Enhanced responsiveness of platelets to vicagrel in IL-10-deficient mice through STAT3-dependent up-regulation of the hydrolase arylacetamide deacetylase in the intestine.

ABSTRACT:

Background and purpose

Vicagrel is a novel promising antiplatelet drug designed for overcoming clopidogrel resistance. There is limited evidence indicating that exogenous IL-10 suppresses CYP3A4 activity in healthy subjects and that IL-10 knockout (KO) mice exhibit increased clopidogrel bioactivation compared with wild-type (WT) mice. In this study, we sought to determine whether IL-10 could play an important role in the metabolism of and platelet response to vicagrel in mice.

Experimental approach

IL-10 KO and WT mice were administered vicagrel, then their plasma H4 (active metabolite of vicagrel) concentrations were determined by LC-MS/MS, and inhibition of ADP-induced whole-blood platelet aggregation by vicagrel was assessed with an aggregometer. The mRNA and protein leve

SUBMITTER: Jia YM 

PROVIDER: S-EPMC6514289 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature