Fucoidan inhibits smooth muscle cell proliferation and reduces mitogen-activated protein kinase activity

Objectives and design: fucoidan has previously been shown to inhibit the pr oliferation of arterial smooth muscle cells both in animal models and in vi tro. However, the mechanisms behind the anti-proliferative effects of this polysulfated polysaccharide are not known in detail. Here, the inhibitory e ffect of fucoidan on mt aortic smooth muscle cell proliferation was examine d and compared with the effects of heparin after stimulation with fetal cal f serum, platelet-derived growth factor BE, basic fibroblast growth factor, heparin-binding epidermal growth factor, and angiotensin II. Materials and methods: the cultures were analysed with respect to cell prol iferation and DNA synthesis by cell counting and measurement of H-3-thymidi ne incorporation. Phosphorylation of mitogen-activated protein kinase and n uclear translocation of phosphorylated mitogen-activated protein kinase wer e studied by immunoblotting and immunocytochemistry. Results: fucoidan was shown to be a move potent inhibitor of smooth muscle cell proliferation than heparin. Fucoidan also reduced growth factor-induce d activation of mitogen-activated protein kinase and prevented nuclear tran slocation of phosphorylated mitogen-activated protein kinase. Conclusion:fucoidan is a more potent anti-proliferative polysulphated polys accharide than heparin and may mediate its effects through inhibition of th e mitogen-activated protein kinase pathway in a similar manner as heparin.