Hydrogen Sulfide―Releasing Aspirin Derivative ACS14 Exerts Strong Antithrombotic Effects In Vitro and In Vivo
In: Arteriosclerosis, thrombosis, and vascular biology, Jg. 32 (2012), Heft 12, S. 2884-2891
Online
academicJournal
- print, 46 ref
Zugriff:
Objective—Hydrogen sulfide (H2S)―releasing NSAIDs exert potent anti-inflammatory effects beyond classical cyclooxygenase inhibition. Here, we compared the platelet inhibitory effects of the H2S-releasing aspirin derivative ACS 14 with its mother compound aspirin to analyze additional effects on platelets. Methods and Results—In platelets of mice fed with ACS 14 for 6 days (50 mg/kg per day), not only arachidonic acid-induced platelet aggregation but also ADP-dependent aggregation was decreased, an effect that was not observed with an equimolar dose of aspirin (23 mg/kg per day). ACS 14 led to a significantly longer arterial occlusion time after light-dye-induced endothelial injury as well as decreased thrombus formation after ferric chloride-induced injury in the carotid artery. Bleeding time was not prolonged compared with animals treated with equimolar doses of aspirin. In vitro, in human whole blood, ACS 14 (25-500 μmol/L) inhibited arachidonic acid-induced platelet aggregation, but compared with aspirin additionally reduced thrombin receptor-activating peptide-, ADP-, and collagen-dependent aggregation. In washed human platelets, ACS14 (500 μmol/L) attenuated αIIbβ3 integrin activation and fibrinogen binding and increased intracellular cAMP levels and cAMP-dependent vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Conclusion—The H2S-releasing aspirin derivative ACS 14 exerts strong antiaggregatory effects by impairing the activation of the fibrinogen receptor by mechanisms involving increased intracellular cyclic nucleotides. These additional antithrombotic properties result in a more efficient inhibition of thrombus formation in vivo as achieved with aspirin alone.
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Hydrogen Sulfide―Releasing Aspirin Derivative ACS14 Exerts Strong Antithrombotic Effects In Vitro and In Vivo
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Autor/in / Beteiligte Person: | PIRCHER, Joachim ; FOCHLER, Franziska ; CZERMAK, Thomas ; MANNELL, Hanna ; KRAEMER, Bjoern F ; WÖRNLE, Markus ; SPARATORE, Anna ; DEL SOLDATO, Piero ; P, Ulrich ; KRÖTZ, Florian |
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Zeitschrift: | Arteriosclerosis, thrombosis, and vascular biology, Jg. 32 (2012), Heft 12, S. 2884-2891 |
Veröffentlichung: | Philadelphia, PA: Lippincott Williams & Wilkins, 2012 |
Medientyp: | academicJournal |
Umfang: | print, 46 ref |
ISSN: | 1079-5642 (print) |
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