Sulfation Patterns in Heparin and Heparan Sulfate: Effects on the Proliferation of Bovine Pulmonary Artery Smooth Muscle Cells
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Authors
Garg, Hari G.
Yu, Lunyin
Hales, Charles A.
Toida, Toshihiko
Islam, Tasneem
Linhardt, Robert J.
Issue Date
2003-11-20
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Heparin's (HP's) antiproliferative effect on smooth muscle cells is potentially important in defining new approaches to treat pulmonary hypertension. The commercially available HP and heparan sulfate (HS) are structurally heterogenous polymers. In order to examine which sulfonate groups are required for endogenous antiproliferative activity, we prepared the following six chemically modified porcine mucosal HP and HS, which fell into three groups. One group consisted of fully O-sulfonated-N-acetylated, the second group consisted of de-N-sulfonated and re-N-acetylated, and the third group consisted of 6-O-desulfonated HP and HS derivatives. These six preparations were assayed for their antiproliferative potency on bovine pulmonary artery smooth muscle cells. The results of this assay show that (a) over-O-sulfonation of both HP and HS increases antiproliferative activity, (b) substitution of hexosamine with N-acetyl diminishes antiproliferative activity in both HP and HS, and (c) 6-O-desulfonation of HP and HS diminishes antiproliferative potency. Surprisingly, the type of uronic acid residue present at a given level of sulfation is unimportant for antiproliferative potency. In conclusion, only the level of O- and N-sulfo group substitution correlates well with HP and HS antiproliferative activity.
Description
Biochimical Biophysical Acta, 1639, 225-231
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
Sulfation Patterns in Heparin and Heparan Sulfate: Effects on the Proliferation of Bovine Pulmonary Artery Smooth Muscle Cells, H. G. Garg, L. Yu, C.A. Hales, T. Toida, T. Islam, R. J. Linhardt, Biochimical Biophysical Acta, 1639, 225-231, 2003.
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ISSN
9254439