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Epigenetics atherosclerosis

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https://www.readbyqxmd.com/read/28104796/clonal-hematopoiesis-associated-with-tet2-deficiency-accelerates-atherosclerosis-development-in-mice
#1
José J Fuster, Susan MacLauchlan, María A Zuriaga, Maya N Polackal, Allison C Ostriker, Raja Chakraborty, Chia-Ling Wu, Soichi Sano, Sujatha Muralidharan, Cristina Rius, Jacqueline Vuong, Sophia Jacob, Varsha Muralidhar, Avril A B Robertson, Matthew A Cooper, Vicente Andrés, Karen K Hirschi, Kathleen A Martin, Kenneth Walsh
Human aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several of these recurrent mutations, including those in the gene encoding the epigenetic modifier enzyme TET2, promote expansion of the mutant blood cells. This "clonal hematopoiesis" correlates with an increased risk of atherosclerotic cardiovascular disease. Here we studied the effects of the expansion of Tet2-mutant cells in atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr-/-) mice. We found that partial bone marrow reconstitution with Tet2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size...
January 19, 2017: Science
https://www.readbyqxmd.com/read/28062506/wnt-signaling-pathway-inhibitor-sclerostin-inhibits-angiotensin-ii-induced-aortic-aneurysm-and-atherosclerosis
#2
Smriti Murali Krishna, Sai-Wang Seto, Roby J Jose, Jiaze Li, Susan K Morton, Erik Biros, Yutang Wang, Vianne Nsengiyumva, Jan H N Lindeman, Gabriela G Loots, Catherine M Rush, Jeffrey M Craig, Jonathan Golledge
OBJECTIVE: Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. APPROACH AND RESULTS: SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE(-/-)) mice (SOST(Tg)...
December 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28030845/withdrawn-could-some-epigenetic-modifications-hold-the-key-to-opposing-the-metabolic-syndrome
#3
REVIEW
Giovanni Tarantino, Matteo Nicola Di Minno, Carmine Finelli
Ahead of Print article withdrawn by publisher.
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029182/nedd4-deficiency-in-vascular-smooth-muscle-promotes-vascular-calcification-by-stabilizing-psmad1
#4
Ji-Hyun Lee, Seon-Ae Jeon, Byung-Gyu Kim, Michiko Takeda, Jae-Jin Cho, Dong-Ik Kim, Hiroshi Kawabe, Je-Yoel Cho
The nonosseous calcification process such as atherosclerosis is one of the major complications in several types of metabolic diseases. In previous study, we uncovered that aberrant activity of TGF-β signaling pathway could contribute the vascular smooth muscle cells (VSMCs) calcification process. Also, we identified NEDD4 E3 ligase as a key suppressor of BMP/Smad pathway via a polyubiquitination dependent selective degradation of C-terminal phosphorylated Smad1 (pSmad1) activated by TGF-β⋅ Here, we further validated and confirmed the role of Nedd4 in in vivo vascular calcification progression...
December 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27932351/telomerase-reverse-transcriptase-deficiency-prevents-neointima-formation-through-chromatin-silencing-of-e2f1-target-genes
#5
Elizabeth B Endorf, Hua Qing, Jun Aono, Naoto Terami, Geneviève Doyon, Eric Hyzny, Karrie L Jones, Hannes M Findeisen, Dennis Bruemmer
OBJECTIVE: Aberrant proliferation of smooth muscle cells (SMC) in response to injury induces pathological vascular remodeling during atherosclerosis and neointima formation. Telomerase is rate limiting for tissue renewal and cell replication; however, the physiological role of telomerase in vascular diseases remains to be determined. The goal of the present study was to determine whether telomerase reverse transcriptase (TERT) affects proliferative vascular remodeling and to define the molecular mechanism by which TERT supports SMC proliferation...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27904046/cocl2-decreases-ec-sod-expression-through-histone-deacetylation-in-cos7-cells
#6
Shuhei Hattori, Tetsuro Kamiya, Hirokazu Hara, Masayuki Ninomiya, Mamoru Koketsu, Tetsuo Adachi
Extracellular-superoxide dismutase (EC-SOD), one of the SOD isozymes, is negatively regulated under hypoxic conditions, and decreases in its expression may exacerbate vascular diseases. Moreover, epigenetics, such as DNA methylation and histone modifications, are known to play a critical role in the progression of cancer, type 2 diabetes, and atherosclerosis. We previously investigated the involvement of reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) in decreases in EC-SOD expression in hypoxic COS7 cells; however, the role of epigenetics in this process currently remains unknown...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27903268/long-term-outdoor-air-pollution-and-dna-methylation-in-circulating-monocytes-results-from-the-multi-ethnic-study-of-atherosclerosis-mesa
#7
Gloria C Chi, Yongmei Liu, James W MacDonald, R Graham Barr, Kathleen M Donohue, Mark D Hensley, Lifang Hou, Charles E McCall, Lindsay M Reynolds, David S Siscovick, Joel D Kaufman
BACKGROUND: DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55). METHODS: One-year average ambient fine particulate matter (PM2...
December 1, 2016: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/27869795/cd68-macrosialin-not-just-a-histochemical-marker
#8
Dimitry A Chistiakov, Murry C Killingsworth, Veronika A Myasoedova, Alexander N Orekhov, Yuri V Bobryshev
CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells...
November 21, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27765534/diabetic-nephropathy-and-endothelial-dysfunction-current-and-future-therapies-and-emerging-of-vascular-imaging-for-preclinical-renal-kinetic-study
#9
REVIEW
Wilson Kc Leung, L Gao, Parco M Siu, Christopher Wk Lai
An explosion in global epidemic of type 2 diabetes mellitus poses major rise in cases with vascular endothelial dysfunction ranging from micro- (retinopathy, nephropathy and neuropathy) to macro-vascular (atherosclerosis and cardiomyopathy) conditions. Functional destruction of endothelium is regarded as an early event that lays the groundwork for the development of renal microangiopathy and subsequent clinical manifestation of nephropathic symptoms. Recent research has shed some light on the molecular mechanisms of type 2 diabetes-associated comorbidity of endothelial dysfunction and nephropathy...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27764724/innate-immune-cell-activation-and-epigenetic-remodeling-in-symptomatic-and-asymptomatic-atherosclerosis-in-humans-in%C3%A2-vivo
#10
Siroon Bekkering, Inge van den Munckhof, Tim Nielen, Evert Lamfers, Charles Dinarello, Joost Rutten, Jacqueline de Graaf, Leo A B Joosten, Mihai G Netea, Marc E R Gomes, Niels P Riksen
BACKGROUND AND AIMS: We have recently reported that monocytes can undergo functional and transcriptional reprogramming towards a long-term pro-inflammatory phenotype after brief in vitro exposure to atherogenic stimuli such as oxidized LDL. This process is termed 'trained immunity', and is mediated by epigenetic remodeling and a metabolic switch towards increased aerobic glycolysis. We hypothesize that trained immunity contributes to atherogenesis. Therefore, we investigated the inflammatory phenotype and epigenetic remodeling of monocytes from patients with and without established atherosclerosis...
October 12, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27755984/mirna-27b-modulates-endothelial-cell-angiogenesis-by-directly-targeting-naa15-in-atherogenesis
#11
Li Qun, Xi Wenda, Sun Weihong, Ma Jianyang, Cai Wei, Lou Fangzhou, Xu Zhenyao, Gao Pingjin
BACKGROUND AND AIMS: The CCL20/CCR6 axis has been shown to play a vital role in the pathogenesis of atherosclerosis (AS). However, the regulatory mechanism remains unclear. Here, we studied the miRNA-mediated epigenetic regulation of the CCL20/CCR6 axis in atherogenesis. METHODS: CCR6(+/+)ApoE-/- and CCR6(-/-)ApoE-/- mice were fed a high-fat diet for 24 weeks. Plaque size was evaluated via ultrasound biomicroscope and hematoxylin and eosin. Protein expression were measured by Western blotting or immunofluorescence/immunohistochemistry or ELISA, and gene mRNA levels were detected by RT-PCR...
October 8, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27754176/sy-15-2-endothelial-epigenetics-and-its-role-in-mediating-biomechanical-stress-of-hypertension
#12
Peter F Davies, Elisabetta Manduchi, Christian J Stoeckert, Yi-Zhou Jiang
Hemodynamics creates a constantly changing physical and chemical environment to which the arterial endothelium is exquisitely sensitive. Biomechanical stresses are intrinsic to blood flow characteristics and blood pressure and therefore are important considerations in hypertension. Near branching anatomical sites in arteries, blood flow separates from the main flow to undergo complex multi-directional characteristics for a part of each cardiac cycle (collectively referred to as disturbed flow). Atherosclerosis and aneurysmal pathology develop preferentially at disturbed flow locations, particularly when an additional cardiovascular risk factor such as hypercholesterolemia or high blood pressure are present...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27726072/genetic-research-and-women-s-heart-disease-a-primer
#13
Maryam Kavousi, Lawrence F Bielak, Patricia A Peyser
PURPOSE OF REVIEW: This review provides a brief synopsis of sexual dimorphism in atherosclerosis with an emphasis on genetic studies aimed to better understand the atherosclerotic process and clinical outcomes in women. Such studies are warranted because development of atherosclerosis, impact of several traditional risk factors, and burden of coronary heart disease (CHD) differ between women and men. RECENT FINDINGS: While most candidate gene studies pool women and men and adjust for sex, some sex-specific studies provide evidence of association between candidate genes and prevalent and incident CHD in women...
November 2016: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/27643133/sy-15-2-endothelial-epigenetics-and-its-role-in-mediating-biomechanical-stress-of-hypertension
#14
Peter F Davies, Elisabetta Manduchi, Christian J Stoeckert, Yi-Zhou Jiang
Hemodynamics creates a constantly changing physical and chemical environment to which the arterial endothelium is exquisitely sensitive. Biomechanical stresses are intrinsic to blood flow characteristics and blood pressure and therefore are important considerations in hypertension. Near branching anatomical sites in arteries, blood flow separates from the main flow to undergo complex multi-directional characteristics for a part of each cardiac cycle (collectively referred to as disturbed flow). Atherosclerosis and aneurysmal pathology develop preferentially at disturbed flow locations, particularly when an additional cardiovascular risk factor such as hypercholesterolemia or high blood pressure are present...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27633111/improvements-in-metabolic-health-with-consumption-of-ellagic-acid-and-subsequent-conversion-into-urolithins-evidence-and-mechanisms
#15
REVIEW
Inhae Kang, Teresa Buckner, Neil F Shay, Liwei Gu, Soonkyu Chung
Ellagic acid (EA) is a naturally occurring polyphenol found in some fruits and nuts, including berries, pomegranates, grapes, and walnuts. EA has been investigated extensively because of its antiproliferative action in some cancers, along with its anti-inflammatory effects. A growing body of evidence suggests that the intake of EA is effective in attenuating obesity and ameliorating obesity-mediated metabolic complications, such as insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, and atherosclerosis...
September 2016: Advances in Nutrition
https://www.readbyqxmd.com/read/27570805/data-on-gene-and-protein-expression-changes-induced-by-apabetalone-rvx-208-in-ex-vivo-treated-human-whole-blood-and-primary-hepatocytes
#16
Sylwia Wasiak, Dean Gilham, Laura M Tsujikawa, Christopher Halliday, Karen Norek, Reena G Patel, Kevin G McLure, Peter R Young, Allan Gordon, Ewelina Kulikowski, Jan Johansson, Michael Sweeney, Norman C Wong
Apabetalone (RVX-208) inhibits the interaction between epigenetic regulators known as bromodomain and extraterminal (BET) proteins and acetyl-lysine marks on histone tails. Data presented here supports the manuscript published in Atherosclerosis "RVX-208, a BET-inhibitor for Treating Atherosclerotic Cardiovascular Disease, Raises ApoA-I/HDL and Represses Pathways that Contribute to Cardiovascular Disease" (Gilham et al., 2016) [1]. It shows that RVX-208 and a comparator BET inhibitor (BETi) JQ1 increase mRNA expression and production of apolipoprotein A-I (ApoA-I), the main protein component of high density lipoproteins, in primary human and African green monkey hepatocytes...
September 2016: Data in Brief
https://www.readbyqxmd.com/read/27560313/new-insights-into-molecular-mechanisms-of-epigenetic-regulation-in-kidney-disease
#17
REVIEW
Imari Mimura, Tetsuhiro Tanaka, Masaomi Nangaku
The number of patients with kidney failure has increased in recent years. Different factors contribute to the progression of chronic kidney disease, including glomerular sclerosis, atherosclerosis of the renal arteries and tubulointerstitial fibrosis. Tubulointerstitial injury is induced by hypoxia and other inflammatory signals, leading to fibroblast activation. Technological advances using high-throughput sequencing has enabled the determination of the expression profile of almost all genes, revealing that gene expression is intricately regulated by DNA methylation, histone modification, changes in chromosome conformation, long non-coding RNAs and microRNAs...
December 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27469259/diabetes-propels-the-risk-for-cardiovascular-disease-sweet-monocytes-becoming-aggressive
#18
REVIEW
Janna A van Diepen, Kathrin Thiem, Rinke Stienstra, Niels P Riksen, Cees J Tack, Mihai G Netea
Diabetes strongly predisposes to cardiovascular disease (CVD), the leading cause of mortality in these patients, as well as in the entire population. Hyperglycemia is an important cardiovascular risk factor as shown by the observation that even transient periods of hyperglycemia, despite return to normoglycemia during follow-up, increase the risk for CVD, a phenomenon termed 'hyperglycemic memory'. The molecular mechanisms underlying this phenomenon remain largely unknown. As inflammation plays an important role in the pathogenesis of atherosclerosis, we propose that long-term functional reprogramming of monocytes and macrophages, induced by hyperglycemia, plays an important role in the phenomenon of hyperglycemic memory leading to cardiovascular complications in patients with diabetes...
December 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27455328/therapeutic-targeting-of-telomerase
#19
REVIEW
Kathrin Jäger, Michael Walter
Telomere length and cell function can be preserved by the human reverse transcriptase telomerase (hTERT), which synthesizes the new telomeric DNA from a RNA template, but is normally restricted to cells needing a high proliferative capacity, such as stem cells. Consequently, telomerase-based therapies to elongate short telomeres are developed, some of which have successfully reached the stage I in clinical trials. Telomerase is also permissive for tumorigenesis and 90% of all malignant tumors use telomerase to obtain immortality...
2016: Genes
https://www.readbyqxmd.com/read/27367935/epigenetics-and-cardiovascular-risk-in-childhood
#20
Francesco Martino, Alessandra Magenta, Giuseppe Pannarale, Eliana Martino, Cristina Zanoni, Francesco M Perla, Paolo E Puddu, Francesco Barillà
Cardiovascular disease (CVD) can arise at the early stages of development and growth. Genetic and environmental factors may interact resulting in epigenetic modifications with abnormal phenotypic expression of genetic information without any change in the nucleotide sequence of DNA. Maternal dietary imbalance, inadequate to meet the nutritional needs of the fetus can lead to intrauterine growth retardation, decreased gestational age, low birth weight, excessive post-natal growth and metabolic alterations, with subsequent appearance of CVD risk factors...
August 2016: Journal of Cardiovascular Medicine
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