Effect of fully sulfated glycosaminoglycans on pulmonary artery smooth muscle cell proliferation.
Fully sulfated heparin and other glycosaminoglycans, namely heparan, chondroitin, and dermatan sulfates, and hyaluronan have been prepared by using sulfur trioxide under mild chemical conditions. All these derivatives were assayed for antiproliferative activity on cultured bovine pulmonary artery smooth muscle cells (BPASMCs). No appreciable difference was found between heparin and fully sulfated heparin. Chondroitin and dermatan sulfates actually stimulated BPASMCs growth but full sulfonation made them strongly antiproliferative. Native hyaluronan was not antiproliferative but became strongly so after sulfonation. Neither acharan sulfate nor N-sulfoacharan sulfate had any antiproliferative activity. This suggests that O-sulfonation of the polysaccharide is critical for antiproliferative activity, whereas N-sulfonation of glucosamine residues is not.
Garg
H G
HG
Pulmonary/Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. hgarg@partners.org
Joseph
P A
PA
Thompson
B T
BT
Hales
C A
CA
Toida
T
T
Imanari
T
T
Capila
I
I
Linhardt
R J
RJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D002417:Cattle; D002478:Cells, Cultured; D006025:Glycosaminoglycans / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011651:Pulmonary Artery / Q000166:cytology*; D017421:Sequence Analysis
D000970:Antineoplastic Agents; D006025:Glycosaminoglycans; C013786:A73025