Plasma lipoproteins enhance tissue factor-independent factor VII activation.
The effect of plasma lipoprotein fractions (large very-low-density lipoprotein, small very-low-density lipoprotein, intermediate-density lipoprotein, and low-density lipoprotein) on initiation of blood coagulation by supporting factor VII activation or by stimulating monocytes to express tissue factor was investigated in vitro. Endotoxin-free preparations of lipoprotein fractions did not induce functional tissue factor in monocytes, whereas all lipoprotein fractions enhanced tissue factor-independent activation of factor VII by factor Xa and by factors Xa/Va. In contrast, no or only slight enhancement of factor IXa-, factor IXa/VIIIa-, factor XIa-, or thrombin-mediated factor VII activation was observed. The effect of small very-low-density lipoprotein was less than that of large very-low-density lipoprotein, and intermediate-density and low-density lipoproteins caused an even lower but still significant increase of factor Xa- and factor Xa/Va-mediated factor VII activation. When the data were normalized for apolipoprotein B-100 content, differences remained between lipoprotein fractions. In contrast, when phospholipid content was used for normalization, differences between lipoprotein fractions in factor Xa- and factor Xa/Va-mediated factor VII activation disappeared, indicating that phospholipids were involved in factor VII activation. This was supported by enhancement of factor Xa-mediated factor VII activation by synthetic phospholipid vesicles containing negatively charged phospholipids.
Kjalke
M
M
Tissue Factor/Factor VII Research, Novo Nordisk, Målov, Denmark. mkja@novo.dk
Silveira
A
A
Hamsten
A
A
Hedner
U
U
Ezban
M
M
D001777:Blood Coagulation; D002784:Cholesterol / Q000097:blood / Q000494:pharmacology*; D005167:Factor VII / Q000378:metabolism*; D005170:Factor X / Q000378:metabolism; D015945:Factor XIa / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000097:blood / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D013925:Thromboplastin / Q000378:metabolism*
D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C030104:lipoprotein cholesterol; D005167:Factor VII; D005170:Factor X; D013925:Thromboplastin; D002784:Cholesterol; D015945:Factor XIa; D015951:Factor Xa