Heparin Oligosaccharide Sequence and Size Essential for Inhibition of Pulmonary Artery Smooth Muscle Cell Proliferation
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Authors
Garg, Hari G.
Cindhuchao, Naiyaratana
Quinn, Deborah A.
Hales, Charles A.
Thanawiroon, Charuwan
Capila, Ishan
Linhardt, Robert J.
Issue Date
2002-11-19
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Heparin has a wide range of important biological activities including inhibition of pulmonary artery smooth muscle cell proliferation. To determine the minimum size of the heparin glycosaminoglycan chain essential for antiproliferative activity, porcine intestinal mucosal heparin was partially depolymerized with heparinase and fractionated to give oligosaccharides of different sizes. The structure of these oligosaccharides was fully characterized by 1D and 2D 1H NMR spectroscopy. These oligosaccharides were assayed for antiproliferative effects on cultured bovine pulmonary artery smooth muscle cells (PASMCs). The tetrasaccharide (4-mer) exhibited no heparin-like activity. Decasaccharides (10-mers) and dodecasaccharides (12-mers) displayed a reduced level of activity when compared to full-length heparin. Little effect on activity was observed in deca- and dodecasaccharides with one less 2-O-sulfo group. The 14-, 16-, and 18-mers showed comparable growth-inhibition effects on PAMSC as porcine intestinal mucosal heparin. These data suggest that a 14-mer is the minimum size of oligosaccharide that is essential for full heparin-like antiproliferative activity. Since the 14- to 18-mers have no 3-O-sulfo groups in their glucosamine residues, their full activity confirms that these 3-O-sulfonated glucosamine residues, which are required for heparin's anticoagulant activity, are not an essential requirement for antiproliferative activity.
Description
Carbohydrate Research, 337, 2359-2364
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
Heparin Oligosaccharide Sequence and Size Essential for Inhibition of Pulmonary Artery Smooth Muscle Cell Proliferation, H.G. Garg, N. Cindhuchao, C. A. Hales, C. Thanawiroon, I. Capila, R. J. Linhardt, Carbohydrate Research, 337, 2359-2364, 2002.
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Volume
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DOI
ISSN
86215