Sex-Specific Platelet Activation through Protease-Activated Receptors Reverses in Myocardial Infarction

Beom Soo Kim, David S. Auerbach, Hamza Sadhra, Matthew Godwin, Rohan Bhandari, Frederick S. Ling, Amy Mohan, David I. Yule, Larry Wagner Ii, David Q. Rich, Sara Ture, Craig N. Morrell, Livia Timpanaro-Perrotta, Arwa Younis, Ilan Goldenberg, Scott J. Cameron

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: The platelet phenotype in certain patients and clinical contexts may differ from healthy conditions. We evaluated platelet activation through specific receptors in healthy men and women, comparing this to patients presenting with STsegment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. APPROACH AND RESULTS: We identified independent predictors of platelet activation through certain receptors and a murine MI model further explored these findings. Platelets from healthy women and female mice are more reactive through PARs (protease-activated receptors) compared with platelets from men and male mice. Multivariate regression analyses revealed male sex and non-ST-segment-elevation myocardial infarction as independent predictors of enhanced PAR1 activation in human platelets. Platelet PAR1 signaling decreased in women and increased in men during MI which was the opposite of what was observed during healthy conditions. Similarly, in mice, thrombin-mediated platelet activation was greater in healthy females compared with males, and lesser in females compared with males at the time of MI. CONCLUSIONS: Sex-specific signaling in platelets seems to be a cross-species phenomenon.

Original languageEnglish
Pages (from-to)390-400
Number of pages11
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number1
StatePublished - Jan 2021
Externally publishedYes


  • Female
  • Myocardial infarction
  • Platelet activation
  • Regression analysis
  • Thrombin


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