Variability in the Responsiveness to Low-Dose Aspirin: Pharmacological and Disease-Related Mechanisms
Figure 1
Cyclooxygenase-dependent arachidonic acid pathway in platelets. Thrombin, generated in vivo or ex vivo by several chemical or physical stimuli, activates its protease-activated receptors (PARs) increasing intraplatelet calcium, which triggers phospholipases (PL) A2-dependent cleavage of arachidonic acid (AA) from plasma membranes. AA is the enzymatic substrate of cyclooxygenase (COX)-1 and -2. COX-1-dependent AA path in platelets generates mainly TXA2 which amplifies platelet activation by binding to its platelet receptors (TPs). COX-2-dependent AA path in normal platelets is less prominent and generates mainly PGE2 which acts as a positive modulator of platelet response to other agonists by binding to its platelet receptors (EPs). TXA2 both in vivo or ex vivo is nonenzymatically hydrolized to TXB2, which is biologically inactive but stable, and can be measured in ex vivo assays or undergoes further hepatic enzymatic biotransformation in vivo.
