title: Fucoidan inhibits smooth muscle cell proliferation and reduces mitogen-activated protein kinase activity.
abstract: OBJECTIVE
  fucoidan has previously been shown to inhibit the proliferation of arterial smooth muscle cells both in animal models and in vitro. However, the mechanisms behind the anti-proliferative effects of this polysulfated polysaccharide are not known in detail. Here, the inhibitory effect of fucoidan on rat aortic smooth muscle cell proliferation was examined and compared with the effects of heparin after stimulation with fetal calf serum, platelet-derived growth factor BB, basic fibroblast growth factor, heparin-binding epidermal growth factor, and angiotensin II.
  
  
  METHODS
  the cultures were analysed with respect to cell proliferation and DNA synthesis by cell counting and measurement of(3)H-thymidine incorporation. Phosphorylation of mitogen-activated protein kinase and nuclear translocation of phosphorylated mitogen-activated protein kinase were studied by immunoblotting and immunocytochemistry.
  
  
  RESULTS
  fucoidan was shown to be a more potent inhibitor of smooth muscle cell proliferation than heparin. Fucoidan also reduced growth factor-induced activation of mitogen-activated protein kinase and prevented nuclear translocation of phosphorylated mitogen-activated protein kinase.
  
  
  CONCLUSIONS
  fucoidan is a more potent anti-proliferative polysulphated polysaccharide than heparin and may mediate its effects through inhibition of the mitogen-activated protein kinase pathway in a similar manner as heparin.
authors: Department of Surgical Sciences, Division of Vascular Surgery, SE-171 76 Stockholm, Sweden.
authors: P
authors: P
authors: Religa
authors: M
authors: M
authors: Kazi
authors: J
authors: J
authors: Thyberg
authors: Z
authors: Z
authors: Gaciong
authors: J
authors: J
authors: Swedenborg
authors: U
authors: U
authors: Hedin
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000925:Anticoagulants; D010982:Platelet-Derived Growth Factor; D011134:Polysaccharides; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; D006493:Heparin; D004247:DNA; C007789:fucoidan; D020928:Mitogen-Activated Protein Kinases