Sex-specific platelet activation through protease-activated receptor-1 in patients undergoing cardiac catheterization. (December 2021)

• Record Type: Journal Article
• Authors: Gremmel, Thomas; Michelson, Alan D.; Wadowski, Patricia P.; Pultar, Joseph; Weikert, Constantin; Tscharre, Maximilian; Lee, Silvia; Panzer, Simon; Frelinger, Andrew L.
• Is Part Of: Atherosclerosis. Volume 339(2021)
• Page Start: 12
• Page End: 19
• Publication Date: 2021-12
• Subjects: Sex -- Platelet activation -- Protease-activated receptor-1 -- Cardiac catheterization -- Acute coronary syndrome; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2021.11.011
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: Protease-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. Methods: TRAP-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. Results: In 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. Conclusions: Platelet 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. Graphical abstract: Image 1 Highlights: We investigated sex-specific platelet activation through PAR-1. We found significantly higher platelet PAR-1-stimulated responses in women without acute coronary syndrome (ACS) compared to men without ACS. In contrast, platelet activation in response to TRAP was similar in male and female ACS patients. PAR-1 signaling is more pronounced in women without ACS than in men without ACS. In patients with ACS, however, platelet PAR-1-stimulated responses are similar between women and men.