Ticagrelor Inhibits Toll-Like and Protease-Activated Receptor Mediated Platelet Activation in Acute Coronary Syndromes.
Acute Coronary Syndrome
/ blood
Aged
Blood Platelets
/ drug effects
Female
Humans
Male
Middle Aged
P-Selectin
/ metabolism
Percutaneous Coronary Intervention
/ adverse effects
Platelet Aggregation
/ drug effects
Platelet Aggregation Inhibitors
/ therapeutic use
Platelet Glycoprotein GPIIb-IIIa Complex
/ metabolism
Prasugrel Hydrochloride
/ therapeutic use
Purinergic P2Y Receptor Antagonists
/ therapeutic use
Receptors, Proteinase-Activated
/ metabolism
Signal Transduction
Ticagrelor
/ therapeutic use
Toll-Like Receptors
/ metabolism
Treatment Outcome
Antiplatelet therapy
Cardiovascular disease
P2Y12 antagonists
Protease-activated receptors
Toll-like receptors
Journal
Cardiovascular drugs and therapy
ISSN: 1573-7241
Titre abrégé: Cardiovasc Drugs Ther
Pays: United States
ID NLM: 8712220
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
pubmed:
18
2
2020
medline:
21
10
2020
entrez:
17
2
2020
Statut:
ppublish
Résumé
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). 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. 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). Ticagrelor inhibits TLR-1/2 and PAR mediated platelet activation in ACS patients more strongly than prasugrel.
Identifiants
pubmed: 32062795
doi: 10.1007/s10557-019-06932-7
pii: 10.1007/s10557-019-06932-7
pmc: PMC7093367
doi:
Substances chimiques
P-Selectin
0
Platelet Aggregation Inhibitors
0
Platelet Glycoprotein GPIIb-IIIa Complex
0
Purinergic P2Y Receptor Antagonists
0
Receptors, Proteinase-Activated
0
SELP protein, human
0
Toll-Like Receptors
0
Prasugrel Hydrochloride
G89JQ59I13
Ticagrelor
GLH0314RVC
Types de publication
Comparative Study
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
53-63Références
Nat Rev Drug Discov. 2010 Feb;9(2):154-69
pubmed: 20118963
Mol Pharmacol. 2017 Jan;91(1):39-47
pubmed: 27784794
Curr Cardiol Rev. 2009 Aug;5(3):196-202
pubmed: 20676278
J Am Coll Cardiol. 1999 Nov 1;34(5):1420-6
pubmed: 10551687
J Am Coll Cardiol. 2014 Mar 11;63(9):872-7
pubmed: 24291273
N Engl J Med. 2007 Nov 15;357(20):2001-15
pubmed: 17982182
Thromb Haemost. 2017 Nov;117(11):2013-2025
pubmed: 29044290
Res Pract Thromb Haemost. 2018 May 27;2(3):439-449
pubmed: 30046748
J Am Coll Cardiol. 2014 Jun 17;63(23):2503-2509
pubmed: 24768873
Cardiovasc Ther. 2013 Oct;31(5):e40-5
pubmed: 23311679
Eur J Clin Invest. 2013 Jul;43(7):689-97
pubmed: 23611368
Eur Heart J. 2016 Nov 21;37(44):3343-3346
pubmed: 27593104
J Biol Chem. 2000 Jul 21;275(29):21785-8
pubmed: 10801897
J Thromb Haemost. 2013 Apr 10;:
pubmed: 23574625
J Biol Chem. 2000 Jun 30;275(26):19728-34
pubmed: 10779527
J Clin Invest. 1999 Mar;103(6):879-87
pubmed: 10079109
Am J Cardiol. 2015 Dec 1;116(11):1666-71
pubmed: 26455385
Thromb Haemost. 2015 Apr;113(4):806-12
pubmed: 25428141
Am J Pathol. 1986 Aug;124(2):324-34
pubmed: 2943164
Thromb Haemost. 2009 Feb;101(2):333-9
pubmed: 19190818
J Immunol. 2008 Sep 1;181(5):3495-502
pubmed: 18714022
Semin Thromb Hemost. 2016 Apr;42(3):191-204
pubmed: 26926581
Thromb Haemost. 2015 May;113(5):1035-45
pubmed: 25716539
Arterioscler Thromb Vasc Biol. 2018 Jun;38(6):1252-1254
pubmed: 29793990
Thromb Res. 2010 Mar;125(3):205-9
pubmed: 19945154
Int J Cardiol. 2017 Dec 15;249:66-72
pubmed: 29121759
N Engl J Med. 2009 Sep 10;361(11):1045-57
pubmed: 19717846
Sci Transl Med. 2017 Jan 4;9(371):
pubmed: 28053157
Biochemistry. 1999 Feb 23;38(8):2486-93
pubmed: 10029543
Nature. 1998 Aug 13;394(6694):690-4
pubmed: 9716134
J Cardiovasc Transl Res. 2017 Aug;10(4):359-367
pubmed: 28425039
J Biol Chem. 1999 Apr 16;274(16):10689-92
pubmed: 10196138
Front Immunol. 2015 Mar 02;6:83
pubmed: 25784910
J Thromb Haemost. 2018 Dec;16(12):2501-2514
pubmed: 30347494
J Am Coll Cardiol. 2016 Sep 6;68(10):1082-115
pubmed: 27036918
J Am Coll Cardiol. 2014 Sep 2;64(9):863-71
pubmed: 25169169
Thromb Haemost. 2010 Feb;103(2):398-407
pubmed: 20024498
Vasa. 2019 Jul;48(4):291-302
pubmed: 30324870
Can J Cardiol. 2018 Dec;34(12):1606-1612
pubmed: 30527148
Thromb Res. 2017 Oct;158:8-15
pubmed: 28783513
Arterioscler Thromb Vasc Biol. 2018 Feb;38(2):448-456
pubmed: 29269513
Eur Heart J. 2018 Jan 14;39(3):213-260
pubmed: 28886622
Eur J Clin Invest. 2018 Jan;48(1):
pubmed: 29171876
Thromb Res. 2003;111(1-2):65-73
pubmed: 14644082
J Cardiovasc Pharmacol Ther. 2014 Mar;19(2):209-19
pubmed: 24414167
J Am Coll Cardiol. 2018 Jan 30;71(4):371-381
pubmed: 29154813
Thromb Haemost. 2006 Dec;96(6):781-8
pubmed: 17139373
Circ Res. 2012 Jan 6;110(1):116-25
pubmed: 22223209
J Thromb Haemost. 2013 Oct;11(10):1867-76
pubmed: 23890048
Circ Res. 2011 Apr 29;108(9):1133-45
pubmed: 21527743
Eur Heart J. 2006 Oct;27(20):2420-5
pubmed: 17005534
N Engl J Med. 2012 Jan 5;366(1):20-33
pubmed: 22077816
J Am Coll Cardiol. 2012 Jul 17;60(3):193-9
pubmed: 22789884
J Am Coll Cardiol. 2003 Mar 19;41(6):961-5
pubmed: 12651041
Thromb Haemost. 2014 Mar 3;111(3):474-82
pubmed: 24196591
Circ Cardiovasc Interv. 2012 Dec;5(6):797-804
pubmed: 23169985
Cell. 1992 Apr 3;69(1):11-25
pubmed: 1555235
Am Heart J. 2007 Jan;153(1):66.e9-16
pubmed: 17174640
Methods. 2000 Jul;21(3):259-70
pubmed: 10873480
Eur Heart J. 2006 May;27(10):1166-73
pubmed: 16621870
Front Biosci (Landmark Ed). 2017 Jun 1;22:1867-1883
pubmed: 28410150
Blood. 1998 Jan 1;91(1):134-41
pubmed: 9414277
Int J Cardiol. 2013 Sep 20;168(1):403-6
pubmed: 23041015
Res Pract Thromb Haemost. 2019 May 22;3(3):383-390
pubmed: 31294325
J Thromb Haemost. 2008 Apr;6(4):677-83
pubmed: 18182038
Platelets. 2019;30(5):599-607
pubmed: 29869943
Pharmacotherapy. 2014 Oct;34(10):1077-90
pubmed: 25164528
J Am Coll Cardiol. 2013 Dec 17;62(24):2261-73
pubmed: 24076493
Clin Sci (Lond). 2016 Mar;130(6):433-40
pubmed: 26554025
J Exp Med. 1991 Oct 1;174(4):785-90
pubmed: 1680957
Chest. 2003 Sep;124(3 Suppl):18S-25S
pubmed: 12970120
Thromb Res. 2012 Mar;129(3):250-6
pubmed: 22137742