Sodium spirulan as a potent inhibitor of arterial smooth muscle cell proliferation in vitro.
Sodium spirulan (Na-SP) is a sulfated polysaccharide with M(r) approximately 220,000 isolated from the blue-green alga Spirulina platensis. The polysaccharide consists of two types of disaccharide repeating units, O-hexuronosyl-rhamnose (aldobiuronic acid) and O-rhamnosyl-3-O-methylrhamnose (acofriose) with sulfate groups, other minor saccharides and sodium ion. Since vascular smooth muscle cell proliferation is a crucial event in the progression of atherosclerosis, we investigated the effect of Na-SP on the proliferation of bovine arterial smooth muscle cells in culture. It was found that Na-SP markedly inhibits the proliferation without nonspecific cell damage. Either replacement of sodium ion with calcium ion or depolymerization of the Na-SP molecule to M(r) approximately 14,700 maintained the inhibitory activity, however, removal of sodium ion or desulfation markedly reduced the activity. Heparin and heparan sulfate also inhibited vascular smooth muscle cell growth but their effect was weaker than that of Na-SP; dextran sulfate, chondroitin sulfate, dermatan sulfate and hyaluronan failed to inhibit the cell growth. The present data suggest that Na-SP is a potent inhibitor of arterial smooth muscle cell proliferation, and the inhibitory effect requires a certain minimum sequence of polysaccharide structure whose molecular conformation is maintained by sodium ion bound to sulfate group.
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan. t-kaji@hokuriku-u.ac.jp
Toshiyuki
T
Kaji
Maiko
M
Okabe
Satomi
S
Shimada
Chika
C
Yamamoto
Yasuyuki
Y
Fujiwara
Jung-Bum
JB
Lee
Toshimitsu
T
Hayashi
D000818:Animals; D001158:Arteries; D002417:Cattle; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D013431:Sulfates / Q000737:chemistry / Q000494:pharmacology*
D011134:Polysaccharides; D013431:Sulfates; C465061:sodium spirulan; D006493:Heparin; D007770:L-Lactate Dehydrogenase