Role of p38 Mitogen-Activated Protein Kinase in Thrombus Formation

Abstract

The present study was designed to elucidate the role of p38 mitogen-activated protein kinase (p38) in thrombus formation. We used p38α heterozygous (p38α+/−) mice and used ferric chloride (FeCl₃)-induced carotid artery injury as a model of thrombus formation. The time to thrombotic occlusion induced by FeCl₃ in p38α+/− mice was prolonged compared to that in wild-type (WT) mice. Platelets prepared from p38α+/− mice showed impairment of the aggregatory response to a low concentration of U46619, a thromboxane A₂ analogue. Furthermore, platelets prepared from p38α+/− mice and activated by U46619 were poorly bound to fibrinogen compared with those from WT mice. Both the expression and activity of tissue factor induced by FeCl₃ in WT mice were higher than those in p38α+/− mice. These results suggest that p38 plays an important role in thrombus formation by regulating platelet function and tissue factor activity.

• P38
• Mitogen-activated protein kinase
• Platelets
• Thrombosis