Sulfation Patterns in Heparin and Heparan Sulfate: Effects on the Proliferation of Bovine Pulmonary Artery Smooth Muscle Cells

Garg, Hari G.
Yu, Lunyin
Hales, Charles A.
Toida, Toshihiko
Islam, Tasneem
Linhardt, Robert J.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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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.
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.
Biochimical Biophysical Acta, 1639, 225-231
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
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Rensselaer Polytechnic Institute, Troy, NY
Biochimica et Biophysica Acta - Molecular Basis of Disease