Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme

Abstract

This study compares a low-Mr heparin preparation with conventional heparin with respect to its interaction with lipoprotein lipase (LPL) in vitro and its effects on the enzyme in vivo. Both heparin preparations were polydisperse in binding to LPL, but on average the low-Mr preparation showed lower affinity. Thus both conventional and low-Mr heparin bound quantitatively to immobilized LPL, and were eluted as broad peaks when a salt gradient was applied, but the peak for low-Mr heparin was shifted towards lower salt concentrations. To displace LPL from immobilized heparin a higher concentration of low-Mr than of conventional heparin was needed. Injection of the low-Mr heparin into intact rats resulted in lower plasma LPL activity than did injection of an equal mass of conventional heparin, but when the liver was excluded from the circulation both heparin preparations resulted in similar plasma LPL activities. In perfused rat hearts, low-Mr heparin had at least the same effect on the release of LPL activity as did conventional heparin. In perfused livers, on the other hand, low-Mr heparin was less effective than conventional heparin in preventing the rapid uptake of exogenous labelled LPL. Hence the apparently lower average affinity of low-Mr heparin for LPL does not result in a demonstrably lower potency to release the enzyme from endothelial binding sites in peripheral tissues, but does result in a substantially decreased effect on the hepatic clearance of the enzyme.

Announcement

“…We can hypothesize that Lp(a) may be re leased from the endothelial vascular surface. This hypothesis is supported by the observa tion that Lp(a) is bound to glycosaminoglycans and to plasminogen receptor on the endothelial surface [4] and that LMWH can release lipoprotein lipase, anchored to the vascular endothelium through glycosantinoglyeans, into the circulation [4], A similar mechanism might be involved in the release of Lp(a) into the bloodstream after Nadroparin administration.…”

Biphasic effects of low-molecular-weight and conventional heparins on chylomicron clearance in rats.

“…18 The present study was designed to test if and for how long this happens with clinically relevant doses of heparin. The results showed that the period of decreased catabolism is not unique to LMWH.…”

Isolation and Characterization of Low Sulfated Heparan Sulfate Sequences with Affinity for Lipoprotein Lipase

“…After gentle mixing with the gel at 4°C overnight, any remaining activated groups were blocked by cold 5% (v/v) ethanolamine in 0.1 M NaHCO 3 , pH 9.0, 0.5 M NaCl, for 4 h. After wash, the gel was stored in 10 mM BisTris, pH 6.5, 0.1 M NaCl, containing 1 mg of heparin/ml to protect the enzyme from inactivation. Previous studies have shown that, under the conditions used, the gel contains ϳ1 mg of LPL protein/ml, and the binding properties remain essentially unchanged for 2-3 weeks on storage at 4°C (30,31). The LPL-Sepharose beads were therefore used within 2 weeks after manufacturing, and all column runs were performed at 4°C.…”