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Epigenetics atherosclerosis

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
Jenneke Leentjens, Siroon Bekkering, Leo A 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 (ASCVD). 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 pro-inflammatory phenotype after brief stimulation with micro-organisms or microbial products, which has been termed trained immunity...
January 24, 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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28978221/epigenetics-and-trained-immunity
#13
Charlotte D van der Heijden, Marlies P Noz, Leo A B Joosten, Mihai G Netea, Niels P Riksen, Samuel T Keating
SIGNIFICANCE: A growing body of clinical and experimental evidence has challenged the traditional understanding that only the adaptive immune system can mount immunological memory. Recent findings describe the adaptive characteristics of the innate immune system, underscored by its ability to remember antecedent foreign encounters and respond in a nonspecific sensitized manner to reinfection. This has been termed trained innate immunity. Although beneficial in the context of recurrent infections, this might actually contribute to chronic immune-mediated diseases, such atherosclerosis...
October 5, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28971272/monocyte-and-macrophage-immunometabolism-in-atherosclerosis
#14
REVIEW
Laszlo Groh, Samuel T Keating, Leo A B Joosten, Mihai G Netea, Niels P Riksen
Atherosclerosis is characterized by chronic low grade inflammation of arteries that results in the development of lipid dense plaques. Chronic inflammation induced by Western-type diet is associated with the risk of developing atherosclerosis, and new insights shed light on the importance of metabolic and functional reprogramming in monocytes and macrophages for progression of atherosclerosis. This review aims to provide an overview of our current understanding into how the metabolic reprogramming of glucose, cholesterol, fatty acid, and amino acid metabolism in macrophages contributes to inflammation during atherosclerosis...
October 2, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28957329/uncovering-the-dna-methylation-landscape-in-key-regulatory-regions-within-the-fads-cluster
#15
Elaheh Rahbar, Hannah C Ainsworth, Timothy D Howard, Gregory A Hawkins, Ingo Ruczinski, Rasika Mathias, Michael C Seeds, Susan Sergeant, James E Hixson, David M Herrington, Carl D Langefeld, Floyd H Chilton
Genetic variants near and within the fatty acid desaturase (FADS) cluster are associated with polyunsaturated fatty acid (PUFA) biosynthesis, levels of several disease biomarkers and risk of human disease. However, determining the functional mechanisms by which these genetic variants impact PUFA levels remains a challenge. Utilizing an Illumina 450K array, we previously reported strong allele-specific methylation (ASM) associations (p = 2.69×10-29) between a single nucleotide polymorphism (SNP) rs174537 and DNA methylation of CpG sites located in the putative enhancer region between FADS1 and FADS2, in human liver tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28940884/involvement-of-pdgf-ligands-and-receptors-in-tumorigenesis
#16
REVIEW
Carl-Henrik Heldin, Johan Lennartsson, Bengt Westermark
Platelet-derived growth factor (PDGF) isoforms and their receptors have important roles during embryogenesis, particularly in the development of various mesenchymal cell types in different organs. In the adult, PDGF stimulates wound healing and regulates tissue homeostasis. However, over-activity of PDGF signaling is associated with malignancies and other diseases characterized by excessive cell proliferation, such as fibrotic conditions and atherosclerosis. In certain tumors, genetic or epigenetic alterations of the genes for PDGF ligands and receptors drives tumor cell proliferation and survival...
September 22, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28935756/perinatal-hypercholesterolemia-exacerbates-atherosclerosis-lesions-in-offspring-by-altering-metabolism-of-trimethylamine-n-oxide-and-bile-acids
#17
Charlotte Trenteseaux, Anh-Thu Gaston, Audrey Aguesse, Guillaume Poupeau, Pierre de Coppet, Ramaroson Andriantsitohaina, Jamila Laschet, Valérie Amarger, Michel Krempf, Estelle Nobecourt-Dupuy, Khadija Ouguerram
OBJECTIVE: Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. APPROACH AND RESULTS: Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers...
November 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28923781/low-dose-of-alcohol-attenuates-pro-atherosclerotic-activity-of-thrombin
#18
Masaaki Toda, Toshiaki Totoki, Chizu Nakamura, Taro Yasuma, Corina N D' Alessandro-Gabazza, Rumi Mifuji-Moroka, Kota Nishihama, Motoh Iwasa, Noriyuki Horiki, Esteban C Gabazza, Yoshiyuki Takei
BACKGROUND AND AIMS: Thrombin, the active enzyme of the coagulation system, plays a critical role in the pathogenesis of atherosclerosis. Vascular repair promoted by stromal cell-derived factor-1 is a protective process in atherosclerosis. Consumption of low amount of alcohol is believed to reduce the risk of atherosclerotic cardiovascular disease but the mechanism is unclear. This study evaluated whether alcohol can modulate the expression of stromal cell-derived factor-1 and the pro-atherosclerotic activity of thrombin...
September 5, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28910789/end-stage-renal-disease-inflammation-and-cardiovascular-outcomes
#19
Lu Dai, Edyta Golembiewska, Bengt Lindholm, Peter Stenvinkel
Despite marked improvements in renal replacement therapy during the last 30 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients is still unacceptably high and comparable to that of many malignancies. Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in ESRD patients. However, traditional risk factors can only partially explain the high premature cardiovascular burden in this population. Nontraditional risk factors, including persistent low-grade inflammation, are critical in the pathogenesis of atherosclerosis, vascular calcification, and other causes of CVD and may also contribute to protein-energy wasting and other complications in chronic kidney disease (CKD) patients...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28883714/vascular-aging-and-subclinical-atherosclerosis-why-such-a-never-ending-and-challenging-story-in-cardiology
#20
EDITORIAL
Stela Iurciuc, Anca Maria Cimpean, Florin Mitu, Rodica Heredea, Mircea Iurciuc
The true onset of atherosclerosis remains one of the biggest challenges for cardiologists. Is atheroma plaque development considered the earliest step of vascular aging? If so, when it starts? Before or after birth? If it starts before birth or early during childhood, it seems that Thomas Sydenham was right: "A man is as old as his arteries." Except disorganization of elastic fibers, less is known about the morphology of vascular aging and also about the molecular events influencing the age of arteries, arterial stiffness, and their role in the appearance of future complications...
2017: Clinical Interventions in Aging
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