| First Author | Nonne C | Year | 2005 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 25 |
| Issue | 6 | Pages | 1293-8 |
| PubMed ID | 15774906 | Mgi Jnum | J:114266 |
| Mgi Id | MGI:3688678 | Doi | 10.1161/01.ATV.0000163184.02484.69 |
| Citation | Nonne C, et al. (2005) Importance of platelet phospholipase Cgamma2 signaling in arterial thrombosis as a function of lesion severity. Arterioscler Thromb Vasc Biol 25(6):1293-8 |
| abstractText | OBJECTIVE: Platelet activation occurs in response to adhesion receptors for von Willebrand factor (GPIb-V-IX) and collagen (GPVI and alpha2beta1 integrin) acting upstream of phospholipase C (PLC) gamma2. However, PLCbeta transduces signals from Galphaq protein-coupled receptors for soluble agonists (P2y1, TxA2/TP, and thrombin/PAR). A Gi-dependent pathway amplifies most of these responses. METHODS AND RESULTS: To evaluate the role of adhesion receptors signaling in arterial thrombosis, PLCgamma2 knockout mice were studied in blood perfusion assays over fibrillar collagen and in a laser-induced mesenteric artery model of thrombosis. In vitro, PLCgamma2-deficient platelets formed a single layer incapable of generating a thrombus on collagen, whereas Galphaq-deficient platelets formed reduced size aggregates compared with wild-type cells. In the in vivo model, PLCgamma2-/- mice displayed defective thrombus formation in superficial lesions but productive thrombosis after a more severe laser injury. In contrast, resistance to thrombosis was observed in Galphaq-/- mice in both levels of injury. CONCLUSIONS: These results demonstrate that signaling through PLCgamma2 plays an important role in arterial thrombosis, but that its contribution depends on the severity of the vascular lesion. |
