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histone deacetylase atherosclerosis

Qingguo Zhao, Shuqiang Li, Nan Li, Xiaoling Yang, Shengchao Ma, Anning Yang, Hui Zhang, Songhao Yang, Caiyan Mao, Lingbo Xu, Tingting Gao, Xiaoming Yang, Huiping Zhang, Yideng Jiang
Hyperhomocysteinemia (HHcy) promotes atherogenesis by modification of histone acetylation patterns and regulation of miRNA expression while the underlying molecular mechanisms are not well known. In this study, we investigated the effects of homocysteine (Hcy) on the expression of histone deacetylase 1 (HDAC1) and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased HDAC1 expression, which is regulated by miR-34a. The expression of HDAC1 increased and acetylation of histone H3 at lysine 9 (H3K9ac) decreased in the aorta of ApoE(-/-) mice fed with high methionine diet, whereas miR-34a expression was inhibited...
May 9, 2017: Journal of Cellular Biochemistry
Liam J Ward, Stefan A Ljunggren, Helen Karlsson, Wei Li, Xi-Ming Yuan
The 7-oxysterols are recognised as strong enhancers of inflammatory processes in foamy macrophages. Atheroma-relevant 7-oxysterol mixtures induce a mixed type of cell death in macrophages, and trigger cellular oxidative stress responses, which mimic oxidative exposures observed in atherosclerotic lesions. However, the macrophage proteome has not previously been determined in the 7-oxysterol treated cell model. The aim of the present study was to determine the specific effects of an atheroma-relevant 7-oxysterol mixture on human macrophage proteome...
2017: PloS One
Rainer Malik, Therese Dau, Maria Gonik, Anirudh Sivakumar, Daniel J Deredge, Evgeniia V Edeleva, Jessica Götzfried, Sander W van der Laan, Gerard Pasterkamp, Nathalie Beaufort, Susana Seixas, Steve Bevan, Lisa F Lincz, Elizabeth G Holliday, Annette I Burgess, Kristiina Rannikmäe, Jens Minnerup, Jennifer Kriebel, Melanie Waldenberger, Martina Müller-Nurasyid, Peter Lichtner, Danish Saleheen, Peter M Rothwell, Christopher Levi, John Attia, Cathie L M Sudlow, Dieter Braun, Hugh S Markus, Patrick L Wintrode, Klaus Berger, Dieter E Jenne, Martin Dichgans
Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3'-UTR (rs2023938; P = 7...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
Thorsten M Leucker, Yohei Nomura, Jae Hyung Kim, Anil Bhatta, Victor Wang, Andrea Wecker, Sandeep Jandu, Lakshmi Santhanam, Dan Berkowitz, Lewis Romer, Deepesh Pandey
Endothelial cystathionine γ-lyase (CSEγ) contributes to cardiovascular homeostasis, mainly through production of H2S. However, the molecular mechanisms that control CSEγ gene expression in the endothelium during cardiovascular diseases are unclear. The aim of the current study is to determine the role of specific histone deacetylases (HDACs) in the regulation of endothelial CSEγ. Reduced CSEγ mRNA expression and protein abundance were observed in human aortic endothelial cells (HAEC) exposed to oxidized LDL (OxLDL) and in aortas from atherogenic apolipoprotein E knockout (ApoE(-/-)) mice fed a high-fat diet compared with controls...
April 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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
Feng Liu, Ming Zong, Xiaofei Wen, Xuezhu Li, Jun Wang, Yi Wang, Wei Jiang, Xiaojun Li, Zhongliang Guo, Hualin Qi
Podocyte dysfunction is important in the onset and development of diabetic nephropathy (DN). Histone deacetylases (HDACs) have been recently proved to play critical roles in the pathogenesis of DN. As one subtype of the class IIa HDACs, HDAC9 is capable to repress/de-repress their target genes in tumor, inflammation, atherosclerosis and metabolic diseases. In the present study, we investigate whether HDAC9 is involved in the pathophysiologic process of DN, especially the podocyte injury. Firstly, we explored the expression patterns and localization of HDAC9 and found that HDAC9 expression was significantly up-regulated in high glucose (HG)-treated mouse podocytes, as well as kidney tissues from diabetic db/db mice and patients with DN...
September 16, 2016: Scientific Reports
Xue-Bin Wang, Ya-di Han, Shrestha Sabina, Ning-Hua Cui, Shuai Zhang, Ze-Jin Liu, Cong Li, Fang Zheng
A previous genome-wide association study showed that a single nucleotide polymorphism (SNP) rs2107595 in histone deacetylase 9 (HDAC9) gene was associated with large artery stroke (LAS) in Caucasians. Based on the similar atherosclerotic pathogenesis between LAS and coronary artery disease (CAD), we aimed to evaluate the associations of SNP rs2107595 with CAD risk and the severity of coronary atherosclerosis in a Chinese Han population, and explore the potential gene-environment interactions among SNP rs2107595 and conventional CAD risk factors...
2016: PloS One
Junya Makino, Rie Ogasawara, Tetsuro Kamiya, Hirokazu Hara, Yukari Mitsugi, Eiji Yamaguchi, Akichika Itoh, Tetsuo Adachi
Extracellular superoxide dismutase (EC-SOD) is one of the main SOD isozymes and plays an important role in the prevention of cardiovascular diseases by accelerating the dismutation reaction of superoxide. Royal jelly includes 10-hydroxy-2-decenoic acid (10H2DA, 2), which regulates the expression of various types of genes in epigenetics through the effects of histone deacetylase (HDAC) antagonism. The expression of EC-SOD was previously reported to be regulated epigenetically through histone acetylation in THP-1 cells...
April 22, 2016: Journal of Natural Products
Zhu-Qin Zhang, Si-Chong Ren, Ying Tan, Zuo-Zhi Li, Xiaoqiang Tang, Ting-Ting Wang, De-Long Hao, Xiang Zhao, Hou-Zao Chen, De-Pei Liu
Sirt6 is a member of the class III histone deacetylase family which is associated with aging and longevity. Sirt6 deficient mice show an aging-like phenotype, while male transgenic mice of Sirt6 show increased longevity. Sirt6 acts as a tumor suppressor and deficiency of Sirt6 leads to cardiac hypertrophy and heart failure. Whether Sirt6 is involved in atherosclerosis development, the major cause of cardiovascular diseases, is unknown. We found that the expression of Sirt6 is lower in human atherosclerotic plaques than that in controls...
April 5, 2016: Scientific Reports
I S Stafeev, M Y Menshikov, Z I Tsokolaeva, M V Shestakova, Ye V Parfyonova
The problem of metabolic syndrome is one of the most important in medicine today. The main hazard of metabolic syndrome is development of latent inflammation in adipose tissue, which promotes atherosclerosis, non-alcoholic fatty liver disease, myocarditis, and a number of other illnesses. Therefore, understanding of molecular mechanisms of latent inflammation in adipose tissue is very important for treatment of metabolic syndrome. Three main components that arise during hypertrophy and hyperplasia of adipocytes underlie such inflammation: endoplasmic reticulum stress, oxidative stress, and hypoxia...
October 2015: Biochemistry. Biokhimii︠a︡
Guo Qingxu, Zhang Yan, Xu Jiannan, Liu Yunlong
Genome-wide association studies have demonstrated various polymorphisms of histone deacetylase 9 (HDAC9) gene was strong risk locus for large-vessel stroke, but the results were controversial. This study aims to replicate the association between the previous detected SNPs of HDAC9 and the susceptibility of ischemic stroke. The study population consisted of 262 consecutive patients diagnosed with ischemic stroke and 300 age and gender matched unrelated controls between October 2012 and October 2014. Rs11984041, rs2389995, and rs2240419 of HDAC9 were genotyped and compared between the cases and controls...
January 2016: Pathology Oncology Research: POR
XiaoLe Xu, Mengzi He, Tingting Liu, Yi Zeng, Wei Zhang
BACKGROUND/AIMS: salusin-β is considered to be a potential pro-atherosclerotic factor. Regulation and function of vascular smooth muscle cells (VSMCs) are important in the progression of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ) exerts a vascular protective role beyond its metabolic effects. Salusin-β has direct effects on VSMCs. The aim of the present study was to assess the effect of salusin-β on PPARγ gene expression in primary cultured rat VSMCs...
2015: Cellular Physiology and Biochemistry
Annette E Neele, Jan Van den Bossche, Marten A Hoeksema, Menno P J de Winther
Atherosclerosis is a lipid-driven chronic inflammatory disorder. Monocytes and macrophages are key immune cells in the development of disease and clinical outcome. It is becoming increasingly clear that epigenetic pathways govern many aspects of monocyte and macrophage differentiation and activation. The dynamic regulation of epigenetic patterns provides opportunities to alter disease-associated epigenetic states. Therefore, pharmaceutical companies have embraced the targeting of epigenetic processes as new approaches for interventions...
September 15, 2015: European Journal of Pharmacology
Xia-xia Zheng, Tian Zhou, Xin-An Wang, Xiao-hong Tong, Jia-wang Ding
Atherosclerosis is the most common pathological process that leads to cardiovascular diseases, a disease of large- and medium-sized arteries that is characterized by a formation of atherosclerotic plaques consisting of necrotic cores, calcified regions, accumulated modified lipids, smooth muscle cells (SMCs), endothelial cells, leukocytes, and foam cells. Recently, the question about how to suppress the occurrence of atherosclerosis and alleviate the progress of cardiovascular disease becomes the hot topic...
June 2015: Atherosclerosis
Anne Sofie Høgh Kølbæk Kjær, Christel Rothe Brinkmann, Charles A Dinarello, Rikke Olesen, Lars Østergaard, Ole Schmeltz Søgaard, Martin Tolstrup, Thomas Aagaard Rasmussen
OBJECTIVE: To investigate the effect of the histone deacetylase inhibitor panobinostat on HIV-associated inflammation. DESIGN: Sub-study of a single-arm, phase I/II clinical trial. METHODS: HIV-infected adults on suppressive antiretroviral therapy received oral panobinostat 20 mg three times per week, every other week, for 8 weeks, that is, four cycles of treatment. Plasma levels of high-sensitivity C-reactive protein, matrix metalloproteinase 9, soluble CD40 ligand and interleukin-6 were determined using human ELISA kits...
June 19, 2015: AIDS
Chiara Cencioni, Francesco Spallotta, Antonello Mai, Fabio Martelli, Antonella Farsetti, Andreas M Zeiher, Carlo Gaetano
Age is the most important risk factor for metabolic alterations and cardiovascular accidents. Although class III histone deacetylases, alias Sirtuins, have been appealed as "the fountain of youth" their role in longevity control and prevention of aging-associated disease is still under debate. Indeed, several lines of evidence indicate that sirtuin activity is strictly linked to metabolism and dependent on NAD(+) synthesis both often altered as aging progresses. During aging the cardiovascular system is attacked by a variety of environmental stresses, including those determined by high blood glucose and lipid levels, or by the presence of oxidized lipoproteins which, among others, determine important oxidative stress signals...
June 2015: Journal of Molecular and Cellular Cardiology
Jan Van den Bossche, Annette E Neele, Marten A Hoeksema, Femke de Heij, Marieke C S Boshuizen, Saskia van der Velden, Vincent C de Boer, Kris A Reedquist, Menno P J de Winther
Macrophages determine the outcome of atherosclerosis by propagating inflammatory responses, foam cell formation and eventually necrotic core development. Yet, the pathways that regulate their atherogenic functions remain ill-defined. It is now apparent that chromatin remodeling chromatin modifying enzymes (CME) governs immune responses but it remains unclear to what extent they control atherogenic macrophage functions. We hypothesized that epigenetic mechanisms regulate atherogenic macrophage functions, thereby determining the outcome of atherosclerosis...
December 12, 2014: Biochemical and Biophysical Research Communications
Y Cao, L Lu, M Liu, X-C Li, R-R Sun, Y Zheng, P-Y Zhang
Cardiovascular disease (CVD) is the leading cause of death, irrespective of socioeconomic status, ethnic background and sex. Despite the considerable progress in the treatment, the complex pathophysiology underlying CVD is still not clear. In past few years, genetic approaches including epigenetics and personalized medicine initiated a new way of treating CVD. Epigenetics refers to the non-DNA sequence related heritable changes in gene expression and its role in understanding and treating coronary artery disease, heart failure, and cardiac hypertrophy is currently recognized as an important player...
October 2014: European Review for Medical and Pharmacological Sciences
Omana P Mathew, Kasturi Ranganna, Shirlette G Milton
Epigenetic mechanisms by altering the expression and, in turn, functions of target genes have potential to modify cellular processes that are characteristics of atherosclerosis, including inflammation, proliferation, migration and apoptosis/cell death. Butyrate, a natural epigenetic modifier and a histone deacetylase inhibitor (HDACi), is an inhibitor of vascular smooth muscle cell (VSMC) proliferation, a critical event in atherogenesis. Here, we examined whether glutathione peroxidases (GPxs), a family of antioxidant enzymes, are modulated by butyrate, contributing to its antiproliferation action on VSMC through the regulation of the inflammatory response by using western blotting, immunostaining methods and activity assay...
2014: Pharmaceuticals
Sepiede Azghandi, Caroline Prell, Sander W van der Laan, Manuela Schneider, Rainer Malik, Kerstin Berer, Norbert Gerdes, Gerard Pasterkamp, Christian Weber, Christof Haffner, Martin Dichgans
BACKGROUND AND PURPOSE: Recent genome-wide association studies identified the histone deacetylase 9 (HDAC9) gene region as a major risk locus for large-vessel stroke and coronary artery disease. However, the mechanisms linking variants at this locus to vascular risk are poorly understood. In this study, we investigated the candidacy and directionality of HDAC9 in atherosclerosis and analyzed associations between risk alleles at 7p21.1 and plaque characteristics. METHODS: Allele-dependent expression of HDAC9 was analyzed in human peripheral blood mononuclear cells of healthy donors...
January 2015: Stroke; a Journal of Cerebral Circulation
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