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histone deacetylase cardiovascular

Andrew J Yee, William I Bensinger, Jeffrey G Supko, Peter M Voorhees, Jesus G Berdeja, Paul G Richardson, Edward N Libby, Ellen E Wallace, Nicole E Birrer, Jill N Burke, David L Tamang, Min Yang, Simon S Jones, Catherine A Wheeler, Robert J Markelewicz, Noopur S Raje
BACKGROUND: Histone deacetylase (HDAC) inhibitors are an important new class of therapeutics for treating multiple myeloma. Ricolinostat (ACY-1215) is the first oral selective HDAC6 inhibitor with reduced class I HDAC activity to be studied clinically. Motivated by findings from preclinical studies showing potent synergistic activity with ricolinostat and lenalidomide, our goal was to assess the safety and preliminary activity of the combination of ricolinostat with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma...
September 16, 2016: Lancet Oncology
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
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
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
Ana Latorre, Antonio Moscardó
Reversible acetylation of histones is a well-known mechanism of epigenetic regulation of gene expression. More recently, studies have demonstrated that acetylation/deacetylation in several proteins regulate multiple aspects of cellular activity, especially those associated with energetic metabolism. Platelets are key participants in haemostasis and cardiovascular diseases. Although metabolic changes such as diabetes or lipidemia are well recognized risk factors for cardiovascular diseases, there is very little information about the relationship between metabolism and platelet reactivity...
September 7, 2016: Current Medicinal Chemistry
Yi Guan, Chuan-Ming Hao
BACKGROUND: SIRT1 is a nicotinamide adenine dinucleotide-dependent deacetylase belonging to the class III histone deacetylases. Abundantly expressed in the kidney, especially in the renal medulla, SIRT1 is closely involved in renal physiology and pathology. SUMMARY: SIRT1 targets both histone and nonhistone proteins, participates in many important signaling pathways and mediates the regulation of longevity, metabolic homeostasis, acute stress response and DNA integrity...
March 2016: Kidney Diseases
Joseph B Moore, John Zhao, Matthew C L Keith, Alok R Amraotkar, Marcin Wysoczynski, Kyung U Hong, Roberto Bolli
Histone deacetylase (HDAC) regulation is an essential process in myogenic differentiation. Inhibitors targeting the activity of specific HDAC family members have been shown to enhance the cardiogenic differentiation capacity of discrete progenitor cell types; a key property of donor cell populations contributing to their afforded benefits in cardiac cell therapy applications. The influence of HDAC inhibition on cardiac-derived mesenchymal stromal cell (CMC) transdifferentiation or the role of specific HDAC family members in dictating cardiovascular cell lineage specification has not been investigated...
August 9, 2016: Stem Cells
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...
August 3, 2016: Free Radical Biology & Medicine
Yi Lu, Yi-Dong Wang, Xiao-Ya Wang, Han Chen, Zhe-Jun Cai, Mei-Xiang Xiang
SIRT3 belongs to a highly conserved protein family of histone deacetylases and it is rich in mitochondria. As acetyl-modification is one of the important post-translational modifications that prevail in the mitochondria, it is not surprising that SIRT3 plays a key regulatory role in this organelle. SIRT3 has a wide range of substrates that are involved in the physiological and pathological processes of oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. These pathophysiological processes are considered as the underlying mechanisms of diseases like cardiac hypertrophy, myocardial infarction and heart failure, indicating the potential roles of SIRT3 in cardiovascular diseases...
October 1, 2016: International Journal of Cardiology
Peter J Barnes
Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation affecting predominantly the lung parenchyma and peripheral airways that results in largely irreversible and progressive airflow limitation. This inflammation is characterized by increased numbers of alveolar macrophages, neutrophils, T lymphocytes (predominantly TC1, TH1, and TH17 cells), and innate lymphoid cells recruited from the circulation. These cells and structural cells, including epithelial and endothelial cells and fibroblasts, secrete a variety of proinflammatory mediators, including cytokines, chemokines, growth factors, and lipid mediators...
July 2016: Journal of Allergy and Clinical Immunology
Gabriele Giacomo Schiattarella, Anna Sannino, Evelina Toscano, Fabio Cattaneo, Bruno Trimarco, Giovanni Esposito, Cinzia Perrino
No abstract text is available yet for this article.
September 15, 2016: International Journal of Cardiology
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
Yun Hak Kim, Jin Ung Bae, In Suk Kim, Chulhun L Chang, Sae Ock Oh, Chi Dae Kim
SIRT1, a class III histone deacetylase, is critically involved in cellular response to stress and modulates cardiovascular risk factors. However, its role in thrombus formation is largely unknown. Thus, this study investigated the effect of SIRT1 on pulmonary thrombus formation, and then identified its role in the modulation of platelet aggregation. In isolated human platelets, cell aggregation was increased by various platelet activators, such as platelet activating factor (PAF), arachidonic acid (AA), ADP, and thrombin...
June 8, 2016: Platelets
Vincenzo Carafa, Dante Rotili, Mariantonietta Forgione, Francesca Cuomo, Enrica Serretiello, Gebremedhin Solomon Hailu, Elina Jarho, Maija Lahtela-Kakkonen, Antonello Mai, Lucia Altucci
Sirtuins are NAD(+)-dependent histone deacetylases regulating important metabolic pathways in prokaryotes and eukaryotes and are involved in many biological processes such as cell survival, senescence, proliferation, apoptosis, DNA repair, cell metabolism, and caloric restriction. The seven members of this family of enzymes are considered potential targets for the treatment of human pathologies including neurodegenerative diseases, cardiovascular diseases, and cancer. Furthermore, recent interest focusing on sirtuin modulators as epigenetic players in the regulation of fundamental biological pathways has prompted increased efforts to discover new small molecules able to modify sirtuin activity...
2016: Clinical Epigenetics
Lillianne H Wright, Donald R Menick
Histone deacetylases (HDACs) play integral roles in many cardiovascular biological processes ranging from transcriptional and translational regulation to protein stabilization and localization. There are 18 known HDACs categorized into 4 classes that can differ on the basis of substrate targets, subcellular localization, and regulatory binding partners. HDACs are classically known for their ability to remove acetyl groups from histone and nonhistone proteins that have lysine residues. However, despite their nomenclature and classical functions, discoveries from many research groups over the past decade have suggested that nondeacetylase roles exist for class IIa HDACs...
July 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Sri N Batchu, Angela S Brijmohan, Andrew Advani
Recent years have witnessed an emergence of a new class of therapeutic agents, termed histone deacetylase 6 (HDAC6) inhibitors. HDAC6 is one isoform of a family of HDAC enzymes that catalyse the removal of functional acetyl groups from proteins. It stands out from its cousins in almost exclusively deacetylating cytoplasmic proteins, in exerting deacetylation-independent effects and in the success that has been achieved in developing relatively isoform-specific inhibitors of its enzymatic action that have reached clinical trial...
June 1, 2016: Clinical Science (1979-)
Vincent Zwick, Claudia Simões-Pires, Muriel Cuendet
Histone deacetylases (HDAC) are involved in several diseases including cancer, cardiovascular and neurodegenerative disorders, and the search for inhibitors is a current topic in drug discovery. Four HDAC inhibitors have already been approved by the FDA for cancer therapy and others are under clinical studies. However, the clinical utility of some of them is limited because of unfavorable toxicities associated with their broad range of HDAC inhibitory effects. Toxicity could be decreased by using HDAC inhibitors with improved specificity...
May 5, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
Nunzia D'Onofrio, Luigi Servillo, Alfonso Giovane, Rosario Casale, Milena Vitiello, Raffaele Marfella, Giuseppe Paolisso, Maria Luisa Balestrieri
Ergothioneine (Egt), the betaine of 2-mercapto-L-histidine, is a dietary antioxidant protecting against many diseases, including cardiovascular disease (CVD), through a redox mechanism different from alkylthiols. Here, experiments were designed to evaluate the mechanisms underlying the beneficial effect of Egt against hyperglycaemia-induced senescence in endothelial cells. To this end, cells were incubated with increasing concentrations of Egt (0.01-1.00mM) for 12h followed by incubation for 48h with high-glucose (25mM)...
July 2016: Free Radical Biology & Medicine
Rubén Jiménez-Canino, Fabián Lorenzo-Díaz, Frederic Jaisser, Nicolette Farman, Teresa Giraldez, Diego Alvarez de la Rosa
The mineralocorticoid receptor (MR) is a member of the nuclear receptor superfamily that transduces the biological effects of corticosteroids. Its best-characterized role is to enhance transepithelial sodium reabsorption in response to increased aldosterone levels. In addition, MR participates in other aldosterone- or glucocorticoid-controlled processes such as cardiovascular homeostasis, adipocyte differentiation or neurogenesis, and regulation of neuronal activity in the hippocampus. Like other steroid receptors, MR forms cytosolic heterocomplexes with heat shock protein (Hsp) 90), Hsp70, and other proteins such as immunophilins...
June 2016: Endocrinology
Baigalmaa Lkhagva, Yu-Hsun Kao, Yao-Chang Chen, Tze-Fan Chao, Shih-Ann Chen, Yi-Jen Chen
Atrial fibrillation (AF) is a common cardiac arrhythmia associated with high mortality and morbidity. Current treatments of AF have limited efficacy and considerable side effects. Histone deacetylases (HDACs) play critical roles in the pathophysiology of cardiovascular diseases and contribute to the genesis of AF. Therefore, HDAC inhibition may prove a novel therapeutic strategy for AF through upstream therapy and modifications of AF electrical and structural remodeling. In this review, we provide an update of the knowledge of the effects of HDACs and HDAC inhibitors on AF, and dissect potential underlying mechanisms...
June 15, 2016: European Journal of Pharmacology
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