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Epigenetics atherosclerosis

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https://www.readbyqxmd.com/read/29678824/metabolic-karma-the-atherogenic-legacy-of-diabetes-the-2017-edwin-bierman-award-lecture
#1
Mark Emmanuel Cooper, Assam El-Osta, Terri Jean Allen, Anna Margareta Dorothea Watson, Merlin Christopher Thomas, Karin Agnes Maria Jandeleit-Dahm
Cardiovascular disease, despite all the recent advances in treatment of the various risk factors, remains the major cause of mortality in both type 1 and type 2 diabetes. Experimental models of diabetes-associated atherosclerosis, despite their limitations in recapitulating the human context, have assisted in the elucidation of molecular and cellular pathways implicated in the development and progression of macrovascular injury in diabetes. Our own studies have emphasized the role of oxidative stress and advanced glycation and identified potential targets for vasoprotective therapies in the setting of diabetes...
May 2018: Diabetes
https://www.readbyqxmd.com/read/29653065/tet2-a-novel-epigenetic-regulator-and-potential-intervention-target-for-atherosclerosis
#2
Yami Liu, Wen Peng, Kai Qu, Xiaolong Lin, Zhaolin Zeng, Jiaojiao Chen, Dangheng Wei, Zuo Wang
Atherosclerosis is the underlying cause of cardio-cerebrovascular disease. However, the mechanisms of atherosclerosis are still unclear. The modification of DNA methylation has an important role in atherosclerosis development. As a member of the Ten-eleven translocation (TET) family, TET methylcytosine dioxygenase 2 (TET2) can modify DNA methylation by catalyzing 5-methylcytosine to 5-hydroxymethylcytosine and mediate DNA demethylation. Recent findings suggest that TET2 is related to the phenotype transformation of vascular smooth muscle cells, endothelial dysfunction, and inflammation of macrophage, the key factors of atherosclerosis...
April 13, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29609002/angiotensin-ii-facilitates-neointimal-formation-by-increasing-vascular-smooth-muscle-cell-migration-involvement-of-ape-ref-1-mediated-overexpression-of-sphingosine-1-phosphate-receptor-1
#3
Dong-Youb Lee, Kyung-Jong Won, Kang Pa Lee, Seung Hyo Jung, Suji Baek, Hyun Woo Chung, Wahn Soo Choi, Hwan Myung Lee, Byeong Han Lee, Byeong Hwa Jeon, Bokyung Kim
Angiotensin II (Ang II) is implicated in the development of cardiovascular disorders including hypertension and atherosclerosis. However, the role of Ang II in the interaction between apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) and sphingosine-1-phosphate (S1P) signals in relation to vascular disorders remains to be clarified. This study aimed to determine whether APE/Ref-1 plays a role in epigenetic regulation of the S1P receptor (S1PR) in response to Ang II in vascular smooth muscle cell (VSMC) migration and vascular neointima formation...
March 30, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29555670/prospective-study-of-epigenetic-age-acceleration-and-incidence-of-cardiovascular-disease-outcomes-in-the-aric-study-atherosclerosis-risk-in-communities
#4
Nicholas S Roetker, James S Pankow, Jan Bressler, Alanna C Morrison, Eric Boerwinkle
BACKGROUND: DNA methylation-based patterns of biological aging, known as epigenetic age acceleration, are predictive of all-cause mortality, but little is known about their association with cardiovascular disease (CVD). METHODS: We estimated 2 versions of epigenetic age acceleration (Horvath and Hannum) using whole-blood samples from 2543 blacks. Linear and Cox proportional hazards regression, respectively, were used to assess the association of age acceleration with carotid intima-media thickness (cross-sectionally) and incident cardiovascular events, including CVD mortality, myocardial infarction, fatal coronary heart disease, peripheral arterial disease, and heart failure, during a median 21-year follow-up...
March 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29534238/targeting-epigenetic-dna-and-histone-modifications-to-treat-kidney-disease
#5
Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Maria Dolores Sanchez-Niño, Lara Valiño-Rivas, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease...
March 9, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29511860/dj-1-is-involved-in-epigenetic-control-of-sphingosine-1-phosphate-receptor-expression-in-vascular-neointima-formation
#6
Kang Pa Lee, Suji Baek, Seung Hyo Jung, Long Cui, Donghyen Lee, Dong-Youb Lee, Wahn Soo Choi, Hyun Woo Chung, Byeong Han Lee, Bokyung Kim, Kyung Jong Won
DJ-1 and sphingosine-1-phosphate (S1P) receptors (S1PRs) are implicated in the control of physiology and pathophysiology of cardiovascular systems such as blood pressure, atherosclerosis, and restenosis. Here, we investigated whether DJ-1 with antioxidant function participates in the regulation of S1PR1 and S1PR2 expression in vascular smooth muscle cells (VSMCs) and whether this response is related to vascular neointima formation. In vitro studies used cellular migration assay, western blot, reverse transcriptase and real-time PCR analysis, and immunocytochemistry...
March 6, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29498880/-long-non-coding-rnas-in-the-pathophysiology-of-atherosclerosis
#7
Jan Novak, Julie Bienertová Vašků, Miroslav Souček
The human genome contains about 22 000 protein-coding genes that are transcribed to an even larger amount of messenger RNAs (mRNA). Interestingly, the results of the project ENCODE from 2012 show, that despite up to 90 % of our genome being actively transcribed, protein-coding mRNAs make up only 2-3 % of the total amount of the transcribed RNA. The rest of RNA transcripts is not translated to proteins and that is why they are referred to as "non-coding RNAs". Earlier the non-coding RNA was considered "the dark matter of genome", or "the junk", whose genes has accumulated in our DNA during the course of evolution...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29498708/identification-and-characterizations-of-novel-selective-histone-methyltransferase-set7-inhibitors-by-scaffold-hopping-and-2d-molecular-fingerprint-based-similarity-search
#8
Hong Ding, Wen Chao Lu, Jun Chi Hu, Yu-Chih Liu, Chen Hua Zhang, Fu Lin Lian, Nai Xia Zhang, Fan Wang Meng, Cheng Luo, Kai Xian Chen
SET7, serving as the only histone methyltransferase that monomethylates 'Lys-4' of histone H3, has been proved to function as a key regulator in diverse biological processes, such as cell proliferation, transcriptional network regulation in embryonic stem cell, cell cycle control, protein stability, heart morphogenesis and development. What's more, SET7 is involved inthe pathogenesis of alopecia aerate, breast cancer, tumor and cancer progression, atherosclerosis in human carotid plaques, chronic renal diseases, diabetes, obesity, ovarian cancer, prostate cancer, hepatocellular carcinoma, and pulmonary fibrosis...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29438482/the-lipodystrophic-hotspot-lamin-a-p-r482w-mutation-deregulates-the-mesodermal-inducer-t-brachyury-and-early-vascular-differentiation-gene-networks
#9
Nolwenn Briand, Anne-Claire Guénantin, Dorota Jeziorowska, Akshay Shah, Matthieu Mantecon, Emilie Capel, Marie Garcia, Anja Oldenburg, Jonas Paulsen, Jean-Sebastien Hulot, Corinne Vigouroux, Philippe Collas
The p.R482W hotspot mutation in A-type nuclear lamins causes familial partial lipodystrophy of Dunnigan-type (FPLD2), a lipodystrophic syndrome complicated by early-onset atherosclerosis. Molecular mechanisms underlying endothelial cell dysfunction conferred by the lamin A mutation remain elusive. However, lamin A regulates epigenetic developmental pathways and mutations could perturb these functions. Here, we demonstrate that lamin A R482W elicits endothelial differentiation defects in a developmental model of FPLD2...
February 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29436575/identification-of-novel-hyper-%C3%A2-or-hypomethylated-cpg-sites-and-genes-associated-with-atherosclerotic-plaque-using-an-epigenome-wide-association-study
#10
Yoshiji Yamada, Hideki Horibe, Mitsutoshi Oguri, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Motoji Sawabe
DNA methylation is an important epigenetic modification that has been implicated in the pathogenesis of atherosclerosis. Although previous studies have identified various CpG sites and genes whose methylation is associated with atherosclerosis in populations with European or Mexican ancestry, the genome‑wide pattern of DNA methylation in the atherosclerotic human aorta is yet to be elucidated in Japanese individuals. In the present study, a genome‑wide analysis of DNA methylation at ~853,000 CpG sites was performed using 128 postmortem aortic intima specimens obtained from 64 Japanese patients...
February 2, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29425287/perinatal-bisphenol-a-exposure-increases-atherosclerosis-in-adult-male-pxr-humanized-mice
#11
Yipeng Sui, Se-Hyung Park, Fang Wang, Changcheng Zhou
Bisphenol A (BPA) is a base chemical used extensively in numerous consumer products, and human exposure to BPA is ubiquitous. Higher BPA exposure has been associated with increased risk of atherosclerosis and cardiovascular disease (CVD) in multiple human population-based studies, but the underlying mechanisms responsible for the associations remain elusive. We previously reported that BPA activates the xenobiotic receptor pregnane X receptor (PXR) which has pro-atherogenic effects in animal models. Since BPA is a potent agonist for human PXR but does not affect rodent PXR activity, a suitable PXR-humanized Apolipoprotein E-deficient (huPXR•ApoE-/-) mouse model was developed to study BPA's atherogenic effects, and chronic BPA exposure indeed increased atherosclerosis in huPXR•ApoE-/- mice...
February 7, 2018: Endocrinology
https://www.readbyqxmd.com/read/29411649/alteration-in-microrna-155-level-correspond-to-severity-of-coronary-heart-disease
#12
Xian-Ke Qiu, Jun Ma
Cardiovascular diseases are a consequence of genetic and epigenetic interactions. Inflammation contributes toward the initiation and progression of atherosclerotic lesions. Previous studies have shown that microRNA (miR) 155 plays a role in cardiovascular disease, including the prevention of inflammatory infiltration, regulation of autophagy, and participation of immunoreactions. However, the change of miR-155 level in the development of atherosclerosis remains to be determined. The initial objective of this study was that CHD patients would have altered serum miR-155 level...
February 7, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29410709/genomic-5-mc-contents-in-peripheral-blood-leukocytes-were-independent-protective-factors-for-coronary-artery-disease-with-a-specific-profile-in-different-leukocyte-subtypes
#13
Qianyun Deng, Wei Huang, Chunyan Peng, Jiajia Gao, Zuhua Li, Xueping Qiu, Na Yang, Bifeng Yuan, Fang Zheng
Background: Alterations in DNA methylation are demonstrated in atherosclerosis pathogenesis. However, changing rules of global DNA methylation and hydroxymethylation in peripheral blood leukocytes (PBLs) and different blood cell subtypes of coronary artery disease (CAD) patients are still inconclusive, and much less is known about mechanisms underlying. Results: We recruited 265 CAD patients and 270 healthy controls with genomic DNA from PBLs, of which 50 patients and 50 controls were randomly chosen with DNA from isolated neutrophils, lymphocytes and monocytes, and RNA from PBLs...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29383092/identification-of-the-histone-lysine-demethylase-kdm4a-jmjd2a-as-a-novel-epigenetic-target-in-m1-macrophage-polarization-induced-by-oxidized-ldl
#14
Xue Wang, Siqing Wang, Gang Yao, Dehai Yu, Kexin Chen, Qian Tong, Long Ye, Chuan Wu, Yue Sun, Haixia Li, Dirk M Hermann, Thorsten R Doeppner, Fengyan Jin, Yun Dai, Jiang Wu
Oxidized low density lipoprotein (oxLDL) induces macrophage activation, an event essential for atherosclerosis. Emerging evidence supports that epigenetic regulation plays important roles in macrophage activation and function. However, it remains unclear which epigenetic modulator is responsible for oxLDL-induced macrophage activation. Here, we identify for the first time KDM4A (JMJD2A) as an epigenetic modifying enzyme that controls oxLDL-induced pro-inflammatory M1 polarization of macrophages. OxLDL triggered M1 polarization of murine and human macrophages, characterized by expression of iNOS and robust production of inflammatory cytokines (e...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29367213/trained-innate-immunity-as-a-novel-mechanism-linking-infection-and-the-development-of-atherosclerosis
#15
REVIEW
Jenneke Leentjens, Siroon Bekkering, Leo A B Joosten, Mihai G Netea, David P Burgner, Niels P Riksen
RATIONALE: There is strong epidemiological evidence for an association between acute and chronic infections and the occurrence of atherosclerotic cardiovascular disease. The underlying pathophysiological mechanisms remain unclear. Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. It has recently been established that monocytes/macrophages can develop a long-lasting proinflammatory phenotype after brief stimulation with micro-organisms or microbial products, which has been termed trained immunity...
March 2, 2018: Circulation Research
https://www.readbyqxmd.com/read/29343087/sulfhydrated-sirtuin-1-increasing-its-deacetylation-activity-is-an-essential-epigenetics-mechanism-of-anti-atherogenesis-by-hydrogen-sulfide
#16
Congkuo Du, Xianjuan Lin, Wenjing Xu, Fengjiao Zheng, Junyan Cai, Jichun Yang, Qinghua Cui, Chaoshu Tang, Jun Cai, Guoheng Xu, Bin Geng
AIMS: Hydrogen sulfide (H2S) has a protective role in the pathogenesis of atherosclerosis by multiple pathways. Sirtuin-1 (SIRT1) is a histone deacetylase, as an essential mediated longevity gene, and has an anti-atherogenic effect by regulating the acetylation of some functional proteins. Whether SIRT1 is involved in protecting H2S in atherosclerosis and its mechanism remains unclear. RESULTS: In ApoE-knockout atherosclerosis mice, treatment with an H2S donor (NaHS or GYY4137) reduced atherosclerotic plaque area, macrophage infiltration, aortic inflammation and plasma lipid level...
January 17, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29119010/epigenetic-impact-of-endocrine-disrupting-chemicals-on-lipid-homeostasis-and-atherosclerosis-a-pregnane-x-receptor-centric-view
#17
Robert N Helsley, Changcheng Zhou
Despite the major advances in developing diagnostic techniques and effective treatments, atherosclerotic cardiovascular disease (CVD) is still the leading cause of mortality and morbidity worldwide. While considerable progress has been achieved to identify gene variations and environmental factors that contribute to CVD, much less is known about the role of "gene-environment interactions" in predisposing individuals to CVD. Our chemical environment has significantly changed in the last few decades, and there are more than 100,000 synthetic chemicals in the market...
October 1, 2017: Environmental Epigenetics
https://www.readbyqxmd.com/read/29118325/the-mammalian-target-of-rapamycin-and-dna-methyltransferase-1-axis-mediates-vascular-endothelial-dysfunction-in-response-to-disturbed-flow
#18
Yun-Peng Zhang, Yi-Tao Huang, Tse-Shun Huang, Wei Pang, Juan-Juan Zhu, Yue-Feng Liu, Run-Ze Tang, Chuan-Rong Zhao, Wei-Juan Yao, Yi-Shuan Li, Shu Chien, Jing Zhou
The earliest atherosclerotic lesions preferentially develop in arterial regions experienced disturbed blood flow, which induces endothelial expression of pro-atherogenic genes and the subsequent endothelial dysfunction. Our previous study has demonstrated an up-regulation of DNA methyltransferase 1 (DNMT1) and a global hypermethylation in vascular endothelium subjected to disturbed flow. Here, we determined that DNMT1-specific inhibition in arterial wall ameliorates the disturbed flow-induced atherosclerosis through, at least in part, targeting cell cycle regulator cyclin A and connective tissue growth factor (CTGF)...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29045471/parental-and-offspring-contribution-of-genetic-markers-of-adult-blood-pressure-in-early-life-the-family-study
#19
Sébastien Robiou-du-Pont, Sonia S Anand, Katherine M Morrison, Sarah D McDonald, Stephanie A Atkinson, Koon K Teo, David Meyre
Previous genome wide association studies (GWAS) identified associations of multiple common variants with diastolic and systolic blood pressure traits in adults. However, the contribution of these loci to variations of blood pressure in early life is unclear. We assessed the child and parental contributions of 33 GWAS single-nucleotide polymorphisms (SNPs) for blood pressure in 1,525 participants (515 children, 406 mothers and 237 fathers) of the Family Atherosclerosis Monitoring In early life (FAMILY) study followed-up for 5 years...
2017: PloS One
https://www.readbyqxmd.com/read/29038540/regulation-of-endothelial-intracellular-adenosine-via-adenosine-kinase-epigenetically-modulates-vascular-inflammation
#20
Yiming Xu, Yong Wang, Siyuan Yan, Qiuhua Yang, Yaqi Zhou, Xianqiu Zeng, Zhiping Liu, Xiaofei An, Haroldo A Toque, Zheng Dong, Xuejun Jiang, David J Fulton, Neal L Weintraub, Qinkai Li, Zsolt Bagi, Mei Hong, Detlev Boison, Chaodong Wu, Yuqing Huo
The molecular mechanisms underlying vascular inflammation and associated inflammatory vascular diseases are not well defined. Here we show that endothelial intracellular adenosine and its key regulator adenosine kinase (ADK) play important roles in vascular inflammation. Pro-inflammatory stimuli lead to endothelial inflammation by increasing endothelial ADK expression, reducing the level of intracellular adenosine in endothelial cells, and activating the transmethylation pathway through increasing the association of ADK with S-adenosylhomocysteine (SAH) hydrolase (SAHH)...
October 16, 2017: Nature Communications
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