The effect of phospholipase C on plasma factor VII.
The proposed link between a circulating factor VII-phospholipid complex and the risk of cardiovascular disease (CVD) has stimulated us to investigate the effect of phospholipase C (PLC) on the factor VII (FVII) activity in plasma from healthy individuals. PLC caused a rapid fall in FVII activity which was larger with heparinized than with citrated plasma. EDTA inhibited the PLC effect so emphasizing the involvement of divalent cations. PLC dependent loss of FVII activity varied widely between individuals, showed a highly significant correlation with plasma triglyceride concentrations, and was always greater in post-prandial compared to fasting plasma samples. Experiments using pure recombinant FVIIa and plasma depleted of FVII by adsorption indicated that loss of FVII activity only occurred in the simultaneous presence of absorbed plasma, FVIIa and PLC. Preincubation of PLC with adsorbed plasma before adding FVIIa did not lead to loss of FVII activity. It appears that PLC may act on lipoproteins already bound to FVII, in order to inhibit FVII activity. Other results indicated that competition between different plasma components (lipoproteins) in binding to FVII may govern the extent of the PLC dependent reduction in FVII activity.
Hubbard
A R
AR
Division of Haematology, National Institute for Biological Standards and Control, Potters Bar, Herts.
Parr
L J
LJ
D002951:Citrates / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005167:Factor VII / Q000378:metabolism*; D015942:Factor VIIa / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D010738:Type C Phospholipases / Q000494:pharmacology*
D002951:Citrates; D014280:Triglycerides; D005167:Factor VII; D006493:Heparin; D004492:Edetic Acid; D010738:Type C Phospholipases; D015942:Factor VIIa