Significance of the 2-O-sulfo group of L-iduronic acid residues in heparin on the growth inhibition of bovine pulmonary artery smooth muscle cells.
Heparin inhibits the growth of several cell types in vitro, including bovine pulmonary artery smooth muscle cells (BPASMCs). To understand more about the heparin structure required for endogenous activity, chemically modified derivatives of native heparin and glycol-split heparin, namely, 2-O-desulfonated iduronic/glucuronic acid residues in heparin, and 2-O-desulfonated iduronic residues in glycol-split heparin were prepared. These were assayed for their antiproliferative potency on cultured BPASMCs. All of the 2-O-desulfonated heparin derivatives had significantly decreased less antiproliferative activity on BPASMCs. These results suggest that the 2-O-sulfo group of iduronic acid residues in heparin's major sequence is essential for the antiproliferative properties of heparin. The size of heparin does not affect the growth-inhibitory properties of heparin on BPASMCs at the three dose levels examined.
Garg
Hari G
HG
Department of Medicine, Pulmonary/Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. hgarg@partners.org
Mrabat
Hicham
H
Yu
Lunyin
L
Freeman
Craig
C
Li
Boyangzi
B
Zhang
Fuming
F
Linhardt
Robert J
RJ
Hales
Charles A
CA
D000818:Animals; D002240:Carbohydrate Sequence; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006493:Heparin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D007067:Iduronic Acid / Q000737:chemistry*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D011651:Pulmonary Artery / Q000166:cytology*; D013455:Sulfur / Q000737:chemistry*
D007067:Iduronic Acid; D013455:Sulfur; D006493:Heparin