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histone deacetylase hypertension

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https://www.readbyqxmd.com/read/27816525/enhanced-nucleoplasmic-ca-2-signaling-in-ventricular-myocytes-from-young-hypertensive-rats
#1
Jelena Plačkić, Sebastian Preissl, Yulia Nikonova, Florentina Pluteanu, Lutz Hein, Jens Kockskämper
Arterial hypertension causes left ventricular (LV) myocyte hypertrophy. Alterations in nuclear Ca(2+) may be involved in regulation of histone acetylation, transcription and hypertrophy. Regulation of nuclear Ca(2+) in hypertension, however, is unknown. Therefore, we elucidated cellular mechanisms underlying nuclear Ca(2+) regulation in LV myocytes from hypertensive versus normotensive rats and evaluated possible consequences for Ca(2+)-dependent regulation of histone acetylation. LV myocytes and myocyte nuclei were isolated from young spontaneously hypertensive rats (SHR) shortly after development of hypertension...
November 3, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27754271/sy-17-1-dynamic-regulation-of-redox-regulating-factor-ape1-ref-1-on-the-oxidative-stress-and-vascular-inflammation
#2
Byeong Hwa Jeon
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that plays a central role in the cellular response to DNA damage and redox regulation against oxidative stress. APE1/Ref-1 is essential for cellular survival and embryonic lethal in knockout mouse models. Heterozygous APE1/Ref-1 mice showed impaired endothelium-dependent vasorelaxation, reduced vascular NO levels, and are hypertensive. APE1/Ref-1 reduces intracellular reactive oxygen species production by negatively regulating the activity of the NADPH oxidase...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27754177/sy-15-4-role-of-histone-deacetylases-in-regulating-endothelial-and-vascular-function
#3
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27754028/yia-03-04-epigenetic-changes-after-acute-treatment-with-acute-angiotensin-converting-enzyme-inhibitors-acei
#4
Nathan De Vries, Priscilla Prestes, Indrajeet Rana, Stephen B Harrap, Fadi J Charchar
OBJECTIVE: The 'legacy effect' of hypertension treatment is where short term treatment with blood pressure (BP) lowering drugs such as angiotensin converting enzyme inhibitors (ACEi) is followed by a persistent reduction in BP, reduced cardiovascular complications and increased lifespan. However, the involvement of epigenetics mechanisms remains unclear. DNA methylation is the binding of a methyl group to DNA which inhibits gene transcription. The aim of this study is to investigate DNA methylation changes after short term treatment with ACEi...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27673327/roles-of-hdac2-and-hdac8-in-cardiac-remodeling-in-renovascular-hypertensive-rats-and-the-effects-of-valproic-acid-sodium
#5
Rui-Fang Li, Shan-Shan Cao, Wei-Jin Fang, Ying Song, Xue-Ting Luo, Hong-Yun Wang, Jian-Gang Wang
Recent studies indicate that histone deacetylases (HDACs) activity is associated with the development and progression of cardiac hypertrophy. In this study, we investigated the effects of a HDACs inhibitor, valproic acid sodium (VPA), on cardiac remodeling and the differential expression of HDACs in left ventricles (LVs) of renovascular hypertensive rats. Renovascular hypertension was induced in rats by the two-kidney two-clip (2K2C) method. Cardiac remodeling, heart function and the differential expression of HDACs were examined at different weeks after 2K2C operation...
September 27, 2016: Pharmacology
https://www.readbyqxmd.com/read/27643268/sy-17-1-dynamic-regulation-of-redox-regulating-factor-ape1-ref-1-on-the-oxidative-stress-and-vascular-inflammation
#6
Byeong Hwa Jeon
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that plays a central role in the cellular response to DNA damage and redox regulation against oxidative stress. APE1/Ref-1 is essential for cellular survival and embryonic lethal in knockout mouse models. Heterozygous APE1/Ref-1 mice showed impaired endothelium-dependent vasorelaxation, reduced vascular NO levels, and are hypertensive. APE1/Ref-1 reduces intracellular reactive oxygen species production by negatively regulating the activity of the NADPH oxidase...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643134/sy-15-4-role-of-histone-deacetylases-in-regulating-endothelial-and-vascular-function
#7
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27642946/yia-03-04-epigenetic-changes-after-acute-treatment-with-acute-angiotensin-converting-enzyme-inhibitors-acei
#8
Nathan De Vries, Priscilla Prestes, Indrajeet Rana, Stephen B Harrap, Fadi J Charchar
OBJECTIVE: The 'legacy effect' of hypertension treatment is where short term treatment with blood pressure (BP) lowering drugs such as angiotensin converting enzyme inhibitors (ACEi) is followed by a persistent reduction in BP, reduced cardiovascular complications and increased lifespan. However, the involvement of epigenetics mechanisms remains unclear. DNA methylation is the binding of a methyl group to DNA which inhibits gene transcription. The aim of this study is to investigate DNA methylation changes after short term treatment with ACEi...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27620069/histone-deacetylase-inhibitors-future-therapeutics-for-insulin-resistance-and-type-2-diabetes
#9
Sorabh Sharma, Rajeev Taliyan
Insulin resistance is a common feature of obesity and predisposes the affected individuals to a variety of pathologies, including type 2 diabetes mellitus (T2DM), dyslipidemias, hypertension, cardiovascular disease etc. Insulin resistance is the primary cause of T2DM and it occurs many years before the disease onset. Although Thiazolidinediones (TZDs) such as rosiglitazone and pioglitazone are outstanding insulin sensitizers and are in clinical use since 1990s, however, their serious side effects such as heart attack and bladder cancer have limited their utilization...
September 9, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27610034/histone-deacetylase-inhibitor-cg200745-attenuates-cardiac-hypertrophy-and-fibrosis-in-doca-induced-hypertensive-rats
#10
Eunjo Lee, Min-Ji Song, Hae-Ahm Lee, Seol-Hee Kang, Mina Kim, Eun Kyoung Yang, Do Young Lee, Seonggu Ro, Joong Myung Cho, Inkyeom Kim
CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl...
September 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27539364/bromodomain-and-extra-terminal-protein-mimic-jq1-decreases-inflammation-in-human-vascular-endothelial-cells-implications-for-pulmonary-arterial-hypertension
#11
Sharon Mumby, Natalia Gambaryan, Chao Meng, Frederic Perros, Marc Humbert, S John Wort, Ian M Adcock
BACKGROUND AND OBJECTIVE: Nuclear factor kappa B (NF-kB)-mediated inflammatory gene expression and vascular endothelial cell proliferation/remodelling are implicated in the pathophysiology of the fatal disease, pulmonary arterial hypertension (PAH). Bromodomain and extra-terminal (BET) proteins are essential for the expression of a subset of NF-kB-induced inflammatory genes. BET mimics including JQ1+ prevent binding of BETs to acetylated histones and down-regulate the expression of selected genes...
August 18, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27512969/histone-deacetylase-and-gata-binding-factor-6-regulate-arterial-remodeling-in-angiotensin-ii-induced-hypertension
#12
Gwi Ran Kim, Soo-Na Cho, Hyung-Seok Kim, Seon Young Yu, Sin Young Choi, Yuhee Ryu, Ming Quan Lin, Li Jin, Hae Jin Kee, Myung Ho Jeong
OBJECTIVE: Histone deacetylase (HDAC) inhibitors have been reported to improve essential and secondary hypertension. However, the specific HDAC that might serve as a therapeutic target and the associated upstream and downstream molecules involved in regulating hypertension remain unknown. Our study was aimed at investigating whether a selective inhibitor of class II HDAC (MC1568) modulates hypertension, elucidating the underlying mechanism. METHODS: Hypertension was established by administering angiotensin II (Ang II) to mice before treatment with MC1568...
November 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27498117/inhibition-of-histone-deacetylase-reduces-transcription-of-nadph-oxidases-and-ros-production-and-ameliorates-pulmonary-arterial-hypertension
#13
Feng Chen, Xueyi Li, Emily Aquadro, Stephen Haigh, Jiliang Zhou, David W Stepp, Neal L Weintraub, Scott A Barman, David J R Fulton
Excessive levels of reactive oxygen species (ROS) and increased expression of NADPH oxidases (Nox) have been proposed to contribute to pulmonary artery hypertension (PAH) and other cardiovascular diseases (CVD). Nox enzymes are major sources of ROS but the mechanisms regulating changes in Nox expression in disease states remain poorly understood. Epigenetics encompasses a number of mechanisms that cells employ to regulate the ability to read and transcribe DNA. Histone acetylation is a prominent example of an epigenetic mechanism regulating the expression of numerous genes by altering chromatin accessibility...
October 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27403998/hdac-inhibitor-mediated-epigenetic-regulation-of-glaucoma-associated-tgf%C3%AE-2-in-the-trabecular-meshwork
#14
Jaclyn Y Bermudez, Hannah C Webber, Gaurang C Patel, Xiangyang Liu, Yi-Qiang Cheng, Abbot F Clark, Weiming Mao
PURPOSE: Elevated intraocular pressure (IOP) in primary open-angle glaucoma (POAG) results from glaucomatous damage to the trabecular meshwork (TM). The glaucoma-associated factor TGFβ2 is increased in aqueous humor and TM of POAG patients. We hypothesize that histone acetylation has a role in dysregulated TGFβ2 expression. METHODS: Protein acetylation was compared between nonglaucomatous TM (NTM) and glaucomatous TM (GTM) cells using Western immunoblotting (WB)...
July 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27362706/histone-deacetylase-inhibition-but-not-a-mineralocorticoid-receptor-antagonist-spironolactone-attenuates-atypical-transcription-by-an-activating-mutant-mr-mrs-810l
#15
Seol-Hee Kang, Hae-Ahm Lee, Eunjo Lee, Mina Kim, Inkyeom Kim
A mutation in the mineralocorticoid receptor (MRS 810L ) leads to early-onset hypertension, which is markedly exacerbated during pregnancy. The mutation causes progesterone and even the MR antagonist spironolactone to become potent agonists. Thus, it is hard to control hypertension in patients harbouring this mutation. We hypothesized that histone deacetylase inhibition (HDACi), but not the MR antagonist spironolactone, attenuates atypical transcriptional activity of activating mutant MR (MRS 810L ). We established HEK293T cells overexpressing wild-type MR (MRWT ) or MRS 810L and determined their transcriptional activities by luciferase assay...
October 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27324164/negative-autoregulation-of-bmp-dependent-transcription-by-sin3b-splicing-reveals-a-role-for-rbm39
#16
Noel Faherty, Matthew Benson, Eshita Sharma, Angela Lee, Alison Howarth, Helen Lockstone, Daniel Ebner, Shoumo Bhattacharya
BMP signalling is negatively autoregulated by several genes including SMAD6, Noggin and Gremlin, and autoregulators are possible targets for enhancing BMP signalling in disorders such as fibrosis and pulmonary hypertension. To identify novel negative regulators of BMP signalling, we used siRNA screening in mouse C2C12 cells with a BMP-responsive luciferase reporter. Knockdown of several splicing factors increased BMP4-dependent transcription and target gene expression. Knockdown of RBM39 produced the greatest enhancement in BMP activity...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27246590/epigenetic-mechanisms-in-pulmonary-arterial-hypertension-the-need-for-global-perspectives
#17
Prakash Chelladurai, Werner Seeger, Soni Savai Pullamsetti
Pulmonary arterial hypertension (PAH) is a severe and progressive disease, characterised by high pulmonary artery pressure that usually culminates in right heart failure. Recent findings of alterations in the DNA methylation state of superoxide dismutase 2 and granulysin gene loci; histone H1 levels; aberrant expression levels of histone deacetylases and bromodomain-containing protein 4; and dysregulated microRNA networks together suggest the involvement of epigenetics in PAH pathogenesis. Thus, PAH pathogenesis evidently involves the interplay of a predisposed genetic background, epigenetic state and injurious events...
June 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27106211/lysine-deacetylase-inhibition-attenuates-hypertension-and-is-accompanied-by-acetylation-of-mineralocorticoid-receptor-instead-of-histone-acetylation-in-spontaneously-hypertensive-rats
#18
Young Mi Seok, Hae Ahm Lee, Kwon Moo Park, Mi-Hyang Hwangbo, In Kyeom Kim
Inhibition of lysine deacetylase (KDAC) attenuated development of hypertension in spontaneously hypertensive rats (SHRs). We hypothesized that KDAC inhibition attenuates hypertension and is accompanied by acetylation of mineralocorticoid receptors (MR) instead of histone acetylation in SHRs. Valproate (VPA, 0.71 % wt/vol), an inhibitor of class I KDACs, was administered in drinking water to 7-week-old SHRs and Wistar Kyoto rats for 11 weeks. MR acetylation was determined by immunoprecipitation with anti-MR antibody followed by western blot with anti-acetyl-lysine antibody...
July 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27060376/ischemic-preconditioning-retinal-neuroprotection-and-histone-deacetylase-activities
#19
Jie Fan, Oday Alsarraf, C James Chou, Phillip W Yates, Nicole C Goodwin, Dennis S Rice, Craig E Crosson
Increased histone deacetylase (HDAC) activity and the resulting dysregulation of protein acetylation is an integral event in retinal degenerations associated with ischemia and ocular hypertension. This study investigates the role of preconditioning on the process of acetylation in ischemic retinal injury. Rat eyes were unilaterally subjected to retinal injury by 45 min of acute ischemia, and retinal neuroprotection induced by 5 min of an ischemic preconditioning (IPC) event. HDAC activity was evaluated by a fluorometric enzymatic assay with selective isoform inhibitors...
May 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/26836950/phase-ii-multicentre-trial-of-oral-quisinostat-a-histone-deacetylase-inhibitor-in-patients-with-previously-treated-stage-ib-iva-mycosis-fungoides-s%C3%A3-zary-syndrome
#20
F Child, P L Ortiz-Romero, R Alvarez, M Bagot, R Stadler, M Weichenthal, R Alves, P Quaglino, M Beylot-Barry, R Cowan, L J Geskin, A Pérez-Ferriols, P Hellemans, Y Elsayed, C Phelps, A Forslund, M Kamida, P L Zinzani
BACKGROUND: Quisinostat is a hydroxamate, second-generation, orally available pan-histone deacetylase inhibitor. OBJECTIVES: To evaluate the efficacy and safety of oral quisinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL). METHODS: Patients received quisinostat 8 mg or 12 mg on days 1, 3 and 5 of each week in 21-day treatment cycles. Primary efficacy end point was cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT)...
July 2016: British Journal of Dermatology
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