Inhibition of Plasma Coagulation through Interaction between Oxidized Low-Density Lipoprotein and Blood Coagulation Factor VIII(Biochemistry/Molecular Biology)

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概要

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• Oxidatively modified low-density lipoprotein (OxLDL) is present in atherosclerotic lesions and has been proposed to play an important role in atherogenesis. Thrombosis is the major mechanism underlying acute complications of atherosclerosis. In the present study, we analyzed the interaction between OxLDL and blood coagulation factors, which are involved in the blood coagulation pathway. We investigated the effect of OxLDL on plasma coagulation by measuring prothrombin time (PT) as a parameter of the extrinsic pathway of blood coagulation and activated partial thromboplastin time (APTT) as a parameter of the intrinsic pathway of blood coagulation following the addition of OxLDL to plasma. OxLDL, but not native LDL, caused prolongation of APTT in a dose- and oxidation time-dependent manner. In addition, the oxidatively modified product of acetylated LDL (AcLDL), but not AcLDL, also caused prolongation of APTT. The inhibition of lysophosphatidylcholine production in OxLDL by phenylmethylsulfonyl fluoride or Pefabloc pretreatment of LDL resulted in a prolongation of APTT, which was equivalent to the effect of OxLDL. Moreover, OxLDL significantly inhibited blood coagulation factor VIII, IX, and XI activity. Furthermore, we demonstrated that recombinant factor VIII binds to OxLDL and that factor VIII associated with OxLDL is detected in the incubation mixture of OxLDL and plasma. These results indicate that the binding of factor VIII to OxLDL affects the intrinsic pathway of the blood coagulation cascade. The present study suggests that the interaction between OxLDL and factor VIII may provide important information on the initiation and progression of atherosclerosis.

• 公益社団法人日本薬学会の論文
• 2005-06-01

著者

• Kumagai Takeshi

  Tohoku Pharmaceutical University

• Kumagai Takeshi

  Department Of Environmental Health Science Tohoku Pharmaceutical University

• Kumagai Takeshi

  東北薬科大学 環境衛生学

• Kumagai T

  Tohoku Pharmaceutical Univ. Sendai Jpn

• YOKOTA Katsushi

  First Department of Hygienic Chemistry, Tohoku Pharmaceutical University

• 蝦名 敬一

  東北薬大・環境衛生

• TSUTSUMI Hiromu

  Department of Environmental Health Science, Tohoku Pharmaceutical University

• YOKOTA Katsushi

  Department of Environmental Health Science, Tohoku Pharmaceutical University

• TSUTSUMI Hiromu

  First Department of Hygienic Chemistry, Tohoku Pharmaceutical University

• KUMAGAI Takeshi

  First Department of Hygienic Chemistry, Tohoku Pharmaceutical University

• EBINA Keiichi

  First Department of Hygienic Chemistry, Tohoku Pharmaceutical University

• HOSHI Yukari

  First Department of Hygienic Chemistry, Tohoku Pharmaceutical University

• Hoshi Yukari

  First Department Of Hygienic Chemistry Tohoku Pharmaceutical University

• Ebina Keiichi

  Department Of Environmental Health Science Tohoku Pharmaceutical University

• Kataoka Yumi

  Department Of Environmental Health Science Tohoku Pharmaceutical University

• Yokota Katsushi

  First Department Of Hygienic Chemistry Tohoku College Of Pharmacy

• Tsutsumi Hiromu

  Department Of Environmental Health Science Tohoku Pharmaceutical University

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