dx.doi.org/10.3126/ajms.v4i1.7808 Asian Journal of Medical Sciences 4(2013) 1-4
Mitochondrial Mutations are Associated with Atherosclerotic Lesions in the Human Aorta
Igor A. Sobenin,Margarita A. Sazonova,Anton Y. Postnov,Yuri V. Bobryshev,Alexander N. Orekhov
Clinical and Developmental Immunology , 2012, DOI: 10.1155/2012/832464
Abstract: Somatic mutations of the human mitochondrial genome can be a possible determinant of atherosclerosis. To test this possibility, forty mitochondrial mutations were analyzed in the present study in order to see which of these mutations might be associated with atherosclerosis. Ten mitochondrial mutations belonging to mitochondrial genes MT-RNR1 (rRNA 12S); MT-TL1 (tRNA-Leu, recognizes UUR); MT-TL2 (tRNA-Leu, recognizes CUN); MT-ND1, MT-ND2, MT-ND5, and MT-ND6 (subunits 1, 2, 5, and 6, respectively, of NADH dehydrogenase); and MT-CYB (cytochrome b) were potentially associated with atherosclerosis. From 29% (2 of 7 aortic samples) upto 86% (6 of 7 aortic samples) of aortic samples had a significant difference between atherosclerotic plaques and unaffected tissue, with the respect to the level of heteroplasmy for each mutation. Further, the homogenates of affected and normal intimae of 22 aortas were compared to reveal the average level of heteroplasmy for the above-mentioned 10 mutations. For five mutations, the mean level of heteroplasmy was significantly different in atherosclerotic intimal homogenates in comparison with the unaffected tissue. These mutations were A1555G, C3256T, T3336C, G13513A, and G15059A. Thus, it was demonstrated that at least five mitochondrial mutations occurring in MT-RNR1, MT-TL1, MT-ND2, MT-ND5, and MT-CYB genes are associated with atherosclerosis.
Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes
Dimitry A Chistiakov,Igor A Sobenin,Yuri V Bobryshev,Alexander N Orekhov
World Journal of Cardiology , 2012, DOI: 10.4330/wjc.v4.i5.148
Abstract: Mitochondrial DNA (mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system. This explains an increased mutation rate of mtDNA that results in heteroplasmy, e.g., the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion. In diabetes mellitus, glycotoxicity, advanced oxidative stress, collagen cross-linking, and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction, which in turn further contributes to the oxidative damage of the diabetic vascular wall, endothelial dysfunction, and atherosclerosis.
Mitochondrial Mutations are Associated with Atherosclerotic Lesions in the Human Aorta
Igor A. Sobenin,Margarita A. Sazonova,Anton Y. Postnov,Yuri V. Bobryshev,Alexander N. Orekhov
Journal of Immunology Research , 2012, DOI: 10.1155/2012/832464
Abstract: Somatic mutations of the human mitochondrial genome can be a possible determinant of atherosclerosis. To test this possibility, forty mitochondrial mutations were analyzed in the present study in order to see which of these mutations might be associated with atherosclerosis. Ten mitochondrial mutations belonging to mitochondrial genes MT-RNR1 (rRNA 12S); MT-TL1 (tRNA-Leu, recognizes UUR); MT-TL2 (tRNA-Leu, recognizes CUN); MT-ND1, MT-ND2, MT-ND5, and MT-ND6 (subunits 1, 2, 5, and 6, respectively, of NADH dehydrogenase); and MT-CYB (cytochrome b) were potentially associated with atherosclerosis. From 29% (2 of 7 aortic samples) upto 86% (6 of 7 aortic samples) of aortic samples had a significant difference between atherosclerotic plaques and unaffected tissue, with the respect to the level of heteroplasmy for each mutation. Further, the homogenates of affected and normal intimae of 22 aortas were compared to reveal the average level of heteroplasmy for the above-mentioned 10 mutations. For five mutations, the mean level of heteroplasmy was significantly different in atherosclerotic intimal homogenates in comparison with the unaffected tissue. These mutations were A1555G, C3256T, T3336C, G13513A, and G15059A. Thus, it was demonstrated that at least five mitochondrial mutations occurring in MT-RNR1, MT-TL1, MT-ND2, MT-ND5, and MT-CYB genes are associated with atherosclerosis. 1. Introduction Atherosclerosis underlies the development of most cardiovascular diseases, which are the leading cause of death in the 21st century. The mechanisms involved in the development of atherosclerosis have been intensively studied and various mechanisms and factors responsible for atherosclerotic alteration of the arterial intima have been suggested. Accumulating evidence supports an autoimmune mechanism as one of the prime pathogenic processes involved in the development of atherosclerosis [1–4]. Recently we suggested that somatic mutations within the mitochondrial genome may be a probable cause of atherosclerosis development in humans [5]. In humans, the mitochondrial DNA (mtDNA) spans 16,569 DNA base pairs and is represented by a two-stranded circular molecule containing 37 genes. The two strands of mtDNA are differentiated by their nucleotide content, with the guanine-rich strand referred to as the heavy strand, and the cytosine-rich strand referred to as the light strand. The heavy strand encodes 28 genes, and the light strand encodes 9 genes. Of a total of 37 genes, 13 genes encode proteins (polypeptides), 22 genes encode transfer RNAs (tRNAs), and 2 genes encode the
Association of Mitochondrial Genetic Variation with Carotid Atherosclerosis
Igor A. Sobenin, Margarita A. Sazonova, Anton Y. Postnov, Jukka T. Salonen, Yuri V. Bobryshev, Alexander N. Orekhov
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068070
Abstract: In human pathology, several diseases are associated with somatic mutations in the mitochondrial genome (mtDNA). Even though mitochondrial dysfunction leads to increased oxidative stress, the role of mitochondrial mutations in atherosclerosis has not received much attention so far. In this study we analyzed the association of mitochondrial genetic variation with the severity of carotid atherosclerosis, as assessed by carotid intima-media thickness (cIMT) and the presence of coronary heart disease (CHD) in 190 subjects from Moscow, Russia, a population with high CHD occurrence. cIMT was measured by high-resolution B-mode ultrasonography and mtDNA heteroplasmies by a pyrosequencing-based method. We found that heteroplasmies for several mutations in the mtDNA in leukocytes, including C3256T, T3336C, G12315A, G13513A, G14459A, G14846A, and G15059A mutations, were significantly (p<0.001) associated with both the severity of carotid atherosclerosis and the presence of CHD. These findings indicate that somatic mitochondrial mutations have a role in the development of atherosclerosis.
TRAIL-Deficiency Accelerates Vascular Calcification in Atherosclerosis via Modulation of RANKL
Belinda A. Di Bartolo, Sian P. Cartland, Hanis H. Harith, Yuri V. Bobryshev, Michael Schoppet, Mary M. Kavurma
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0074211
Abstract: The osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) cytokine system, not only controls bone homeostasis, but has been implicated in regulating vascular calcification. TNF–related apoptosis-inducing ligand (TRAIL) is a second ligand for OPG, and although its effect in vascular calcification in vitro is controversial, its role in vivo is not yet established. This study aimed to investigate the role of TRAIL in vascular calcification in vitro using vascular smooth muscle cells (VSMCs) isolated from TRAIL?/? and wild-type mice, as well as in vivo, in advanced atherosclerotic lesions of TRAIL?/?ApoE?/? mice. The involvement of OPG and RANKL in this process was also examined. TRAIL dose-dependently inhibited calcium-induced calcification of human VSMCs, while TRAIL?/? VSMCs demonstrated accelerated calcification induced by multiple concentrations of calcium compared to wild-type cells. Consistent with this, RANKL mRNA was significantly elevated with 24 h calcium treatment, while OPG and TRAIL expression in human VSMCs was inhibited. Brachiocephalic arteries from TRAIL?/?ApoE?/? and ApoE?/? mice fed a high fat diet for 12 w demonstrated increased chondrocyte-like cells in atherosclerotic plaque, as well as increased aortic collagen II mRNA expression in TRAIL?/?ApoE?/? mice, with significant increases in calcification observed at 20 w. TRAIL?/?ApoE?/? aortas also had significantly elevated RANKL, BMP-2, IL-1β, and PPAR-γ expression at 12 w. Our data provides the first evidence that TRAIL deficiency results in accelerated cartilaginous metaplasia and calcification in atherosclerosis, and that TRAIL plays an important role in the regulation of RANKL and inflammatory markers mediating bone turn over in the vasculature.
Mutation C3256T of Mitochondrial Genome in White Blood Cells: Novel Genetic Marker of Atherosclerosis and Coronary Heart Disease
Igor A. Sobenin, Margarita A. Sazonova, Maria M. Ivanova, Andrey V. Zhelankin, Veronika A. Myasoedova, Anton Y. Postnov, Serik D. Nurbaev, Yuri V. Bobryshev, Alexander N. Orekhov
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046573
Abstract: This study was undertaken to examine the association between the level of heteroplasmy for the mutation C3256T in human white blood cells and the extent of carotid atherosclerosis, as well as the presence of coronary heart disease (CHD), the major clinical manifestation of atherosclerosis. Totally, 191 participants (84 men, 107 women) aged 65.0 years (SD 9.4) were recruited in the study; 45 (24%) of them had CHD. High-resolution B-mode ultrasonography of carotids was used to estimate the extent of carotid atherosclerosis by measuring of the carotid intima-media thickness (cIMT). DNA samples were obtained from whole venous blood, and then PCR and pyrosequencing were carried out. On the basis of pyrosequencing data, the levels of C3256T heteroplasmy in DNA samples were calculated. The presence of the mutant allele was detected in all study participants; the level of C3256T heteroplasmy in white blood cells ranged from 5% to 74%. The highly significant relationship between C3256T heteroplasmy level and predisposition to atherosclerosis was revealed. In individuals with low predisposition to atherosclerosis the mean level of C3256T heteroplasmy was 16.8%, as compared to 23.8% in moderately predisposed subjects, and further to 25.2% and 28.3% in significantly and highly predisposed subjects, respectively. The level of C3256T heteroplasmy of mitochondrial genome in human white blood cells is a biomarker of mitochondrial dysfunction and risk factor for atherosclerosis; therefore, it can be used as an informative marker of genetic susceptibility to atherosclerosis, coronary heart disease and myocardial infarction.
Lipid Regulators during Atherogenesis: Expression of LXR, PPAR, and SREBP mRNA in the Human Aorta
Tatyana A. Shchelkunova, Ivan A. Morozov, Petr M. Rubtsov, Yuri V. Bobryshev, Igor A. Sobenin, Alexander N. Orekhov, Irina V. Andrianova, Alexander N. Smirnov
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063374
Abstract: Transcription factors LXRs, PPARs, and SREBPs have been implicated in a multitude of physiological and pathological processes including atherogenesis. However, little is known about the regulation of these transcription factors at different stages of atherosclerosis progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to compare the contents of mRNAs in pairs intact-injured aorta fragments taken from the same donors. Only minor changes in LXRα, LXRβ, PPARα, PPARγ, SREBP1, and SREBP2 mRNA levels were found in initial lesions as compared with intact non-diseased tissue. The contents of all mRNAs but SREBP2 mRNA were found to be progressively up-regulated in fatty streaks and fibrous lipoid plaques. These changes were only partially reproduced in cultured macrophages upon lipid loading. Wave-shaped changes in abundance of correlations between given group of mRNAs and 28 atherosclerosis-related mRNA species in the course of atherogenesis were observed. The impact of specific mRNA correlations on the total correlations also significantly varied between different lesion types. The study suggests that the extent and forms of LXR/PPAR/SREBP participation in intima functions vary nonlinear in individual fashion in atherogenesis. We speculate that the observed changes in mRNAs expression and coupling reflect shifts in lipid ligands availability and cellular composition in the course of atherosclerosis progression.
Human Immunodeficiency Virus Impairs Reverse Cholesterol Transport from Macrophages
Zahedi Mujawar,Honor Rose,Matthew P. Morrow,Tatiana Pushkarsky,Larisa Dubrovsky,Nigora Mukhamedova,Ying Fu,Anthony Dart,Jan M. Orenstein,Yuri V. Bobryshev,Michael Bukrinsky,Dmitri Sviridov
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0040365
Abstract: Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from human macrophages, a condition previously shown to be highly atherogenic. In HIV-1–infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells. At least two mechanisms were found to be responsible for this phenomenon: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. HIV-infected and Nef-transfected macrophages accumulated substantial amounts of lipids, thus resembling foam cells. The contribution of HIV-infected macrophages to the pathogenesis of atherosclerosis was supported by the presence of HIV-positive foam cells in atherosclerotic plaques of HIV-infected patients. Stimulation of cholesterol efflux from macrophages significantly reduced infectivity of the virions produced by these cells, and this effect correlated with a decreased amount of virion-associated cholesterol, suggesting that impairment of cholesterol efflux is essential to ensure proper cholesterol content in nascent HIV particles. These results reveal a previously unrecognized dysregulation of intracellular lipid metabolism in HIV-infected macrophages and identify Nef and ABCA1 as the key players responsible for this effect. Our findings have implications for pathogenesis of both HIV disease and atherosclerosis, because they reveal the role of cholesterol efflux impairment in HIV infectivity and suggest a possible mechanism by which HIV infection of macrophages may contribute to increased risk of atherosclerosis in HIV-infected patients.
Human Immunodeficiency Virus Impairs Reverse Cholesterol Transport from Macrophages
Zahedi Mujawar equal contributor,Honor Rose equal contributor,Matthew P Morrow,Tatiana Pushkarsky,Larisa Dubrovsky,Nigora Mukhamedova,Ying Fu,Anthony Dart,Jan M Orenstein,Yuri V Bobryshev,Michael Bukrinsky ,Dmitri Sviridov
PLOS Biology , 2006, DOI: 10.1371/journal.pbio.0040365
Abstract: Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from human macrophages, a condition previously shown to be highly atherogenic. In HIV-1–infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells. At least two mechanisms were found to be responsible for this phenomenon: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. HIV-infected and Nef-transfected macrophages accumulated substantial amounts of lipids, thus resembling foam cells. The contribution of HIV-infected macrophages to the pathogenesis of atherosclerosis was supported by the presence of HIV-positive foam cells in atherosclerotic plaques of HIV-infected patients. Stimulation of cholesterol efflux from macrophages significantly reduced infectivity of the virions produced by these cells, and this effect correlated with a decreased amount of virion-associated cholesterol, suggesting that impairment of cholesterol efflux is essential to ensure proper cholesterol content in nascent HIV particles. These results reveal a previously unrecognized dysregulation of intracellular lipid metabolism in HIV-infected macrophages and identify Nef and ABCA1 as the key players responsible for this effect. Our findings have implications for pathogenesis of both HIV disease and atherosclerosis, because they reveal the role of cholesterol efflux impairment in HIV infectivity and suggest a possible mechanism by which HIV infection of macrophages may contribute to increased risk of atherosclerosis in HIV-infected patients.
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