Remote ischemic preconditioning inhibits platelet αIIbβ3 activation in coronary artery disease patients receiving dual antiplatelet therapy

a randomized trial

Jerrett K. Lau, Gabrielle J. Pennings, Caroline J. Reddel, Heather Campbell, Hai Po H. Liang, Mathew Traini, Elizabeth E. Gardiner, Andy S. Yong, Vivien M. Chen, Leonard Kritharides*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Objectives: We investigated whether remote ischemic preconditioning (RIPC) inhibits agonist-induced conformational activation of platelet αIIbβ3 in patients with coronary artery disease already receiving conventional antiplatelet therapy. Patients/Methods: Consecutive patients with angiographically confirmed coronary artery disease were randomized to RIPC or sham treatment. Venous blood was collected before and immediately after RIPC/sham. Platelet aggregometry (ADP, arachidonic acid) and whole blood platelet flow cytometry was performed for CD62P, CD63, active αIIbβ3 (PAC-1 binding) before and after stimulation with ADP, thrombin ± collagen, or PAR-1 thrombin receptor agonist. Results: Patients (25 RIPC, 23 sham) were well matched, 83% male, age (mean ± standard deviation) 63.3 ± 13.2 years, 95% aspirin, 81% P2Y12 inhibitor. RIPC did not affect platelet aggregation, nor agonist-induced expression of CD62P, but selectively and significantly decreased αIIbβ3 activation after stimulation with either PAR-1 agonist peptide or the combination of thrombin + collagen, but not after ADP nor thrombin alone. The effect of RIPC on platelet αIIbβ3 activation was evident in patients receiving both aspirin and P2Y12 inhibitor, and was not associated with an increase in vasodilator-stimulated phosphoprotein phosphorylation. Conclusions: Remote ischemic preconditioning inhibits conformational activation of platelet αIIbβ3 in response to exposure to thrombin and collagen in patients with coronary artery disease receiving dual antiplatelet therapy. These findings indicate agonist-specific inhibition of platelet activation by RIPC in coronary artery disease that is not obviated by the prior use of P2Y12 inhibitors.

Original languageEnglish
Pages (from-to)1221-1232
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume18
Issue number5
DOIs
Publication statusPublished - May 2020
Externally publishedYes

Keywords

  • coronary artery disease
  • ischemic preconditioning
  • platelet activation
  • platelet antagonists
  • platelet glycoprotein GPIIb-IIIa complex

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