The Antimitogenic Action of the Sulphated Polysaccharide Fucoidan Differs from Heparin in Human Vascular Smooth Muscle Cells

Mahendra K. Patel; Barbara Mulloy; Karen L. Gallagher; Leisha O’Brien; Alun D. Hughes

doi:10.1055/s-0037-1612958

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 87(01): 149-154
DOI: 10.1055/s-0037-1612958

Review Article

Schattauer GmbH

The Antimitogenic Action of the Sulphated Polysaccharide Fucoidan Differs from Heparin in Human Vascular Smooth Muscle Cells

Mahendra K. Patel

¹Clinical Pharmacology, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, St. Mary’s Campus, London, UK

,

Barbara Mulloy

¹Clinical Pharmacology, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, St. Mary’s Campus, London, UK

²Laboratory for Molecular Structure, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts., UK

,

Karen L. Gallagher

¹Clinical Pharmacology, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, St. Mary’s Campus, London, UK

,

Leisha O’Brien

¹Clinical Pharmacology, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, St. Mary’s Campus, London, UK

,

Alun D. Hughes

¹Clinical Pharmacology, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, St. Mary’s Campus, London, UK

› Institutsangaben

Abstract

Summary

The sulphated polysaccharides fucoidan and heparin both inhibit vascular smooth muscle cell (VSMC) proliferation. In this study we compared their actions on mitogenesis and ERK1/ERK2 activation in human VSMC. Although they displaced cell surface [3H]-heparin binding with similar affinity, they exerted clearly distinguishable actions. Fucoidan potently inhibited DNA synthesis stimulated by foetal calf serum, PDGF-BB and thrombospondin-1. Heparin inhibited the mitogenic action of serum and thrombospondin-1 (though less potently than fucoidan), but failed to inhibit PDGF-BB-induced DNA synthesis. In parallel studies, fucoidan, but not heparin, inhibited ERK1/ERK2 activation by PDGF-BB. Moreover, fucoidan inhibited serum-induced mitogenesis in “heparin resistant” VSMC, which are refractory to heparin’s antimitogenic action. In summary, the structurally different polysaccharides, heparin, fucoidan (and fucans) have distinguishable effects on mitogenesis and ERK1/ERK2 activation, suggesting that different mechanism(s) mediate these actions. The potent antimitogenic action of fucoidan and its efficacy in heparin resistant VSMC emphasise the need to further investigate its mechanism of action in human VSMC and suggest this agent could have therapeutic potential.

Keywords

Fucoidan - heparin - human vascular smooth muscle - DNA synthesis - ERK1/ERK2 activation

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