Pleiotropic Effects of Ticagrelor: Influence on CYP4F2 Gene and Protein Expression in HUVEC and HepG2, and Escherichia coli Bacterial Survival

Ugne Meskauskaite,1 Silvija Andruskeviciute,1 Ieva Ciapiene,1 Agne Giedraitiene,2 Vaiva Lesauskaite,1 Vacis Tatarunas1 1Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania; 2Institute of Microbiology and Virology, Lithuanian University of Health Sciences, Kaunas, LithuaniaCorrespondence: Vacis Tatarunas, Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania, Tel +370 37302874, Email vacis.tatarunas@lsmuni.ltBackground: Antiplatelet drugs, such as ticagrelor, which target platelet P2Y12 receptors, are used for prevention of ischemic heart disease. Ticagrelor is also known to have pleiotropic effects of unknown mechanisms. Ticagrelor could influence the expression of molecules involved in resolution of inflammation. This study aimed to investigate if ticagrelor could change the expression of CYP4F2 and its encoded protein concentration and, additionally, to determine ticagrelor possible antibacterial activity against gram-negative bacteria.Methods: CYP4F2 expression was determined in HUVEC and HepG2 cell lines by qPCR. CYP4F2 protein concentration was determined by ELISA. Antibiotic susceptibility testing was performed using a disc diffusion method.Results: Ticagrelor was observed to reduce the expression of CYP4F2 in HUVEC and HepG2 cell lines. It also reduced CYP4F2 protein levels in HUVEC cells. Ticagrelor had no bactericidal activity against gram-negative third generation cephalosporin resistant E. coli.Conclusion: Ticagrelor reduced CYP4F2 protein concentration in HUVEC, and CYP4F2 expression in HUVEC and HepG2 cells, but had no effect on third-generation cephalosporin-resistant E. coli strains.Keywords: ticagrelor, HUVEC, HepG2, CYP4F2 gene, CYP4F2 protein, antimicrobial effect, ischemic heart disease