| First Author | Yeung J | Year | 2013 |
| Journal | Thromb Haemost | Volume | 110 |
| Issue | 3 | Pages | 569-81 |
| PubMed ID | 23784669 | Mgi Jnum | J:268842 |
| Mgi Id | MGI:6272455 | Doi | 10.1160/TH13-01-0014 |
| Citation | Yeung J, et al. (2013) 12-lipoxygenase activity plays an important role in PAR4 and GPVI-mediated platelet reactivity. Thromb Haemost 110(3):569-81 |
| abstractText | Following initial platelet activation, arachidonic acid is metabolised by cyclooxygenase-1 and 12-lipoxygenase (12-LOX). While the role of 12-LOX in the platelet is not well defined, recent evidence suggests that it may be important for regulation of platelet activity and is agonist-specific in the manner in which it regulates platelet function. Using small molecule inhibitors selective for 12-LOX and 12-LOX-deficient mice, the role of 12-LOX in regulation of human platelet activation and thrombosis was investigated. Pharmacologically inhibiting 12-LOX resulted in attenuation of platelet aggregation, selective inhibition of dense versus alpha granule secretion, and inhibition of platelet adhesion under flow for PAR4 and collagen. Additionally, 12-LOX-deficient mice showed attenuated integrin activity to PAR4-AP and convulxin compared to wild-type mice. Finally, platelet activation by PARs was shown to be differentially dependent on COX-1 and 12-LOX with PAR1 relying on COX-1 oxidation of arachidonic acid while PAR4 being more dependent on 12-LOX for normal platelet function. These studies demonstrate an important role for 12-LOX in regulating platelet activation and thrombosis. Furthermore, the data presented here provide a basis for potentially targeting 12-LOX as a means to attenuate unwanted platelet activation and clot formation. |
