Abstract
Background and aimsProtease-activated receptor (PAR)-1-mediated platelet activation may vary according to sex and clinical situation. In order to investigate sex-specific platelet activation through PAR-1, we assessed platelet response to thrombin receptor-activating peptide (TRAP) in 562 patients undergoing cardiac catheterization without (Group 1A) and with (Group 1B) acute coronary syndrome (ACS). Subsequently, we sought to confirm our findings in 287 patients undergoing elective (Group 2A) or acute (Group 2B) percutaneous coronary intervention. MethodsTRAP-stimulated platelet surface expression of P-selectin and activated glycoprotein IIb/IIIa (GPIIb/IIIa) were measured by flow cytometry in Group 1. Light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) in response to TRAP were assessed in Group 2. ResultsIn Group 1A, platelet activation in response to TRAP was significantly higher in women compared to men (P-selectin: 511 MFI [443–597 MFI] vs. 471 MFI [393–552 MFI]; GPIIb/IIIa: 84 MFI [58–119 MFI] vs. 70 MFI [47–103 MFI]; both p ≤ 0.002). In contrast, in Group 1B, TRAP-stimulated P-selectin and activated GPIIb/IIIa were similar in men and women (both p ≥ 0.3). Likewise, TRAP-stimulated platelet aggregation was significantly higher in female patients in Group 2A (LTA: 66% [54–76%] vs. 51% [41–65%]; MEA: 78 AU [66–107 AU] vs. 62 AU [52–88 AU]; both p ≤ 0.02), whereas men and women in Group 2 B had similar platelet aggregation (p = 0.5). The occurrence of ischemic endpoints did not differ significantly between men and women in Group 1A and Group 1B. ConclusionsPlatelet PAR-1 signaling is more pronounced in women than in men without ACS. In ACS, however, PAR-1-mediated platelet activation is similar in male and female patients.
Highlights
Antiplatelet therapy is a cornerstone of the treatment of atheroscle rotic cardiovascular disease [1,2]
We primarily investigated sex-specific platelet activa tion through protease-activated receptor (PAR)-1 in 562 patients undergoing cardiac catheterization without (Group 1A) and with (Group 1B) acute coronary syndrome (ACS)
We found significantly higher platelet PAR1-stimulated responses in women without ACS compared to men without ACS (Group 1A)
Summary
Antiplatelet therapy is a cornerstone of the treatment of atheroscle rotic cardiovascular disease [1,2]. Similar results were obtained in healthy mice and in a murine MI model when thrombin was used as platelet agonist [9] These findings point towards differences of PAR-1-mediated platelet activation between males and females in health and at the time of MI. In order to investigate sex-specific platelet activation through PAR-1, we assessed platelet response to thrombin receptor-activating peptide (TRAP) by flow cytometry in a large cohort of patients undergoing cardiac cathe terization without (Group 1A) and with (Group 1B) ACS. In order to investigate sex-specific platelet activation through PAR-1, we assessed platelet response to thrombin receptor-activating peptide (TRAP) in 562 patients undergoing cardiac catheterization without (Group 1A) and with (Group 1B) acute coronary syndrome (ACS). In ACS, PAR-1-mediated platelet activation is similar in male and female patients
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