The platelet phenotype in patients with ST-segment elevation myocardial infarction is different from non–ST-segment elevation myocardial infarction

Schmidt, Rachel; Morrell, Craig N.; Ling, Frederick S.; Simlote, Preya; Fernandez, Genaro; Rich, David Q.; Adler, David; Gervase, Joe; Cameron, Scott J.

doi:10.1016/j.trsl.2017.11.006

Cited by 25 publications

(30 citation statements)

References 52 publications

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“…Our sex-specific observations in platelet signaling following MI was most pronounced in NSTEMI compared to STEMI, validating previous reports that platelets in each condition may be fundamentally different (1,22,23). By multivariate regression analysis, it is potentially revealing that NSTEMI independently predicted both platelet PAR1 and thromboxane, but not P2Y 12 receptor signaling.…”

Section: Discussionsupporting

confidence: 88%

“…Determination of a gender-specific difference in these clinical situations as we present here is a logical extension of those previous studies. We previously reported that proteomic profiles, agonist sensitivity, and anti-platelet medication efficacy are altered in humans and in murine models of MI and peripheral artery disease (1,3). We now suggest, based on the present data, that platelets in patients with acute MI are primed toward augmented PAR signaling in men.…”

Section: Discussionsupporting

confidence: 62%

“…We used flow cytometry with measurement of platelet surface P-selectin to assess platelet function in a dose-dependent manner, as we have described previously (1). Platelet surface Pselectin is a marker of platelet alpha granule exocytosis in response to pharmacologic doses of platelet receptor agonists: ADP (P2Y 12 receptor), TRAP-6 (PAR1), and U46619 (thromboxane receptor).…”

Section: Platelet Functionmentioning

confidence: 99%

“…Anti-platelet therapy for patients following a diagnosis of MI consists of aspirin and a P2Y 12 receptor antagonists irrespective of whether the diagnosis is STEMI or NSTEMI. Recent data conducted in humans and in relevant murine models of MI and peripheral arterial disease (PAD) suggests the platelet phenotype, platelet receptor signaling, and responsiveness to antiplatelet medications are quite different from healthy platelets in which anti-platelet agents are first characterized (1)(2)(3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…Observational studies indicate long-term mortality for patients with NSTEMI remains greater than STEMI irrespective of appropriate cardiac catheterization and revascularization utilization (8,9). We previously reported in a small patient cohort that platelets from patients with NSTEMI show differences in post-receptor signal transduction pathways including the platelet PAR1 pathway compared to platelets from patients with STEMI or from healthy individuals (1).…”

Section: Introductionmentioning

confidence: 99%

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A Sex-Specific Switch in Platelet Receptor Signaling Following Myocardial Infarction

Kim

Auerbach

Sadhra

et al. 2019

Preprint

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Word Count: abstract 244 (abstract), 3639 (main) ABSTRACT BACKGROUND: A Sex-specific, personalized approach to anti-platelet therapy may be important in patients with myocardial infarction (MI). OBJECTIVES:Our goal was to determine whether platelets activate differently in healthy men and women compared to following MI. METHODS:Blood was obtained from healthy subjects or patients presenting acutely with STsegment Elevation Myocardial Infarction (STEMI) and non-ST Segment Elevation Myocardial Infarction (NSTEMI). Platelet function through surface receptor activation was examined in healthy subjects, in patients with MI, and in age-and strain-matched mice before and after MI.Multivariate regression analyses revealed clinical variables associated with platelet receptor sensitivity at the time of MI. RESULTS:Platelets from healthy women are dose-dependently more active compared to men, particularly through the platelet thromboxane signaling pathway (7.8-fold increase in women vs.3.0-fold in men, P=0.02). At the time of MI, platelet activation through surface proteaseactivated receptor 1 (PAR1) was less in women than men (3.5-fold vs. 8.5-fold, respectively, P=0.0001). Multivariate regression analyses revealed male sex (P=0.04) and NSTEMI (P=0.003) as independent predictors of enhanced platelet PAR1 signaling at the time of MI. Similar to humans, healthy female mice showed preferential thrombin-mediated platelet activation compared to male mice (8.7-fold vs. 4.8-fold, respectively; P<0.001). In the immediate post-MI environment, male mice showed preferential thrombin-mediated platelet activation compared to female mice (12.4-fold vs. 5.5-fold, respectively; P<0.001).3 CONCLUSIONS: These results outline a previously unrecognized sex-dependent platelet phenotype where inhibition of thrombin signaling in the peri-MI environment-particularly in males-may be an important consideration. CONDENSED ABSTRACTPreclinical studies evaluating anti-platelet drugs are generally conducted in platelets isolated from healthy individuals. Growing evidence suggests changes in platelet signaling properties in certain disease conditions compared to healthy platelets may alter the response to anti-platelet medications. This investigation revealed that platelets from men and women who are healthy and following MI signal differently, particularly through thromboxane and PAR1 receptors. This effect was especially noted in patients with NSTEMI compared to STEMI. These observations raise the possibility of considering a sex-specific anti-platelet regimen for males and females in atheroembolic vascular diseases such as NSTEMI..

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 62%

Section: Platelet Functionmentioning

confidence: 99%