(579b) Quantification of Changes to Platelet Central Carbon Metabolism upon Acute Estrogen Exposure

Platelets, while essential to human health, are implicated in severe health problems such as heart attacks, strokes, and venous thrombosis. Pre-menopausal women have lower incidences of these events compared to post-menopausal women and men, leading to a hypothesis that estrogen has a cardioprotective effect (Maccarrone et al 2015, Khetawat et al 2000). However, it has also been observed that women on hormonal oral contraceptives are at an increased risk (4-6 fold) of venous thrombosis (Vinogradova et al 2015). Conflicting studies exist on the effect of estrogen on platelets both in vivoand ex vivo (Grodstein et al 2000, Cushman et al 2004, Bar et al 2000, Moro et al 2005). Here, we apply metabolomic and fluxomic techniques to quantify changes in platelet metabolism upon acute exposure to physiologically relevant concentrations of estrogen. We measure glucose, lactate, glycogen, and acetate flux to characterize central carbon metabolism of estrogen treated platelets from both male and female donors. Additionally, we probe whether these changes are mediated by platelet estrogen receptors by using ICI 182,780, a potent estrogen receptor antagonist. Quantifying changes in metabolism upon acute estrogen exposure may help explain the increased risk of venous thrombosis in people using combined oral contraceptives, as well as explain sexual dimorphisms in platelet behavior in vivo.

References:

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