Farnesyl Pyrophosphate and ADP-mediated Platelet Aggregation

Read this article recently and it seems interesting. Farnesyl pyrophosphate (FPP) can itself activate platelets and can induce platelet aggregation. However, this study concludes that FPP can act as endogenous antithrombotic factor by acting as insurmountable antagonist of ADP-mediated platelet aggregation. FPP is an intermediate in the cholesterol biosynthetic pathway. FPP also serves as a donor in post-translational isoprenylation of proteins. The steady-state plasma level was reported to be 6.6 ng/ml,  but  even  the  mild  physiological alteration caused by eating a meal has been demonstrated to increase the plasma concentration 200 fold. FPP is a natural antagonist of the LPA₂  (lysophosphatidic acid type 2) and LPA₃  receptors, and an agonist at the LPA₄  and LPA₅ receptors. While these receptors are present in platelets, FPP doesn’t appear to act through these receptors. Hogberg et al realized that the structure of ADP and FPP is similar as are their receptors. Thus, through a series of experiments they should that FPP inhibits platelet aggregation by blocking ADP receptors.