Plasma glucosylceramide deficiency as risk factor for thrombosis and modulator of anticoagulant protein C

作者: John H. Griffin , Hiroshi Deguchi , Jose Fernandez

DOI:

关键词:

摘要: The present invention has determined that exogenously added glycosylceramide (GlcCer) and other neutral glycolipids such as the homologous Glc-containing globotriaosylceramide (Gb3Cer), dose-dependently prolonged clotting times of normal plasma in presence but not absence APC:protein S, indicating GlcCer or Gb3Cer can enhance protein C pathway anticoagulant activity. In studies using purified proteins, inactivation factor Va by S was enhanced alone GlcCer, globotriaosylceramide, lactosylceramide, galactosylceramide multicomponent vesicles containing phosphatidylserine phosphatidylcholine. Thus, provides Gb3Cer, cofactors contribute to antithrombotic activity pathway. also a deficiency is risk for thrombosis. Methods are provided determine individuals at thrombosis, methods treatment well screening factors from glycolipids.

参考文章(21)
A M Scanu, A M Scanu, G Dawson, G Dawson, A W Kruski, A W Kruski, A W Kruski, Distribution of glycosphingolipids in the serum lipoproteins of normal human subjects and patients with hypo- and hyperlipidemias. Journal of Lipid Research. ,vol. 17, pp. 125- 131 ,(1976) , 10.1016/S0022-2275(20)36996-0
Donald J. Phillips, Judith S. Greengard, Jose A. Fernandez, Maria Ribeiro, Bruce L. Evatt, John H. Griffin, W. Craig Hooper, Protein S, an antithrombotic factor, is synthesized and released by neural tumor cells. Journal of Neurochemistry. ,vol. 61, pp. 344- 347 ,(1993) , 10.1111/J.1471-4159.1993.TB03574.X
Hiroshi Deguchi, José A. Fernández, John H. Griffin, Neutral Glycosphingolipid-dependent Inactivation of Coagulation Factor Va by Activated Protein C and Protein S Journal of Biological Chemistry. ,vol. 277, pp. 8861- 8865 ,(2002) , 10.1074/JBC.M110252200
John H. Griffin, Kazuhisa Kojima, Carole L. Banka, Linda K. Curtiss, José A. Fernández, High-density lipoprotein enhancement of anticoagulant activities of plasma protein S and activated protein C Journal of Clinical Investigation. ,vol. 103, pp. 219- 227 ,(1999) , 10.1172/JCI5006
José A Fernández, Kazuhisa Kojima, Jari Petäjä, Tilman M Hackeng, John H Griffin, Cardiolipin enhances protein C pathway anticoagulant activity. Blood Cells Molecules and Diseases. ,vol. 26, pp. 115- 123 ,(2000) , 10.1006/BCMD.2000.0285