Title:Multidrug Resistance Protein 4 (MRP4/ABCC4): A Suspected Efflux Transporter for Human’s Platelet Activation
Volume: 28
Issue: 9
Author(s): Ioannis Angelis*, Vassilios Moussis, Demokritos C. Tsoukatos and Vassilios Tsikaris
Affiliation:
- Department of Chemistry, Faculty of Organic Chemistry & Biochemistry, University of Ioannina, Ioannina,Greece
Keywords:
MRP4/ABCC4, platelet, cAMP-compartmentalization, aspirin, antiplatelet target, Multidrug Resistance (MDR).
Abstract: The main role of platelets is to contribute to hemostasis. However, under pathophysiological
conditions, platelet activation may lead to thrombotic events of cardiovascular diseases.
Thus, anti-thrombotic treatment is important in patients with cardiovascular disease. This review focuses
on a platelet receptor, a transmembrane protein, the Multidrug Resistance Protein 4, MRP4,
which contributes to platelet activation, by extruding endogenous molecules responsible for their
activation and accumulation. The regulation of the intracellular concentration levels of these
molecules by MRP4 turned to make the protein suspicious and at the same time an interesting regulatory
factor of platelet normal function. Especially, the possible role of MRP4 in the excretion of
xenobiotic and antiplatelet drugs such as aspirin is discussed, thus imparting platelet aspirin tolerance
and correlating the protein with the ineffectiveness of aspirin antiplatelet therapy. Based on
the above, this review finally underlines that the development of a highly selective and targeted
strategy for platelet MRP4 inhibition will also lead to inhibition of platelet activation and accumulation.