(613a) 13c-MFA of Human Platelet Metabolism

Female sex hormones, like estrogen, can cause an increased risk for developing blood clots. Taking estrogen in the form of oral contraception increases the risk for venous thromboembolism (VTE) by approximately 3-4 fold. Platelets are blood cells critical for VTE initiation and propagation, yet the relationship between platelet function and sex hormones is unclear. Furthermore, current studies are contradictory, with reports of platelet activation being both inhibited and potentiated by acute exposure to estrogen. Estrogen is an important signaling molecule known to impact metabolism in many human tissues. However, the specific mechanisms by which estrogen might influence platelet metabolism is currently unknown.

Our work aims to characterize platelet metabolism during exposure to estrogen in order to identify the mechanisms by which platelet activation is modulated during response to platelet agonists (thrombin, ADP, collagen, etc.). Specifically, we are combining -omics technologies from a systems biology perspective to build metabolic models of platelet metabolism. We have performed intracellular metabolite profiling via mass spectroscopy and utilized carbon isotope labeling paired with metabolic flux analysis to inform our models of platelet central metabolism. We will present the results of these analyses and show flux maps of resting platelet metabolism. Additionally, we will discuss how the presence of estrogen alters carbon flux throughout the metabolism of human platelet cells.

(This project is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R61HL141794.)