Platelet Apoptotic Response May Be Associated With the Capacity of Aspirin to Inhibit Platelets

J Cardiovasc Pharmacol. 2020 Nov;76(5):584-591. doi: 10.1097/FJC.0000000000000908.

Abstract

An inadequate platelet response to aspirin (ASA) has been identified in some patients under chronic ASA treatment. The aim of this study was to analyze if ASA-sensitive and ASA-resistant platelets have differences in their apoptotic capability. Clinically stable ischemic coronary patients who had been taking ASA (100 mg/d) for at least 9 months before inclusion were divided into ASA-resistant (n = 11) and ASA-sensitive (n = 13) groups as defined by the PFA-100 test. Platelets from ASA-sensitive patients showed higher expression of the proapoptotic proteins Bak and Bax than those from ASA-resistant patients, although only Bak protein remained different when the results were adjusted by age. In resting platelets, neither caspase-3 activity nor cytosolic cytochrome C levels were different between both experimental groups. Stimulation of platelets with calcium ionophore (10 nmol/L, A23187) increased caspase-3 activity (1.91-fold higher; P < 0.05) and cytosolic cytochrome C levels (1.84-fold higher; P < 0.05) to a higher degree in ASA-sensitive than in ASA-resistant platelets. In conclusion, ASA-sensitive platelets seem to be better prepared to undergo apoptosis during robust platelet activation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / blood*
  • Aspirin / therapeutic use*
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • Calcimycin / pharmacology
  • Calcium Ionophores / pharmacology
  • Caspase 3 / blood
  • Drug Resistance
  • Electron Transport Complex IV / blood
  • Female
  • Humans
  • Male
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / pathology
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Treatment Outcome
  • bcl-2 Homologous Antagonist-Killer Protein / blood
  • bcl-2-Associated X Protein / blood

Substances

  • Apoptosis Regulatory Proteins
  • BAK1 protein, human
  • BAX protein, human
  • Calcium Ionophores
  • Platelet Aggregation Inhibitors
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • Calcimycin
  • Electron Transport Complex IV
  • CASP3 protein, human
  • Caspase 3
  • Aspirin