经导管心脏介入术患者中蛋白酶激活受体-1 的性别特异性血小板激活。

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

机构信息

Center for Platelet Research Studies, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA; Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; Institute of Antithrombotic Therapy in Cardiovascular Disease, Karl Landsteiner Society, St. Poelten, Austria; Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria.

Center for Platelet Research Studies, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.

出版信息

Atherosclerosis. 2021 Dec;339:12-19. doi: 10.1016/j.atherosclerosis.2021.11.011. Epub 2021 Nov 12.

DOI:10.1016/j.atherosclerosis.2021.11.011

PMID:34808540

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.

摘要

背景与目的

蛋白酶激活受体（PAR）-1 介导的血小板激活可能因性别和临床情况而异。为了通过 PAR-1 研究性别特异性的血小板激活，我们评估了 562 例接受心脏导管检查的患者对血栓酶受体激活肽（TRAP）的血小板反应，其中无急性冠脉综合征（ACS）（第 1A 组）和有 ACS（第 1B 组）。随后，我们在 287 例接受择期（第 2A 组）或急性（第 2B 组）经皮冠状动脉介入治疗的患者中寻求证实我们的发现。

方法

在第 1 组中，通过流式细胞术测量 TRAP 刺激的血小板表面 P-选择素和活化糖蛋白 IIb/IIIa（GPIIb/IIIa）的表达。在第 2 组中，评估了对 TRAP 的光传输聚集（LTA）和多电极聚集（MEA）反应。

结果

在第 1A 组中，与男性相比，女性对 TRAP 的血小板激活明显更高（P-选择素：511 MFI [443-597 MFI] vs. 471 MFI [393-552 MFI]；GPIIb/IIIa：84 MFI [58-119 MFI] vs. 70 MFI [47-103 MFI]；均 p≤0.002）。相比之下，在第 1B 组中，男性和女性的 TRAP 刺激的 P-选择素和活化的 GPIIb/IIIa 相似（均 p≥0.3）。同样，第 2A 组中的女性患者的 TRAP 刺激的血小板聚集明显更高（LTA：66%[54-76%] vs. 51%[41-65%]；MEA：78 AU[66-107 AU] vs. 62 AU[52-88 AU]；均 p≤0.02），而第 2B 组中的男性和女性患者的血小板聚集相似（p=0.5）。第 1A 组和第 1B 组中的男性和女性患者的缺血终点发生率无显著差异。