Beom Soo Kim1, David S Auerbach2, Hamza Sadhra1, Matthew Godwin3, Rohan Bhandari3,4, Frederick S Ling5, Amy Mohan1,5, David I Yule6, Larry Wagner6, David Q Rich1,7,8, Sara Ture1, Craig N Morrell1, Livia Timpanaro-Perrotta3, Arwa Younis, Ilan Goldenberg5, Scott J Cameron1,3,4. 1. Aab Cardiovascular Research Institute, University of Rochester School of Medicine, Rochester, New York (B.S.K., H.S., A.M., D.Q.R., S.T., C.N.M., S.J.C.). 2. Department of Pharmacology, SUNY Upstate Medical University, Syracuse, New York (D.S.A.). 3. Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute (M.G., R.B., L.T.-P., S.J.C.). 4. Department of Cardiovascular Medicine, Section of Vascular Medicine, Heart Vascular and Thoracic Institute (R.B., S.J.C.), Cleveland Clinic Foundation, OH. 5. Division of Cardiology, Department of Medicine (F.S.L., A.Y., I.G.), University of Rochester School of Medicine, New York. 6. Department of Pharmacology and Physiology (D.I.Y., L.W.), University of Rochester School of Medicine, New York. 7. Department of Public Health Sciences (D.Q.R.), University of Rochester School of Medicine, New York. 8. Department of Environmental Medicine (D.Q.R.), University of Rochester School of Medicine, New York.
Abstract
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 ST-segment-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. The divergent platelet phenotype in males and females at the time of MI suggests a sex-specific antiplatelet drug regimen should be prospectively evaluated.
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 ST-segment-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. The divergent platelet phenotype in males and females at the time of MI suggests a sex-specific antiplatelet drug regimen should be prospectively evaluated.
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