Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator

J Clin Invest. 1986 Jun;77(6):1909-16. doi: 10.1172/JCI112519.

Abstract

Vascular endothelium possesses multiple procoagulant properties, including synthesis and expression of Factor V. We studied the effects of homocysteine on the regulation of endothelial cell Factor V activity. Elevated levels of homocysteine are associated with the congenital thrombotic disorder homocystinuria. Treatment of cultured endothelial cells with 0.5-10 mM homocysteine had no effect on cell morphology, but did increase Factor V activity and prothrombin activation by Factor Xa. A radioimmunoassay for endothelial cell Factor V demonstrated that homocysteine treatment did not increase Factor V antigen levels. 125I-prothrombin was activated by treated endothelial cells and Factor Xa in the presence of thrombin inhibitors. Exogenous 125I-Factor V was cleaved by homocysteine-treated but not control endothelial cells. 125I-Factor V cleavage products distinct from those generated by thrombin and Factor Xa were identified. These data provide evidence for regulation of endothelial cell Factor V activity, and indicate that increased Factor V activity associated with homocysteine-treated vascular endothelium results primarily from induction of an activator of Factor V.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Electrophoresis, Polyacrylamide Gel
  • Endothelial Growth Factors
  • Factor V / metabolism*
  • Factor X / metabolism
  • Factor Xa
  • Growth Substances / pharmacology*
  • Homocysteine / pharmacology*
  • Homocystinuria / complications
  • Humans
  • Molecular Weight
  • Prothrombin / metabolism
  • Thrombosis / complications
  • Umbilical Veins / cytology

Substances

  • Endothelial Growth Factors
  • Growth Substances
  • Homocysteine
  • Factor V
  • Prothrombin
  • Factor X
  • Factor Xa