Vitamin K-dependent proteins bind to very low-density lipoproteins.
It has been demonstrated that the surface of large VLDL Sf 100-400 can bind both prothrombin and Factor X(Xa) and that on VLDL Factor Xa can convert prothrombin to thrombin, which degrades apo B and apo E. It has been reported also that the VLDL kinetically supports the conversion of prothrombin to thrombin. The binding of vitamin K-dependent proteins to phospholipid is partially Ca2+-dependent and probably involves their Gla residues. The complex of VLDL, prothrombin, Factor Xa, and Ca2+ lacks only Factor Va, a lipid associating, non-Gla residue containing 330 kd protein, to complete the "prothrombinase complex." Factor V (Va) is found at very low concentrations in the circulation, but is localized on platelets, monocytes, and the endothelium. VLDL can bind both to monocytes and to the endothelium, for example, through both receptor and non-receptor pathways. When carrying this complement of the prothrombinase complex, this subpopulation of VLDL, in the presence of Factor Va on cell surfaces, could conceivably upset the local balance of pro- and anticoagulant activities. Thus, directly or indirectly the increased triglyceride levels, reflected in increased VLDL in patients, may alter this balance, and thereby produce a "hypercoagulable state." This is a simplistic view of the potential role of VLDL in the interplay of cells, coagulation proteins, and the regulatory systems involved in vivo. To realize the degree of complexity that we may need to address, we need only look at the work of Booyse et al in this issue of Seminars, in which they demonstrate that hypertriglyceridemic VLDL, in contrast to normal VLDL, do not support the early release of t-PA from endothelial cells, an antifibrinolytic event.(ABSTRACT TRUNCATED AT 250 WORDS)
D002135:Calcium-Binding Proteins / Q000097:blood*; D005170:Factor X / Q000378:metabolism; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood*; D011485:Protein Binding; D011516:Prothrombin / Q000378:metabolism; D014812:Vitamin K / Q000097:blood*
D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D008079:Lipoproteins, VLDL; D014812:Vitamin K; D011516:Prothrombin; D005170:Factor X