Oral Presentation No. 090
Pleiotropic effect of antiplatelet ticagrelor: expression of CYP4F2 in HUVEC and HepG2

Ticagrelor is a first drug of a new chemical class cyclopentyltriazolopyrimidines and a third-generation P2Y₁₂ inhibitor that targets and directly binds platelet P2Y₁₂ receptors. It is recommended to be given as a dual antiplatelet therapy (DAPT) with aspirin for the prevention of thrombotic events and the following ischemic heart disease. Ticagrelor is also known to have pleiotropic effects of unknown mechanisms. It is questioned whether ticagrelor could influence the expression of cytochrome P450 4F2 (CYP4F2) enzyme involved in the resolution of inflammation and biosynthesis of pro-inflammatory eicosanoids. This study aimed to investigate if ticagrelor could alter the expression of CYP4F2 and its encoded protein concentration in both endothelial cells (human umbilical vein endothelial cells, HUVEC) and the metabolism of various xenobiotics performing, CYPs-rich liver cells (HepG2).

The expression of CYP4F2 was determined in HUVEC and HepG2 cell lines by qPCR on real time thermal cycler ABI 7900HT (Applied Biosystems, USA). CYP4F2 protein concentration was determined with sandwich enzyme immunoassay kit for CYP4F2 (Cloud-Clone Corp., USA).

Ticagrelor was observed to reduce the expression of CYP4F2 in HUVEC and HepG2 cell lines. It also reduced CYP4F2 protein levels in HUVEC cells. Thus, ticagrelor may have a protective role in endothelial cells and reduce vascular inflammation.

This work was supported by the Research Council of Lithuania under Grant 09.3.3.-LMT-K-712-16-0187.