posted on 2021-02-25, 15:12authored byHang Liu, Hongyang Cui, Yixuan Huang, Shixiong Gao, Shu Tao, Jianying Hu, Yi Wan
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 A2, cardiolipin synthase,
and lysocardiolipin acyltransferase. Consequently, metabolic disorders
of CLs affected the levels of anticardiolipin antibodies, disrupted
the homeostasis between platelet thromboxane A2 and endothelial
prostacyclin, and promoted thrombotic events including heart ischemia
and tachycardia. Our study thus reveals the common molecular mechanisms
underlying the CL-induced thrombosis targeted by environmental exposures.