Plasma lipoproteins enhance tissue factor-independent factor VII activation

The effect of plasma lipoprotein fractions (large very-low-density lipoprot ein, small very-low-density lipoprotein, intermediate-density lipoprotein, and low-density lipoprotein) on initiation of blood coagulation by supporti ng factor VII activation or by stimulating monocytes to express tissue fact or was investigated in vitro. Endotoxin-free preparations of lipoprotein fr actions did not induce functional tissue factor in monocytes, whereas all l ipoprotein fractions enhanced tissue factor-independent activation of facto r VII by factor Xa and by factors Xa/Va. In contrast, no or only slight enh ancement of factor IXa-, factor IXa/VIIIa-, factor XIa-, or thrombin-mediat ed 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 V II activation. When the data were normalized for apolipoprotein B-100 conte nt, differences remained between lipoprotein fractions. In contrast, when p hospholipid content was used for normalization, differences between lipopro tein fractions in factor Xa- and factor Xa/Va-mediated factor VII activatio n disappeared, indicating that phospholipids were involved in factor VII ac tivation. This was supported by enhancement of factor Xa-mediated factor VI I activation by synthetic phospholipid vesicles containing negatively charg ed phospholipids.