Effect of Very Low Molecular Weight Heparin-Derived Oligosaccharides on Lipoprotein Lipase Release in Rabbits
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Authors
Merchant, Z.M.
Erbe, E.E.
Eddy, W.P.
Patel, D.
Linhardt, Robert J.
Issue Date
1986
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Oligosaccharide fragments of heparin were prepared using flavobacterial heparinase. Following sizing, these oligosaccharide fractions were administered (i.v.) to rabbits and were examined for their ability to release lipoprotein lipase. The decasaccharides (dp = 10, Mr avg = 2,800) were the smallest oligosaccharides which resulted in substantial lipase release. The plasma lipase levels obtained with decasaccharides were comparable to low molecular weight heparin and one-third those obtained when heparin was administered at an equivalent dose. The peak plasma lipase concentration was observed 10 min following heparinization and fell off rapidly over the 60-min time course. The lipase release activity paralleled the in vivo pharmacokinetics of the heparin and decasaccharide sample as determined by monitoring their anti-Factor Xa activity. No activation of purified bovine milk lipoprotein lipase or plasma lipase was detectable at the concentrations studied, indicating that the increase in circulating lipolytic activity was due entirely to release. Lipoprotein lipase accounted for a major portion of the released activity with hepatic triglyceride lipase representing the remainder of the lipolytic activity. The sized decasaccharide sample was characterized with regards to its structure and anticoagulant activity. The decasaccharides exhibited reduced anticoagulant activity possibly making it a better drug candidate in the treatment of atherosclerosis.
Description
Atherosclerosis, 62, 151-158
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Effect of Very Low Molecular Weight Heparin-Derived Oligosaccharides on Lipoprotein Lipase Release in Rabbits, Z.M. Merchant, E.E. Erbe, W.P. Eddy, D. Patel, R.J. Linhardt, Atherosclerosis, 62, 151-158 (1986).