Hydrogen Sulfide–Releasing Aspirin Derivative ACS14 Exerts Strong Antithrombotic Effects In Vitro and In Vivo

• DOI: 10.1161/atvbaha.112.300627
• Publication Date: 2012-09-28T18:55:53Z
• Authors: Joachim Pircher; Franziska Fochler; Thomas Czermak; Hanna Mannell; Bjoern F. Kraemer; Markus Wörnle; Anna Sparatore; Piero Del Soldato; Ulrich Pohl; Florian Krötz
• Keywords: Derivative (finance)

Hydrogen sulfide (H(2)S)-releasing NSAIDs exert potent anti-inflammatory effects beyond classical cyclooxygenase inhibition. Here, we compared the platelet inhibitory of H(2)S-releasing aspirin derivative ACS14 with its mother compound to analyze additional on platelets.In platelets mice fed for 6 days (50 mg/kg per day), not only arachidonic acid-induced aggregation but also ADP-dependent was decreased, an effect that observed equimolar dose (23 day). led a significantly longer arterial occlusion time after light-dye-induced endothelial injury as well decreased thrombus formation ferric chloride-induced in carotid artery. Bleeding prolonged animals treated doses aspirin. In vitro, human whole blood, (25-500 µmol/L) inhibited aggregation, additionally reduced thrombin receptor-activating peptide-, ADP-, and collagen-dependent aggregation. washed platelets, (500 attenuated αIIbβ3 integrin activation fibrinogen binding increased intracellular cAMP levels cAMP-dependent vasodilator-stimulated phosphoprotein (VASP) phosphorylation.The exerts strong antiaggregatory by impairing receptor mechanisms involving cyclic nucleotides. These antithrombotic properties result more efficient inhibition vivo achieved alone.