Abstract 143: Bridging the Gender Gap: Sex Differences in Von Willebrand Factor Aptamer Inhibition Across Species
| Autor: | Jeanne Green, Nicholas Musgrave, Allyson Huttinger, Spencer Talentino, David Dornbos, Cheyenne Jones, Nicholas Venetos, Shahid M Nimjee, Debra G Wheeler, Jay L. Zweier |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
biology business.industry medicine.disease Thrombosis Endocrinology Bolus (medicine) Von Willebrand factor In vivo Internal medicine Immunology medicine biology.protein Platelet Analysis of variance Platelet activation Cardiology and Cardiovascular Medicine business Ex vivo |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 37 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvb.37.suppl_1.143 |
| Popis: | Introduction: A gender gap exists in stroke, with increased morbidity and mortality in women. The underlying mechanisms remain unknown, although differences in platelet biology may play a role. Inhibition of the interaction between VWF and GP 1B-IX-V has demonstrated thrombolytic efficacy. Hypothesis: We hypothesized that sex differences in reperfusion after stroke were attributable to the VWF-GP IB-IX-V axis, and inhibition of this interaction would yield clear discrepancies. Methods: Adult wild-type (C57BL/6J) mice were anesthetized, the right carotid artery exposed and baseline carotid flow obtained by Doppler. Thrombosis was induced with a FeCl 3 patch. After 20-minute stabilization, mice were intravenously administered vehicle (n, male=12, female=8) or VWF aptamer. Aptamer (0.5 mg/kg) administration was assessed using a bolus (5 min; n, male=5, female=8) method. Given the minimal observed thrombolytic effect in females, a continuous infusion (45 min; n, female=5) was also attempted. Next, blood from male (n=8) and female (n=8) adult wild-type beagles was mixed with VWF aptamer (control, 6.25 nM, 12.5 nM, 25 nM, and 100 nM), and platelet reactivity was assessed (Platelet Function Analyser-100). Statistical analysis was performed using a two-way ANOVA with multiple comparisons. Results: Bolus VWF aptamer restored carotid blood flow in male mice (Figure 1), compared to females (p Male canines (264.3 ± 70.3 s) demonstrated significantly more platelet inhibition (p Conclusions: Following VWF inhibition, in vivo thrombolytic efficacy in mice is gender dependent, while ex vivo platelet activity varies in canines. The mechanisms underlying these differences in platelet biology are unclear, but this indicates that the VWF-GP IB-IX-V axis plays a role. |
| Databáze: | OpenAIRE |
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