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histone deacetylase lipoprotein

Marie-Louise Ricketts, Bradley S Ferguson
BACKGROUND: Cardiovascular disease (CVD) is currently the leading cause of death globally. The metabolic syndrome (MetS), a clustering of risk factors including hypertension, hyperglycemia, elevated low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol and increased visceral adiposity, is a significant risk factor for the development of CVD. Non-alcoholic fatty liver disease (NAFLD), often referred to as the hepatic manifestation of MetS, is a constellation of progressive liver disorders closely linked to obesity, diabetes, and insulin resistance...
November 29, 2017: Current Pharmaceutical Design
Hai-Peng Cheng, Duo Gong, Zhen-Wang Zhao, Ping-Ping He, Xiao-Hua Yu, Qiong Ye, Chong Huang, Xin Zhang, Ling-Yan Chen, Wei Xie, Min Zhang, Liang Li, Xiao-Dan Xia, Xin-Ping Ouyang, Yu-Lin Tan, Zong-Bao Wang, Guo-Ping Tian, Xi-Long Zheng, Wei-Dong Yin, Chao-Ke Tang
BACKGROUND: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages...
August 29, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
Kenichi Takano, Takuya Kakuki, Yakuto Kaneko, Takayuki Kohno, Shin Kikuchi, Tetsuo Himi, Takashi Kojima
Tricellular tight junctions (tTJs) are specialized structures that occur where the corners of three cells meet to seal adjacent intercellular space. The molecular components of tTJs include tricellulin (TRIC) and lipolysis-stimulated lipoprotein receptor (LSR) which recruits TRIC, are required for normal hearing. Although loss of TRIC causes hearing loss with degeneration of cochlear cells, the detailed mechanisms remains unclear. In the present study, by using temperature-sensitive mouse cochlear cells, US/VOT-E36 cell line, we investigated the changes of TRIC and LSR during cochlear cell differentiation and the effects of histone deacetylase (HDAC) inhibitors against cell degeneration induced by loss of TRIC and LSR...
2017: PloS One
L J Reynolds, R I Pollack, R J Charnigo, C S Rashid, A J Stromberg, S Shen, J M O'Brien, K J Pearson
Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v...
May 9, 2017: Journal of Developmental Origins of Health and Disease
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...
February 15, 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
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