(710e) Metabolomics for Investigating the Effects of Estrogen on Human Platelets

Exogenous female sex hormones can increase the risk of thrombosis, or excessive clotting. For example, there is a 3-4 fold increase in venous thromboembolism (VTE) for women taking oral contraception. Platelets play a role in the initiation and propagation of VTE, yet studies on the relationship between female sex hormones and platelet function are contradictory. For example, exposure to estrogen has been reported to both inhibit and potentiate thrombin-mediated platelet activation and aggregation.

Estrogen is known to interact with glucose and lipid metabolism in many human tissues (brain, muscle, adipose tissue). However, the mechanisms by which hormones like estrogen alter platelet metabolism are unknown. Our work aims to address this knowledge gap by characterizing platelet metabolism during estrogen exposure and identifying the mechanisms by which it modulates response to common platelet agonists (thrombin, ADP, collage). In pursuit of this goal, we are utilizing a systems biology approach by combining ­-omics technologies with metabolic modeling.

Our preliminary work with intracellular metabolite profiling via mass spectroscopy has shown significant decreases in glycolysis intermediates of estrogen-treated platelets, suggesting increases in platelet TCA cycle activity compared to untreated platelets. We will discuss these results as well as others from techniques such as carbon isotope labeling, metabolic flux analysis, and metabolic modeling. We also aim to discuss the implications of our metabolomics results on estrogen-induced modulation of central and fatty acid metabolism in human platelet cells.

(Research reported in this abstract was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R61HL141794.)