Genetic Variant in Human PAR (Protease-Activated Receptor) 4 Enhances Thrombus Formation Resulting in Resistance to Antiplatelet Therapeutics.

ABSTRACT:

Objective

Platelet activation after stimulation of PAR (protease-activated receptor) 4 is heightened in platelets from blacks compared with those from whites. The difference in PAR4 signaling by race is partially explained by a single-nucleotide variant in PAR4 encoding for either an alanine or threonine at amino acid 120 in the second transmembrane domain. The current study sought to determine whether the difference in PAR4 signaling by this PAR4 variant is because of biased G_q signaling and whether the difference in PAR4 activity results in resistance to traditional antiplatelet intervention.

Approach and results

Membranes expressing human PAR4-120 variants were reconstituted with either G_q or G₁₃ to determine the kinetics of G protein acti

SUBMITTER: Tourdot BE 

PROVIDER: S-EPMC6023764 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature