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https://www.readbyqxmd.com/read/28960024/new-aspects-of-vascular-calcification-histone-deacetylases-and-beyond
#1
REVIEW
Duk Hwa Kwon, Young Kook Kim, Hyun Kook
Vascular calcification is a pathologic phenomenon in which calcium phosphate is ectopically deposited in the arteries. Previously, calcification was considered to be a passive process in response to metabolic diseases, vascular or valvular diseases, or even aging. However, now calcification is recognized as a highly-regulated consequence, like bone formation, and many clinical trials have been carried out to elucidate the correlation between vascular calcification and cardiovascular events and mortality. As a result, vascular calcification has been implicated as an independent risk factor in cardiovascular diseases...
November 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28948877/insights-into-intermolecular-interactions-electrostatic-properties-and-the-stability-of-c646-in-the-binding-pocket-of-p300-histone-acetyltransferase-enzyme-a-combined-molecular-dynamics-and-charge-density-study
#2
Sivanandam Magudeeswaran, Saravanan Kandasamy, Kumaradhas Poomani
Histone acetyltransferases (HATs) and Histone deacetylases (HDACs) are enzymes exhibit important transcription activity. Dysfunction of these enzymes may lead to different diseases including cancer, cardiovascular and other diseases. Therefore, these enzymes are the potential target for the generation of new therapeutics. C646 is a synthetic p300 HAT inhibitor, its structural and the electrostatic properties are the paradigm to understand its activity in the active site of p300 HAT enzyme. The docked C646 molecule in the active site forms expected key intermolecular interactions with the amino acid residues Trp1436, Tyr1467 and one water molecule (W1861); and these interactions are important for acetylation reaction...
September 26, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28928236/histone-deacetylase-inhibition-ameliorates-hypertension-and-hyperglycemia-in-a-model-of-cushing-s-syndrome
#3
Hae-Ahm Lee, Seol-Hee Kang, Mina Kim, Eunjo Lee, Hyun-Min Cho, Eun-Kyung Moon, Inkyeom Kim
Cushing's syndrome (CS) caused by hypercortisolism is occasionally accompanied by metabolic disorders such as hypertension, diabetes mellitus (DM), dyslipidemia and central obesity. Thus, morbidity and mortality, observed in cardiovascular disease, are elevated in patients with CS. We hypothesized that HDAC inhibition (HDACi) decreased transcriptional activity of glucocorticoid receptor (GR), which ameliorates hypertension and hyperglycemia in patients with CS. To establish an animal model of hypercortisolism, Sprague-Dawley rats were infused with adrenocorticotropic hormone (ACTH, 40 ng/day) or dexamethasone (Dex, 10 μg/day) via osmotic minipumps for 4 weeks...
September 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28923781/low-dose-of-alcohol-attenuates-pro-atherosclerotic-activity-of-thrombin
#4
Masaaki Toda, Toshiaki Totoki, Chizu Nakamura, Taro Yasuma, Corina N D' Alessandro-Gabazza, Rumi Mifuji-Moroka, Kota Nishihama, Motoh Iwasa, Noriyuki Horiki, Esteban C Gabazza, Yoshiyuki Takei
BACKGROUND AND AIMS: Thrombin, the active enzyme of the coagulation system, plays a critical role in the pathogenesis of atherosclerosis. Vascular repair promoted by stromal cell-derived factor-1 is a protective process in atherosclerosis. Consumption of low amount of alcohol is believed to reduce the risk of atherosclerotic cardiovascular disease but the mechanism is unclear. This study evaluated whether alcohol can modulate the expression of stromal cell-derived factor-1 and the pro-atherosclerotic activity of thrombin...
September 5, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28804544/sirt3-attenuates-angii-induced-cardiac-fibrosis-by-inhibiting-myofibroblasts-transdifferentiation-via-stat3-nfatc2-pathway
#5
Xiaobin Guo, Fangying Yan, Jingyuan Li, Chunmei Zhang, Peili Bu
Cardiac fibrosis is a maladaptive response to various stresses, characterized by increased interstitial collagen deposition and progressive cardiac dysfunction. The transdifferentiation of fibroblasts into myofibroblasts is an essential process in the pathogenesis of cardiac fibrosis. SIRT3, as a mitochondrial NAD(+)-dependent histone deacetylase, has been demonstrated beneficial in many cardiovascular diseases. However, the specific mechanism of its protective role in cardiac fibrosis needs to be elucidated further...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28720877/role-of-the-histone-deacetylase-inhibitor-valproic-acid-in-high-fat-diet-induced-hypertension-via-inhibition-of-hdac1-angiotensin-ii-axis
#6
J Choi, S Park, T K Kwon, S I Sohn, K M Park, J I Kim
BACKGROUND: Obesity is known as an epidemic worldwide because of consumption of westernized high-fat diets and one of the major risk factors of hypertension. Histone deacetylases (HDACs) control gene expression by regulating histone/non-histone protein deacetylation. HDAC inhibitors exert anti-cancer and anti-inflammatory effects and play a protective role in cardiovascular diseases. In the present study, we tested the effect of an FDA-approved pan-HDAC inhibitor valproic acid (VPA) on high-fat diet (HFD)-induced hypertension in mice...
July 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28690765/novel-therapeutic-effects-of-leonurine-on-ischemic-stroke-new-mechanisms-of-bbb-integrity
#7
Qiu-Yan Zhang, Zhi-Jun Wang, De-Miao Sun, Ying Wang, Peng Xu, Wei-Jun Wu, Xin-Hua Liu, Yi-Zhun Zhu
Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198), a compound extracted from Herba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO) rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB) breakdown...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28678523/nutritional-biomarkers-current-view-and-future-perspectives
#8
Shubhra Pande, Valentina A Kratasyuk, Nadezhda N Medvedeva, Oxana A Kolenchukova, Alla B Salmina
There is a poor relationship between nutrient intake and existing nutritional biomarkers due to variety of factors affecting their sensitivity and specificity. To explore the impact of nutrients at molecular level and devising a sensitive biomarker, proteomics is a central technology with sirtuins as one of the most promising nutritional biomarker. Sirtuins (seven mammalian sirtuins reported so far) have been reported to perform protein deacetylases and ADP-ribosyltransferases activity. It is distributed in different cellular compartments thereby controlling several metabolic processes...
July 5, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28658542/the-nutrition-gut-microbiome-physiology-axis-and-allergic-diseases
#9
REVIEW
Craig McKenzie, Jian Tan, Laurence Macia, Charles R Mackay
Dietary and bacterial metabolites influence immune responses. This raises the question whether the increased incidence of allergies, asthma, some autoimmune diseases, cardiovascular disease, and others might relate to intake of unhealthy foods, and the decreased intake of dietary fiber. In recent years, new knowledge on the molecular mechanisms underpinning a 'diet-gut microbiota-physiology axis' has emerged to substantiate this idea. Fiber is fermented to short chain fatty acids (SCFAs), particularly acetate, butyrate, and propionate...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28634176/impact-of-glycemic-variability-on-chromatin-remodeling-oxidative-stress-and-endothelial-dysfunction-in-patients-with-type-2-diabetes-and-with-target-hba1c-levels
#10
Sarah Costantino, Francesco Paneni, Rodolfo Battista, Lorenzo Castello, Giuliana Capretti, Sergio Chiandotto, Luigi Tanese, Giulio Russo, Dario Pitocco, Gaetano A Lanza, Massimo Volpe, Thomas F Lüscher, Francesco Cosentino
Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D); however, the underlying mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigated whether epigenetic regulation of the adaptor protein p66(Shc), a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in patients with T2D despite IGC...
September 2017: Diabetes
https://www.readbyqxmd.com/read/28610961/histone-acetylation-favours-the-cardiovascular-commitment-of-adipose-tissue-derived-stromal-cells
#11
Elena De Falco, Antonella Bordin, Eleonora Scaccia, Francesca Pagano, Mohsen Ibrahim, Leonardo Schirone, Francesco Angelini, Silvia Palmerio, Michele Madonna, Luca Fianchini, Isotta Chimenti, Sebastiano Sciarretta, Giacomo Frati
BACKGROUND: Although adipose stromal cells (ASCs) retain the ability to transdifferentiate at low rate towards the cardiac lineage, the potential mechanisms underlying such process have still to be elucidated. METHODS: Since chromatin state modifications are involved in several processes regulating the cellular cell fate commitment, we aimed at evaluating the role of histone protein acetylation in the cardiovascular-like transdifferentiation of ASCs. RESULTS: We found a clear increase of histone 3 acetylation status paralleled by a significant upregulation of cardiac TnI gene expression, in ASCs treated with the conditioned medium of primary cardiomyocyte cell cultures for 72h...
September 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28576976/pleiotropic-and-adverse-effects-of-statins-do-epigenetics-play-a-role
#12
REVIEW
Stephanie C Allen, Cyril D S Mamotte
Statins are widely used to prevent major cardiovascular events by lowering serum cholesterol. There is evidence that statins have pleiotropic effects-that is, cholesterol-independent effects-that may also confer protection from cardiovascular disease and potentially numerous other pathologies, including cancer. Statins also have a number of well described adverse effects, including myopathy, rhabdomyolysis, liver damage, and type 2 diabetes. This paper examines the evidence of epigenetic modifications as a contributory factor to the pleiotropic and adverse effects of statins...
August 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28516248/environmental-toxicants-incidence-of-degenerative-diseases-and-therapies-from-the-epigenetic-point-of-view
#13
REVIEW
Mahshid Hodjat, Soheila Rahmani, Fazlullah Khan, Kamal Niaz, Mona Navaei-Nigjeh, Solmaz Mohammadi Nejad, Mohammad Abdollahi
Epigenotoxicology is an emerging field of study that investigates the non-genotoxic epigenetic effects of environmental toxicants resulting in alteration of normal gene expression and disruption of cell function. Recent findings on the role of toxicant-induced epigenetic modifications in the development of degenerative diseases have opened up a promising research direction to explore epigenetic therapy approaches and related prognostic biomarkers. In this review, we presented comprehensive data on epigenetic alterations identified in various diseases, including cancer, autoimmune disorders, pulmonary conditions as well as cardiovascular, gastrointestinal and bone disease...
July 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28498815/the-optimization-of-cell-therapy-by-combinational-application-with-apicidin-treated-mesenchymal-stem-cells-after-myocardial-infarction
#14
Dong Im Cho, Wan Seok Kang, Moon Hwa Hong, Hye Jin Kang, Mi Ra Kim, Min Chul Kim, Yong Sook Kim, Youngkeun Ahn
Although mesenchymal stem cells (MSC) have been shown to be safe in preclinical studies of cardiovascular disease, multiple meta-analyses have debated whether functional improvement is significant or not. The cardiac differentiation from MSC is achievable using cardiogenic factors, however, the high cost and long culture period may limit the applications. Here, we developed a novel method to optimize the therapeutic outcome for myocardial infarction (MI). Treatment of MSC with apicidin, a histone deacetylase inhibitor, dramatically increased the expressions of cardiac markers such as GATA4, Nkx2...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28485540/proteinase-activated-receptor-2-modulates-ve-cadherin-expression-to-affect-human-vascular-endothelial-barrier-function
#15
Rui Zhang, Jianjun Ge
Published data indicate that the protease-activated receptor (PAR) 2 is involved in the pathogenesis of some cardiovascular diseases; the underlying mechanism is to be further investigated. Ve-cadherin is a critical molecule in maintaining the endothelial barrier integrity. This study aims to investigate the role of PAR2 activation in compromising the cardiac endothelial barrier function. In this study, human umbilical vein endothelial cells (Huvec cells) were cultured into monolayers using as an in vitro model of barrier function...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28439316/epigenetic-assays-for-chemical-biology-and-drug-discovery
#16
REVIEW
Sheraz Gul
The implication of epigenetic abnormalities in many diseases and the approval of a number of compounds that modulate specific epigenetic targets in a therapeutically relevant manner in cancer specifically confirms that some of these targets are druggable by small molecules. Furthermore, a number of compounds are currently in clinical trials for other diseases including cardiovascular, neurological and metabolic disorders. Despite these advances, the approved treatments for cancer only extend progression-free survival for a relatively short time and being associated with significant side effects...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28382690/epigallocatechin-gallate-reverses-ctni-low-expression-induced-age-related-heart-diastolic-dysfunction-through-histone-acetylation-modification
#17
Bo Pan, Junjun Quan, Lingjuan Liu, Zhongwei Xu, Jing Zhu, Xupei Huang, Jie Tian
Cardiac diastolic dysfunction (CDD) is the most common form of cardiovascular disorders, especially in elderly people. Cardiac troponin I (cTnI) plays a critical role in the regulation of cardiac function, especially diastolic function. Our previous studies showed that cTnI-low expression induced by histone acetylation modification might be one of the causes that result in diastolic dysfunction in ageing hearts. This study was designed to investigate whether epigallocatechin-3-gallate (EGCG) would modify histone acetylation events to regulate cTnI expression and then improve cardiac functions in ageing mice...
October 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28191472/suppression-of-excessive-histone-deacetylases-activity-in-diabetic-hearts-attenuates-myocardial-ischemia-reperfusion-injury-via-mitochondria-apoptosis-pathway
#18
Yang Wu, Yan Leng, Qingtao Meng, Rui Xue, Bo Zhao, Liying Zhan, Zhongyuan Xia
Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28188215/cystathionine-%C3%AE-lyase-protects-vascular-endothelium-a-role-for-inhibition-of-histone-deacetylase-6
#19
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
https://www.readbyqxmd.com/read/28056545/histone-deacetylase-high-mobility-group-box-1-pathway-targeted-by-hypaconitine-suppresses-the-apoptosis-of-endothelial-cells
#20
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
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