And the Effects on the Downstream Signaling

pathways of FcgRIIa favor an intracellular mechanism for 12-LOX either directly through PLCg2 or via an upstream ITAM signaling complex (see figure). What is important is that this is the first demonstration that 12-LOX is involved in platelet activation through the immune Fc receptor FcgRIIa and as such may provide a viable therapeutic target for patients with HIT. It is also worth noting our own observation that following infusion of heparin, there is a significant release of 12-HETE in vivo, despite aspirin therapy, 14 suggesting 12-LOX may be even more intrinsically involved in the pathology of HIT. However, because 12-HETE has roles in other cells, the effect of inhibiting 12-LOX may have wider ranging effects that will be revealed through in vivo studies with inhibitors such as ML355. immunoreceptor tyrosine-based activation motif (ITAM) signaling and vascular integrity. Analysis, physiological and clinical significance of 12-HETE: a neglected platelet-derived 12-lipoxygenase product. A, et al. Synthesis and structure-activity relationship studies of