Patricia P Wadowski1, Constantin Weikert1, Joseph Pultar1, Silvia Lee1, Beate Eichelberger2, Renate Koppensteiner1, Irene M Lang1, Simon Panzer2, Thomas Gremmel3,4. 1. Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. 2. Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria. 3. Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. thomas.gremmel@meduniwien.ac.at. 4. Department of Internal Medicine, Cardiology and Nephrology, Landesklinikum Wiener Neustadt, Wiener Neustadt, Austria. thomas.gremmel@meduniwien.ac.at.
Abstract
PURPOSE: Since ticagrelor inhibits the cellular uptake of adenosine, thereby increasing extracellular adenosine concentration and biological activity, we hypothesized that ticagrelor has adenosine-dependent antiplatelet properties. In the current study, we compared the effects of ticagrelor and prasugrel on platelet activation in acute coronary syndrome (ACS). METHODS: Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to adenosine diphosphate (ADP), the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, the TLR-4 agonist lipopolysaccharide (LPS), the protease-activated receptor (PAR)-1 agonist SFLLRN, and the PAR-4 agonist AYPGKF were measured by flow cytometry in blood from 80 ticagrelor- and 80 prasugrel-treated ACS patients on day 3 after percutaneous coronary intervention. Residual platelet aggregation to arachidonic acid (AA) and ADP were assessed by multiple electrode aggregometry and light transmission aggregometry. RESULTS: ADP-induced platelet activation and aggregation, and AA-induced platelet aggregation were similar in patients on ticagrelor and prasugrel, respectively (all p ≥ 0.3). Further, LPS-induced platelet surface expression of P-selectin and activated GPIIb/IIIa did not differ significantly between ticagrelor- and prasugrel-treated patients (both p > 0.4). In contrast, Pam3CSK4-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly lower in ticagrelor-treated patients (both p ≤ 0.005). Moreover, SFLLRN-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly less pronounced in patients on ticagrelor therapy compared to prasugrel-treated patients (both p < 0.03). Finally, PAR-4 mediated platelet activation as assessed by platelet surface expression of activated GPIIb/IIIa following stimulation with AYPGKF was significantly lower in patients receiving ticagrelor (p = 0.02). CONCLUSION: Ticagrelor inhibits TLR-1/2 and PAR mediated platelet activation in ACS patients more strongly than prasugrel.
PURPOSE: Since ticagrelor inhibits the cellular uptake of adenosine, thereby increasing extracellular adenosine concentration and biological activity, we hypothesized that ticagrelor has adenosine-dependent antiplatelet properties. In the current study, we compared the effects of ticagrelor and prasugrel on platelet activation in acute coronary syndrome (ACS). METHODS: Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to adenosine diphosphate (ADP), the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, the TLR-4 agonist lipopolysaccharide (LPS), the protease-activated receptor (PAR)-1 agonist SFLLRN, and the PAR-4 agonist AYPGKF were measured by flow cytometry in blood from 80 ticagrelor- and 80 prasugrel-treated ACSpatients on day 3 after percutaneous coronary intervention. Residual platelet aggregation to arachidonic acid (AA) and ADP were assessed by multiple electrode aggregometry and light transmission aggregometry. RESULTS:ADP-induced platelet activation and aggregation, and AA-induced platelet aggregation were similar in patients on ticagrelor and prasugrel, respectively (all p ≥ 0.3). Further, LPS-induced platelet surface expression of P-selectin and activated GPIIb/IIIa did not differ significantly between ticagrelor- and prasugrel-treated patients (both p > 0.4). In contrast, Pam3CSK4-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly lower in ticagrelor-treated patients (both p ≤ 0.005). Moreover, SFLLRN-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly less pronounced in patients on ticagrelor therapy compared to prasugrel-treated patients (both p < 0.03). Finally, PAR-4 mediated platelet activation as assessed by platelet surface expression of activated GPIIb/IIIa following stimulation with AYPGKF was significantly lower in patients receiving ticagrelor (p = 0.02). CONCLUSION:Ticagrelor inhibits TLR-1/2 and PAR mediated platelet activation in ACSpatients more strongly than prasugrel.
Authors: Hana Seung; Jan Wrobel; Carolin Wadle; Timon Bühler; Diana Chiang; Jasmin Rettkowski; Nina Cabezas-Wallscheid; Béatrice Hechler; Peter Stachon; Alexander Maier; Christian Weber; Dennis Wolf; Daniel Duerschmied; Marco Idzko; Christoph Bode; Constantin von Zur Mühlen; Ingo Hilgendorf; Timo Heidt Journal: Basic Res Cardiol Date: 2022-03-30 Impact factor: 12.416
Authors: Silvia Lee; Patricia P Wadowski; Timothy Hoberstorfer; Constantin Weikert; Joseph Pultar; Christoph W Kopp; Simon Panzer; Thomas Gremmel Journal: Cardiovasc Drugs Ther Date: 2020-08-26 Impact factor: 3.727
Authors: Maximilian Tscharre; Patricia P Wadowski; Constantin Weikert; Joseph Pultar; Beate Eichelberger; Simon Panzer; Thomas Gremmel Journal: Cardiovasc Drugs Ther Date: 2020-12-18 Impact factor: 3.727
Authors: Patricia P Wadowski; Joseph Pultar; Constantin Weikert; Beate Eichelberger; Irene M Lang; Renate Koppensteiner; Simon Panzer; Thomas Gremmel Journal: J Cardiovasc Pharmacol Ther Date: 2020-10-27 Impact factor: 2.457