| First Author | Johnson EN | Year | 1998 |
| Journal | Proc Natl Acad Sci U S A | Volume | 95 |
| Issue | 6 | Pages | 3100-5 |
| PubMed ID | 9501222 | Mgi Jnum | J:46896 |
| Mgi Id | MGI:1202206 | Doi | 10.1073/pnas.95.6.3100 |
| Citation | Johnson EN, et al. (1998) Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenase. Proc Natl Acad Sci U S A 95(6):3100-5 |
| abstractText | Arachidonic acid metabolism is one of several mechanisms culminating in the production of an agonist for platelet activation and recruitment. Although the proaggregatory role of thromboxane A(2), a product of the aspirin- inhibitable cyclooxygenase, is well established, relatively little is known regarding the biological importance of arachidonic acid metabolism via the 12- lipoxygenase (P-12LO) pathway to 12- hydro(pero)xyeicosatetraenoic acid. We observed that platelets obtained from mice in which the P-12LO gene has been disrupted by gene targeting (P-12LO(-/-)) exhibit a selective hypersensitivity to ADP, manifested as a marked increase in slope and percent aggregation in ex vivo assays and increased mortality in an ADP-induced mouse model of thromboembolism. The hyperresponsiveness to ADP is independent of dense granule release, cyclooxygenase- derived eicosanoid synthesis, and protein kinase C activity. The addition of 12-hydroxyeicosatetraenoic acid to P-12LO(-/-) platelet-rich plasma rescues the hyperresponsive phenotype resulting in a diminished ADP- induced aggregation profile. The enhanced ADP sensitivity of P-12LO(-/-) mice appears to reveal a mechanism by which a product of the P-12LO pathway suppresses platelet activation by ADP. |
