Plasma cholesteryl ester transfer protein and blood coagulability.
Dyslipoproteinemia involving low levels of high density lipoprotein (HDL) is linked to venous thrombosis in young male adults and to recurrence of venous thrombosis in patients who have experienced a previous unprovoked venous thrombosis episode. Plasma cholesteryl ester transfer protein (CETP) modulates HDL metabolism and some lipoproteins can affect blood coagulation reactions with either procoagulant or anticoagulant effects. Hence, we evaluated relationships between the mass of CETP and blood coagulability in plasma samples from 39 normal healthy adults. For clotting initiated by dilute tissue factor or factor XIa, clotting times significantly correlated with CETP antigen levels. Thus, coagulation initiated by either the extrinsic or intrinsic coagulation pathway is positively correlated with CETP plasma levels. When added to plasma, a recombinant CETP preparation dose-dependently shortened factor Xa-1-stage clotting times, showing that it augmented procoagulant activity in plasma. In reaction mixtures containing purified factors Xa and Va and prothrombin, the recombinant CETP preparation dose-dependently increased prothrombin activation, suggesting it specifically enhances prothrombinase activity. Thus, our data highlight a previously unknown positive relationship between CETP plasma levels and blood coagulability that might relate to risks for thrombotic events.
Dept. of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Hiroshi
H
Deguchi
José A
JA
Fernández
John H
JH
Griffin
D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015943:Factor Va / Q000378:metabolism; D015945:Factor XIa / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000378:metabolism; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013925:Thromboplastin / Q000378:metabolism
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D011994:Recombinant Proteins; D015943:Factor Va; D011516:Prothrombin; D013925:Thromboplastin; D015945:Factor XIa; D015951:Factor Xa