Eicosanoids in platelets and the effect of their modulation by aspirin in the cardiovascular system (and beyond)

Figure 1. Diagram of the biosynthesis of the main eicosanoids that affect platelet function and where it occurs. The yellow, green and red boxes represent the origin of the eicosanoids as platelets, ECs and leukocytes respectively. The receptors for each eicosanoid are shown as well as the associated effects on platelet activation.

Figure 2. Main pathways of eicosanoid‐mediated crosstalk between platelets and other cells. The eicosanoid exchanges between platelets and ECs and their effects on the vessel homeostasis are illustrated in (A) and (B). Some of the PGH2 released by platelets may be used by COX‐1 in the ECs to produce PGI2 which induces vasodilation and prevents further platelet activation (A). ECs, on the other hand, can synthesize EETs starting from AA, through the action of CYP450. EETs reduce platelet activation (B). (C) and (D) represent some routes of platelet‐leukocyte crosstalk. LTs are synthesized in leukocytes by 5‐LOX and act together with other agonists to potentiate platelet activation. However, platelets can also use LTs to make lipoxins which reduce the activation of platelets (C). 12‐LOX in platelets also produces epoxy‐resolvins that can be used by the leukocytes to make maresins, molecules important for the resolution of inflammation (D).

Figure 3. Schematic representation of platelet function tests used to monitor responses to aspirin in cardiovascular patients.

Figure 4. Effects of platelet COX‐1‐derived eicosanoids and of aspirin treatment in the progression of cancer. The preventive role of aspirin in the progression of cancer depends at least in part on its ability to block the formation of eicosanoids by platelet COX‐1. TXA2 and PGE2 are released in the tumour micro‐environment and favour the transformation of cells from a normal to a cancerous phenotype (A). 15‐HETE is another eicosanoid synthesised by COX‐1 in platelets that promotes angiogenesis, a process that further promotes cancer progression (B). TXA2 and PGE2 mediate the formation of platelet aggregates around the metastatic cancer cells, protecting them from the immune system and assisting their spread throughout the body (C).