Role of p38 mitogen-activated protein kinase in thrombus formation.
The present study was designed to elucidate the role of p38 mitogen-activated protein kinase (p38) in thrombus formation. We used p38alpha heterozygous (p38alpha+/-) 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 p38alpha+/- mice was prolonged compared to that in wild-type (WT) mice. Platelets prepared from p38alpha+/- mice showed impairment of the aggregatory response to a low concentration of U46619, a thromboxane A2 analogue. Furthermore, platelets prepared from p38alpha+/- 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 p38alpha+/- mice. These results suggest that p38 plays an important role in thrombus formation by regulating platelet function and tissue factor activity.
Sakurai
Kanako
K
Department of Biochemistry and Molecular Pharmacology and Chiba University Graduate School of Medicine, Chiba, Japan.
Matsuo
Yuji
Y
Sudo
Tatsuhiko
T
Takuwa
Yoh
Y
Kimura
Sadao
S
Kasuya
Yoshitoshi
Y
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000483:Alleles; D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D002712:Chlorides; D005290:Ferric Compounds / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010920:Placenta / Q000378:metabolism; D010973:Platelet Adhesiveness; D011485:Protein Binding; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism*; D013928:Thromboxane A2 / Q000031:analogs & derivatives; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*
D002712:Chlorides; D005290:Ferric Compounds; D020033:Protein Isoforms; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005340:Fibrinogen; D013925:Thromboplastin; D048051:p38 Mitogen-Activated Protein Kinases; C024555:ferric chloride