Fucoidan is a non-anticoagulant inhibitor of intimal hyperplasia.
We previously reported that heparin inhibits the proliferation of fibroblasts and vascular smooth muscle cells (SMC), in part, by binding to and increasing the antiproliferative activity of transforming growth factor-beta 1 (TGF-beta 1). We now report that certain other polyanions which are structurally distinct from heparin, such as fucoidan and polyinosinic acid, are more avid ligands for TGF-beta 1 and more potent antiproliferative agents than heparin. Fucoidan possessed more potent antiproliferative activity than heparin against rat and bovine aortic SMC in vitro, though possessing much lower anticoagulant activity than heparin. Furthermore, fucoidan suppressed in vivo intimal hyperplasia when continuously infused into rats subjected to balloon-catheter injury. Unlike heparin, which also suppressed intimal hyperplasia, fucoidan did not cause systemic anticoagulation. Thus, fucoidan may be useful as a non-anticoagulant inhibitor of post-angioplasty intimal hyperplasia.
McCaffrey
T A
TA
Department of Medicine, Cornell University Medical College, New York, NY 10021.
Falcone
D J
DJ
Borth
W
W
Brayton
C F
CF
Weksler
B B
BB
D000818:Animals; D000838:Anions; D001011:Aorta / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology*; D006965:Hyperplasia; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000838:Anions; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D006493:Heparin; C007789:fucoidan