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histone deacetylase lipoprotein

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
Nethrie D Idippily, Chunfang Gan, Paul Orefice, Jane Peterson, Bin Su
Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
Ye Bai, Shaohui Du, Fei Li, Fengyuan Huang, Rudong Deng, Jianhong Zhou, Dongfeng Chen
Hypaconitine is an active component of Aconitum carmichaelii Debx, a Chinese medicinal herb for the treatment of cardiovascular diseases, but the mechanism underlying its effect remains elusive. In this study, we found that hypaconitine, rather than aconitum alkaloids in A. carmichaelii (e.g. aconitine, mesaconitine and benzoylaconitine), prevented endothelial cells from damage due to oxidized low-density lipoprotein (oxLDL) challenge. Cleaved caspase 3 expression in endothelial cells was up-regulated by oxLDL and markedly attenuated by hypaconitine, suggesting that hypaconitine inhibited the oxLDL-induced cell apoptosis...
March 2017: Experimental Biology and Medicine
Fan Yang, Yu Du, Jin Zhang, Zhibo Jiang, Li Wang, Bin Hong
Scavenger receptor class B type I (SR-BI) is one of the key proteins in the process of reverse cholesterol transport (RCT), and its major function is to uptake high density lipoprotein (HDL) cholesterol from plasma into liver cells. The regulation of SR-BI expression is important for controlling serum lipid content and reducing the risks of cardiovascular diseases. Here we found that SR-BI expression was significantly increased by LDL in vivo and in vitro, and the transcription factor specific protein 1 (Sp1) plays a critical role in this process...
September 2016: Biochimica et Biophysica Acta
Abhik Sen, Thomas J Nelson, Daniel L Alkon
Apolipoprotein E4 (ApoE4) is a major genetic risk factor for several neurodegenerative disorders, including Alzheimer's disease (AD). Epigenetic dysregulation, including aberrations in histone acetylation, is also associated with AD. We show here for the first time that ApoE4 increases nuclear translocation of histone deacetylases (HDACs) in human neurons, thereby reducing BDNF expression, whereas ApoE3 increases histone 3 acetylation and upregulates BDNF expression. Amyloid-β (Aβ) oligomers, which have been implicated in AD, caused effects similar to ApoE4...
May 13, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Changjun Li, Weishan Wang, Liang Xie, Xianghang Luo, Xu Cao, Mei Wan
Parathyroid hormone (PTH) suppresses the expression of the bone formation inhibitor sclerostin (Sost) in osteocytes by inducing nuclear accumulation of histone deacetylases (HDACs) to inhibit the myocyte enhancer factor 2 (MEF2)-dependent Sost bone enhancer. Previous studies revealed that lipoprotein receptor-related protein 6 (LRP6) mediates the intracellular signaling activation and the anabolic bone effect of PTH. Here, we investigated whether LRP6 mediates the inhibitory effect of PTH on Sost using an osteoblast-specific Lrp6-knockout (LRP6-KO) mouse model...
January 2016: Annals of the New York Academy of Sciences
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
Sorabh Sharma, Rajeev Taliyan, Shruti Ramagiri
Metabolic syndrome is increasingly recognized for its effects on cognitive health. Recent studies have highlighted the role of histone deacetylases (HDACs) in metabolic syndrome and cognitive functions. The present study was designed to investigate the possible therapeutic role of a HDAC inhibitor, trichostatin A (TSA), in cognitive impairment associated with metabolic syndrome. To ascertain the mechanisms involved, we fed mice with high-fat diet (HFD) for 4 weeks and examined changes in behavioral and biochemical/oxidative stress markers...
May 2015: Journal of Molecular Neuroscience: MN
Qiang Cao, Shunxing Rong, Joyce J Repa, Richard St Clair, John S Parks, Nilamadhab Mishra
OBJECTIVE: Recent genome-wide association studies revealed that a genetic variant in the loci corresponding to histone deacetylase 9 (HDAC9) is associated with large vessel stroke. HDAC9 expression was upregulated in human atherosclerotic plaques in different arteries. The molecular mechanisms how HDAC9 might increase atherosclerosis is not clear. APPROACH AND RESULTS: In this study, we show that systemic and bone marrow cell deletion of HDAC9 decreased atherosclerosis in LDLr(-/-) (low density lipoprotein receptor) mice with minimal effect on plasma lipid concentrations...
September 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
Deepesh Pandey, Gautam Sikka, Yehudit Bergman, Jae Hyung Kim, Sungwoo Ryoo, Lewis Romer, Dan Berkowitz
OBJECTIVE: Arginase 2 (Arg2) is a critical target in atherosclerosis because it controls endothelial nitric oxide, proliferation, fibrosis, and inflammation. Regulators of Arg2 transcription in the endothelium have not been characterized. The goal of the current study is to determine the role of specific histone deacetylases (HDACs) in the regulation of endothelial Arg2 transcription and endothelial function. APPROACH AND RESULTS: The HDAC inhibitor trichostatin A increased levels of Arg2 mRNA, protein, and activity in both human aortic endothelial cells and mouse aortic rings...
July 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
Rongya Tao, Xiwen Xiong, Ronald A DePinho, Chu-Xia Deng, X Charlie Dong
Elevated LDL-cholesterol is a risk factor for the development of cardiovascular disease. Thus, proper control of LDL-cholesterol homeostasis is critical for organismal health. Genetic analysis has identified PCSK9 (proprotein convertase subtilisin/kexin type 9) as a crucial gene in the regulation of LDL-cholesterol via control of LDL receptor degradation. Although biochemical characteristics and clinical implications of PCSK9 have been extensively investigated, epigenetic regulation of this gene is largely unknown...
October 11, 2013: Journal of Biological Chemistry
Tarak Nath Khatua, Ramu Adela, Sanjay K Banerjee
Garlic is widely recognized for its immense therapeutic potential. Garlic has been shown to exert its beneficial effects against a wide spectrum of diseases, including cancer, diabetes, and microbial infections, as well as immunological and cardiovascular disorders. Most of the research on garlic has indicated that garlic and its active compounds are effective in reducing cardiovascular and metabolic risk by normalizing abnormal plasma lipids, oxidized low density lipoproteins, abnormal platelet aggregation, high blood pressure, and cardiac injury...
June 2013: Canadian Journal of Physiology and Pharmacology
Zhuang Wu, Ming-Cheh Liu, Mei Liang, Jian Fu
Exposure to ambient particulate matter (PM) air pollution has been reported to trigger inflammation and thrombosis. However, molecular mechanisms underlying the modulation of coagulation pathways in PM-induced thrombosis remain largely unknown. We report here that Sirt1, a member of class III histone deacetylase, controls lung inflammation and coagulation after PM exposure. Sirt1 knock-out mice exhibited aggravated lung vascular leakage and inflammation after PM exposure, which was correlated with increased NF-κB acetylation and activation...
March 8, 2012: Blood
Ku-Chung Chen, Yi-Chu Liao, I-Chung Hsieh, Yung-Song Wang, Ching-Yu Hu, Suh-Hang Hank Juo
MicroRNA-29b has been reported to epigenetically regulate proatherogenic genes in response to oxLDL. Since transcription factors and epigenetic regulations are important mechanisms to regulate gene expression, we investigated whether these mechanisms are involved in oxLDL-induced microRNA-29b upregulation. First, we confirmed that microRNA-29b expression was increased in the aorta of mice fed with a high-fat diet, which was consistent with our previous in vitro findings. Next, we found that oxLDL only activated the microRNA-29b-1/microRNA-29a cluster gene on chromosome 7 but not the other distinct microRNA-29b gene located on chromosome 1...
March 2012: Journal of Molecular and Cellular Cardiology
Chai Siah Ku, Youngki Park, Sara L Coleman, Jiyoung Lee
Reverse cholesterol transport (RCT), a process to deliver excess cholesterol from the periphery to the liver for excretion from body, is a major atheroprotective property of high-density lipoproteins. As major transporters for cholesterol efflux in macrophages, ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) are critical for RCT. We investigated mechanisms for the regulation of ABCA1 and ABCG1 expression by fatty acids (FA) in RAW264.7 macrophages. Cells were incubated with 100 μmol/L of palmitic, oleic, linoleic, linolenic or eicosapentaenoic acids in the absence or presence of T0901317, a liver X receptor (LXR) agonist...
October 2012: Journal of Nutritional Biochemistry
Xiaofang Chen, Li Wang, Yu Du, Yanbin Wu, Xiaojian Jia, Yuan Yang, Bin Hong
Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) were reported in our recent publication as novel human high density lipoprotein (HDL) receptor CD36 and Lysosomal integral membrane protein-II Analogous-1 (CLA-1) up-regulators. As part of a broader effort to more fully explore the structure-activity relationships (SAR) of CLA-1 up-regulators, we synthesized a series of hydroxamic acid derivatives and evaluated their CLA-1 up-regulating activities in HepG2 cells. Some compounds exhibited over 10-fold up-regulation of CLA-1 expression in HepG2 cells at 10 μg/mL concentration...
2011: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yang Xu, Yanni Xu, Yi Bao, Bin Hong, Shuyi Si
The ATP-binding cassette transporter A1 (ABCA1) mediates the cellular efflux of excess cholesterol and phospholipids to lipid-poor apolipoprotein A-I (apoA-I). ABCA1 plays an important role in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. By using a cell-based screening model for the ABCA1 up-regulator and column chromatography, an active compound, 9179B, was isolated. Through analysis of its NMR data, 9179B was identified as dehydroxytrichostatin A. We found that 9179B increased the transcription of ABCA1 in a cell-based reporter assay, with an EC(50) value of 2...
2011: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Peter Langfelder, Lawrence W Castellani, Zhiqiang Zhou, Eric Paul, Richard Davis, Eric E Schadt, Aldons J Lusis, Steve Horvath, Margarete Mehrabian
We report a systems genetic analysis of high density lipoprotein (HDL) levels in an F2 intercross between inbred strains CAST/EiJ and C57BL/6J. We previously showed that there are dramatic differences in HDL metabolism in a cross between these strains, and we now report co-expression network analysis of HDL that integrates global expression data from liver and adipose with relevant metabolic traits. Using data from a total of 293 F2 intercross mice, we constructed weighted gene co-expression networks and identified modules (subnetworks) associated with HDL and clinical traits...
March 2012: Biochimica et Biophysica Acta
Sokrates Stein, Christian M Matter
SIRT1 is a NAD (+) -dependent class III histone deacetylase (HDAC) that mediates the effects of caloric restriction on lifespan and metabolic pathways in various organisms. It deacetylates both histone and non-histone proteins, and targets proteins with diverse cellular and tissue functions. In the vasculature of rodent models SIRT1 mediates vasodilatation via eNOS-derived nitric oxide (NO) and scavenging reactive oxygen species (ROS). Recent studies demonstrated further protective roles of SIRT1 in vascular biology and atherosclerosis...
February 15, 2011: Cell Cycle
Sokrates Stein, Christine Lohmann, Christoph Handschin, Elin Stenfeldt, Jan Borén, Thomas F Lüscher, Christian M Matter
BACKGROUND: Atherosclerosis is a chronic inflammatory disease that evolves from the interaction of activated endothelial cells, macrophages, lymphocytes and modified lipoproteins (LDLs). In the last years many molecules with crucial metabolic functions have been shown to prevent important steps in the progression of atherogenesis, including peroxisome proliferator activated receptors (PPARs) and the class III histone deacetylase (HDAC) SIRT1. The PPARγ coactivator 1 alpha (Ppargc1a or PGC-1α) was identified as an important transcriptional cofactor of PPARγ and is activated by SIRT1...
October 22, 2010: PloS One
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