Xenobiotics Targeting Cardiolipin Metabolism to Promote Thrombosis in Zebrafish.

Exposure to environmental pollutants is an important factor contributing to the development and severity of thrombosis. However, the important physiological molecules in the thrombotic processes affected by environmental exposures remain unknown. In this study, we show that exposure to environmental chemicals disrupts the equilibrium of cardiolipins (CLs), and directing CL synthesis promotes thrombosis. Using an untargeted metabolomics approach, approximately 3030 molecules were detected in zebrafish embryos exposed to 11 environmental chemicals and automatically clustered into a network. Interconnectivity among CLs and linoleates or isoxanthopterin was discovered through the highly consistent variations in the coregulated metabolites in the network. The chemical exposure resulted in significant upregulation of CLs through influencing the enzymatic activities of phospholipase A