Role of Histone Acetylation in the Stimulatory Effect of Valproic Acid on Vascular Endothelial Tissue-Type Plasminogen Activator Expression
Pia Larsson, Erik Ulfhammer, Mia Magnusson, Niklas Bergh, Sebastian Lunke, Assam El-Osta, Robert L Medcalf, Per-Arne Svensson, Lena Karlsson, Sverker Jern
PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2012
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 is of importance for regulating t-PA expression. METHODS AND RESULTS: Human endothelial cells were exposed to valpr..View full abstract
Awarded by Swedish Research Council
This work was supported by research grants from the Swedish Research Council (http://www.vr.se/)(project no. 15038 and 20758), the Swedish Heart-Lung Foundation (http://www.hjart-lungfonden.se/), the Swedish Hypertension Society, the Sahlgrenska Academy at Goteborg University, King Gustaf V:s and Queen Victoria Foundation, King Gustaf V:s 80-year Foundation, Petrus and Augusta Hedlund's Foundation, Emelle Foundation, and Lars Hierta Memorial Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.