role of histone acetylation in the stimulatory effect of valproic acid on vascular endothelial tissue-type plasminogen activator expression组蛋白乙酰化的角色在丙戊酸的刺激作用血管内皮组织类型纤溶酶原激活物的表情.pdfVIP

Role of Histone Acetylation in the Stimulatory Effect of Valproic Acid on Vascular Endothelial Tissue-Type Plasminogen Activator Expression 1. 1. 1 1 2 2 Pia Larsson , Erik Ulfhammer , Mia Magnusson , Niklas Bergh , Sebastian Lunke , Assam El-Osta , 3 4 1 1 Robert L. Medcalf , Per-Arne Svensson , Lena Karlsson , Sverker Jern * 1The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 2 Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia, 3 Australian Centre for Blood Diseases, The Alfred Medical Research and Education Point, Monash University, Melbourne, Victoria, Australia, 4 Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Abstract Aims: Stimulated release of tissue-type plasminogen activator (t-PA) is pivotal for an intravascular fibrinolytic response and protects the circulation from occluding thrombosis. Hence, an impaired t-PA production is associated with increased risk for atherothrombotic events. A pharmacological means to stimulate the production of this enzyme may thus be desirable. We investigated if the anti-epileptic drug valproic acid (VPA) is capable of enhancing t-PA expression in vitro in vascular endothelial cells, and further examined if its histone deacetylase (HDAC)-inhibitory activity i