PubMed Health⌕ Search

Biomedical subjects

L J Parr

Publications and source records attributed to L J Parr.

8 recordsLinked to original sources

Phospholipase C mediated inhibition of factor VII requires triglyceride-rich lipoproteins.

The reduction of plasma factor VII (FVII) activity by phospholipase C (PLC), in vitro, has been proposed as a possible indication of a risk of cardiovascular disease. The ability of PLC to reduce FVII activity was found to require calcium ions and the presence of triglyceride-rich lipoproteins (e.g. chylomicra and very-low density lipoproteins) rather than high or low density lipoproteins. The PLC-mediated reduction of FVII activity was prevented by pre-incubation of PLC with chylomicra, before adding FVII, and this suggests that PLC may act on triglyceride-rich lipoproteins already bound to FVII in order to reduce FVII activity. At optimal PLC concentration, the extent of the reduction in FVII activity was proportional to the concentration of chylomicra. The detergent, Tween, prevented any loss of FVII activity, in both plasma and purified systems, if it was present at the beginning of the incubation with PLC. Addition of Tween, but not EDTA, after inhibition of FVII activity had occurred, caused a partial restoration of FVII activity. It is concluded that PLC reduces FVII activity by modifying triglyceride-rich lipoproteins to a form which binds to FVII, independently of calcium ions, and which inhibits procoagulant activity. The detection of PLC-sensitive procoagulant activity. The detection of PLC-sensitive FVII activity may therefore have no greater significance than the measurement of plasma triglyceride levels in predicting a risk of cardiovascular disease.

Calcium Chloride↗

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.

Citrates↗