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https://www.readbyqxmd.com/read/27913583/epigenetic-control-of-microsomal-prostaglandin-e-synthase-1-by-hdac-mediated-recruitment-of-p300
#1
Christian Fork, Andrea E Vasconez, Patrick Janetzko, Carlo Angioni, Yannick Schreiber, Nerea Ferreiros, Gerd Geisslinger, Matthias S Leisegang, Dieter Steinhilber, Ralf P Brandes
: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medicine to treat pain, fever, inflammation and to inhibit platelet function. Understanding the expression regulation of enzymes of the prostanoid pathway is of great medical relevance. Histone acetylation crucially controls gene expression. We set out to identify the impact of histone deacetylases (HDACs) on the generation of prostanoids and examine the consequences on vascular function. Inhibition of HDACs (HDACi) with the pan HDAC inhibitor SAHA attenuated prostaglandin E2 (PGE2) generation in the murine vasculature and in human vascular smooth muscle cells...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27904046/cocl2-decreases-ec-sod-expression-through-histone-deacetylation-in-cos7-cells
#2
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/27901321/copy-number-variants-in-a-population-based-investigation-of-klippel-trenaunay-syndrome
#3
Aggeliki Dimopoulos, Robert J Sicko, Denise M Kay, Shannon L Rigler, Ruzong Fan, Paul A Romitti, Marilyn L Browne, Charlotte M Druschel, Michele Caggana, Lawrence C Brody, James L Mills
Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder that is thought to occur sporadically; however, reports of familial occurrence suggest a genetic component. We examined KTS cases to identify novel, potentially causal copy number variants (CNVs). We identified 17 KTS cases from all live-births occurring in New York (1998-2010). Extracted DNA was genotyped using Illumina microarrays and CNVs were called using PennCNV software. CNVs selected for follow-up had ≥10 single nucleotide polymorphisms (SNPs) and minimal overlap with in-house controls or controls from the Database of Genomic Variants...
November 30, 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27898394/mef2-transcription-factors-are-key-regulators-of-sprouting-angiogenesis
#4
Natalia Sacilotto, Kira M Chouliaras, Leonid L Nikitenko, Yao Wei Lu, Martin Fritzsche, Marsha D Wallace, Svanhild Nornes, Fernando García-Moreno, Sophie Payne, Esther Bridges, Ke Liu, Daniel Biggs, Indrika Ratnayaka, Shane P Herbert, Zoltán Molnár, Adrian L Harris, Benjamin Davies, Gareth L Bond, George Bou-Gharios, John J Schwarz, Sarah De Val
Angiogenesis, the fundamental process by which new blood vessels form from existing ones, depends on precise spatial and temporal gene expression within specific compartments of the endothelium. However, the molecular links between proangiogenic signals and downstream gene expression remain unclear. During sprouting angiogenesis, the specification of endothelial cells into the tip cells that lead new blood vessel sprouts is coordinated by vascular endothelial growth factor A (VEGFA) and Delta-like ligand 4 (Dll4)/Notch signaling and requires high levels of Notch ligand DLL4...
October 15, 2016: Genes & Development
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
#5
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
#6
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/27706906/valproic-acid-selectively-increases-vascular-endothelial-tissue-type-plasminogen-activator-production-and-reduces-thrombus-formation-in-the-mouse
#7
P Larsson, I Alwis, B Niego, M Sashindranath, P Fogelstrand, M C L Wu, L Glise, M Magnusson, M Daglas, N Bergh, S P Jackson, R L Medcalf, S Jern
BACKGROUND: The endogenous fibrinolytic system has rarely been considered as a target to prevent thrombotic disease. Tissue plasminogen activator (t-PA) is potently increased by histone deacetylase (HDAC) inhibitors in endothelial cells in vitro, but whether this translates into increased vascular t-PA production and an enhanced fibrinolytic capacity in vivo is unknown. OBJECTIVES: The aim of this study was to determine if the HDAC inhibitor valproic acid (VPA) stimulates production of t-PA in the vasculature of mice, and further, if VPA pre-treatment affects fibrin deposition and clot formation after mechanical vessel injury...
October 5, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27669993/flow-induced-hdac1-phosphorylation-and-nuclear-export-in-angiogenic-sprouting
#8
Despina Bazou, Mei Rosa Ng, Jonathan W Song, Shan Min Chin, Nir Maimon, Lance L Munn
Angiogenesis requires the coordinated growth and migration of endothelial cells (ECs), with each EC residing in the vessel wall integrating local signals to determine whether to remain quiescent or undergo morphogenesis. These signals include vascular endothelial growth factor (VEGF) and flow-induced mechanical stimuli such as interstitial flow, which are both elevated in the tumor microenvironment. However, it is not clear how VEGF signaling and mechanobiological activation due to interstitial flow cooperate during angiogenesis...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27650558/age-associated-sirtuin-1-reduction-in-vascular-smooth-muscle-links-vascular-senescence-and-inflammation-to-abdominal-aortic-aneurysm
#9
Hou-Zao Chen, Fang Wang, Peng Gao, Jian-Fei Pei, Yue Liu, Ting-Ting Xu, Xiaoqiang Tang, Wen-Yan Fu, Jie Lu, Yun-Fei Yan, Xiao-Man Wang, Lei Han, Zhu-Qin Zhang, Ran Zhang, Ming-Hui Zou, De-Pei Liu
RATIONALE: Uncontrolled growth of abdominal aortic aneurysms (AAAs) is a life-threatening vascular disease without an effective pharmaceutical treatment. AAA incidence dramatically increases with advancing age in men. However, the molecular mechanisms by which aging predisposes individuals to AAAs remain unknown. OBJECTIVE: In this study, we investigated the role of SIRT1 (Sirtuin 1), a class III histone deacetylase, in AAA formation and the underlying mechanisms linking vascular senescence and inflammation...
October 28, 2016: Circulation Research
https://www.readbyqxmd.com/read/27649243/antioxidant-rich-extract-from-plantaginis-semen-ameliorates-diabetic-retinal-injury-in-a-streptozotocin-induced-diabetic-rat-model
#10
Thing-Fong Tzeng, Wayne Young Liu, Shorong-Shii Liou, Tang-Yao Hong, I-Min Liu
Plantaginis semen, the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd. (Plantaginaceae), has been traditionally used to treat blurred vision in Asia. The aim of this work was to investigate the effect of plantaginis semen ethanol extract (PSEE) on the amelioration of diabetic retinopathy (DR) in streptozotocin (STZ)-diabetic rats. PSEE has abundant polyphenols with strong antioxidant activity. PSEE (100, 200 or 300 mg/kg) was oral administrated to the diabetic rats once daily consecutively for 8 weeks...
2016: Nutrients
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
#11
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
#12
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/27635950/connectivity-map-identifies-hdac-inhibition-as-a-treatment-option-of-high-risk-hepatoblastoma
#13
Alexander Beck, Corinna Eberherr, Michaela Hagemann, Stefano Cairo, Beate Häberle, Christian Vokuhl, Dietrich von Schweinitz, Roland Kappler
Hepatoblastoma (HB) is the most common liver tumor of childhood, usually occurring in children under the age of 3 y. The prognosis of patients presenting with distant metastasis, vascular invasion and advanced tumor stages remains poor and children that do survive often face severe late effects from the aggressive chemotherapy regimen. To identify potential new therapeutics for high risk HB we used a 1,000-gene expression signature as input for a Connectivity Map (CMap) analysis, which predicted histone deacetylase (HDAC) inhibitors as a promising therapy option...
September 16, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27617745/histone-deacetylase-inhibition-restores-retinal-pigment-epithelium-function-in-hyperglycemia
#14
Danielle Desjardins, Yueying Liu, Craig E Crosson, Zsolt Ablonczy
In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells...
2016: PloS One
https://www.readbyqxmd.com/read/27610034/histone-deacetylase-inhibitor-cg200745-attenuates-cardiac-hypertrophy-and-fibrosis-in-doca-induced-hypertensive-rats
#15
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/27578018/p66-shc-sirt1-regulation-of-oxidative-stress-protects-against-cardio-cerebral-vascular-disease
#16
Xiangyi Kong, Jian Guan, Jun Li, Junji Wei, Renzhi Wang
Growing evidence shows that acute and chronic overproduction of reactive oxygen species (ROS) and increased oxidants under pathophysiologic circumstances are of vital importance in the development of cardio-cerebral vascular diseases (CCVDs). It has been revealed that the impact of ROS can be suppressed by sirtuin 1 (SIRT1), a member of the highly conserved nicotinamide adenine dinucleotide-dependent class III histone deacetylases through protecting endothelial cells from oxidative injury. Plenty of evidences indicate that p66Shc stimulates mitochondrial ROS generation through its oxidoreductase activity and plays a vital role in the pathophysiology of CCVDs...
August 30, 2016: Molecular Neurobiology
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
#17
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
#18
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/27510016/comparison-of-expression-signature-of-histone-deacetylases-hdacs-in-mesenchymal-stem-cells-from-multiple-myeloma-and-normal-donors
#19
Mohammad Ahmadvand, Mehrdad Noruzinia, Masoud Soleimani, Saeid Abroun
BACKGROUND: Histone acetylation in chromatin structures plays a key role in regulation of gene transcription and is strictly controlled by histone acetyltransferase (HAT) and deacetylase (HDAC) activities. HDAC deregulation has been reported in several cancers. MATERIALS AND METHODS: The expression of 10 HDACs (including HDAC class I and II) was studied by quantitative reverse transcriptionPCR (qRTPCR) in a cohort of mesenchymal stem cells (MMMSCs) from 10 multiple myeloma patients with a median age 60y...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27505710/sirt1-inhibits-inflammatory-response-partly-through-regulation-of-nlrp3-inflammasome-in-vascular-endothelial-cells
#20
Yanxiang Li, Ping Wang, Xiaofeng Yang, Weirong Wang, Jiye Zhang, Yanhao He, Wei Zhang, Ting Jing, Bo Wang, Rong Lin
Emerging evidence has indicated that vascular endothelial cells (ECs) not only form the barrier between blood and the vessel wall but also serve as conditional innate immune cells. Our previous study found that SIRT1, a class III histone deacetylase, inhibits the inflammatory response in ECs. Recent studies revealed that SIRT1 also participates in the modulation of immune responses. Although the NLRP3 inflammasome is known to be a crucial component of the innate immune system, there is no direct evidence demonstrating the anti-inflammatory effect of SIRT1 on ECs through the NLRP3 inflammasome...
September 2016: Molecular Immunology
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