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

José J Zamorano-León, Martin Gascón, Carlos H Martínez, Gala Freixer, Redy Guerra, Khaoula Zekri-Nechar, Esther Bernardo, Mariano de la Serna-Soto, Antonio Segura, Manel Giner, Miguel A García-Fernández, Carlos Macaya, Antonio J López-Farré

Journal: Journal of cardiovascular pharmacology 2021;76(5):584-591

PMID: 33170592

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.

Address: Department of Public Health and Maternal and Child Health, School of Medicine, Universidad Complutense, Madrid, Spain.; Health Care Department, General Headquarters, Spanish Navy, Madrid, Spain.; Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain.; Cardiology Department, Hospital Clínico San Carlos, Madrid, Spain.; Department of Health and Social Affairs, Health Institute of Talavera de la Reina, Toledo, Spain; and.; Department of Surgery, School of Medicine, Universidad Complutense, Madrid, Spain.
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