The glycoprotein VI-phospholipase Cgamma2 signaling pathway controls thrombus formation induced by collagen and tissue factor in vitro and in vivo.
نویسندگان
چکیده
OBJECTIVE Both collagen and tissue factor can be initiating factors in thrombus formation. We investigated the signaling pathway of collagen-induced platelet activation in interaction with tissue factor-triggered coagulation during the thrombus-forming process. METHODS AND RESULTS In murine blood flowing over collagen, platelet exposure of phosphatidylserine and procoagulant activity, but not adhesion, completely relied on each of the following signaling modules: glycoprotein VI (GPVI), FcR gamma-chain, Src kinases, adaptor protein LAT, and phospholipase Cgamma2 (PLCgamma2). On flow in the presence of tissue factor, these signaling components were essential for platelet aggregation and greatly enhanced fibrin clot formation. Collagen-stimulated thrombin generation relied on the presence and activity of GPVI, FcR gamma-chain, Src kinase, LAT, and PLCgamma2. The physiological importance of this GPVI pathway was shown in a FeCl3-induced in vivo murine thrombosis model. In both venules and arterioles, signaling through GPVI, FcR gamma-chain, and Src kinases enhanced the formation of phosphatidylserine-exposing and fibrin-rich thrombi. CONCLUSIONS The GPVI-PLCgamma2 activation pathway regulates collagen-dependent coagulation in venous and arterial thrombus formation.
منابع مشابه
The Glycoprotein VI-Phospholipase C 2 Signaling Pathway Controls Thrombus Formation Induced by Collagen and Tissue Factor In Vitro and In Vivo
متن کامل
Dual role of collagen in factor XII-dependent thrombus formation.
In vivo mouse models have indicated that the intrinsic coagulation pathway, initiated by factor XII, contributes to thrombus formation in response to major vascular damage. Here, we show that fibrillar type I collagen provoked a dose-dependent shortening of the clotting time of human plasma via activation of factor XII. This activation was mediated by factor XII binding to collagen. Factor XII ...
متن کاملImportance of platelet phospholipase Cgamma2 signaling in arterial thrombosis as a function of lesion severity.
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. MET...
متن کاملThrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model.
Adhesion of platelets to an injured vessel wall and platelet activation are critical events in the formation of a thrombus. Of the agonists involved in platelet activation, thrombin, collagen, and vWF are known to induce in vitro calcium mobilization in platelets. Using a calcium-sensitive fluorochrome and digital multichannel intravital microscopy to image unstimulated and stimulated platelets...
متن کاملارتباط پلیمرفیسم T13254C گلیکوپروتئین VI پلاکتی با سکته حاد قلبی زودرس
Background and Aim: Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Epidemiological studies indicate that MI results from complex interactions between long-term environmental influences, concomitant disorders, and genetic susceptibility factors. Identification of genetic risk factors, particularly in premature MI, is very important. Since thrombosis plays a cri...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Arteriosclerosis, thrombosis, and vascular biology
دوره 25 12 شماره
صفحات -
تاریخ انتشار 2005