Abstract Number: PB1705
Meeting: ISTH 2020 Congress
Background: Aberrant platelet activation causes thrombotic diseases. In physiological state, platelet homeostasis is maintained by inhibitory factors, including prostaglandin (PG) I2, NO, and CD39. Antiplatelet drugs are needed for patients at risk of thrombosis, such as patients after percutaneous coronary intervention. However, existing antiplatelet drugs increase the risk of bleeding. Therefore, it is particularly important to further study physiological inhibition factors of platelet homeostasis. Recently, we found that bile acids inhibit aggregation of platelets.
Aims: Explore functions of bile acids in platelet activation and clarify mechanisms of bile acids in platelet homeostasis.
Methods: Platelet aggregation and flow cytometric analysis were used to explore function of bile acids in platelet activation. Phosphoproteomic profiling and Western blots were used to explore mechanisms of lithocholic acid (LCA) in platelet aggregation. Ferric chloride-induced carotid injury model was used to establish the influence of LCA on thrombus formation in Bile acids receptor (G Protein-Coupled Bile Acid Receptor 1, GPBAR1) knockout mice.
Results: Among bile acids, LCA significantly inhibitory the collagen induced platelet aggregation. Phosphorylated proteomics analysis revealed that p38, MAPK3, JNK etc. may take part in inhibiting platelet activation by LCA (Fig.1). Western blot assays revealed that LCA regulate platelet activation via p38 and Akt pathway (Fig.2). In addition, in the process of platelet activation, the inhibition of LCA on Ca2+ internal flow exhibited a dose-dependent effect. The average time to first occlusion for the GPBAR1-/- mice was 5.417±0.538 minutes, in contrast to 6.825±0.492 minutes (P＜0.01) in the wild type mice.
Conclusions: LCA controls platelet activation via p38 and Akt pathway. Bile acids affect Ca2+ internal flow as well as in arterial thrombus formation in vivo. Therefore, bile acids take part in maintenance of platelet homeostasis and may reduce the risk of thrombotic disease. Anti-platelet studies of bile acids provide theoretical basis for the development of new antiplatelet agents.
To cite this abstract in AMA style:Cheng Z, Zhou X, Mei H, Hu Y. Bile Acids Maintain Platelet Homeostasis via p38 and Akt Pathway [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/bile-acids-maintain-platelet-homeostasis-via-p38-and-akt-pathway/. Accessed May 18, 2021.
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