Effects of middle molecular weight fucoidans on in vitro and ex vivo angiogenesis of endothelial cells

Native fucoidan, sulfated L-fucose polymer isolated from marine brown algae, has diverse biological activities including anticoagulant, anti-angiogenic and anti-tumor effects. Its anti-angiogenic effect is of interest and the mechanisms have been studied. However, recently, proangiogenic effect of low molecular weight (LMW) fucoidans has been demonstrated. To clarify the opposite effects of fucoidan and LMW fucoidans, it is necessary to address the relationship between the molecular size and the effect on angiogenesis. In this study, the effects of middle molecular weight (MMW) fucoidans (15-30 kDa) on human umbilical vein endothelial cell functions were examined. Fucoidan (30 kDa) had similar effects to native fucoidan; inhibition of HUVEC tube formation and angiogenesis in an ex vivo model, although their effects were weaker than native fucoidan. On the other hand, 15-20 kDa fucoidan enhanced HUVEC migration, but did not inhibit HUVEC tube formation. Thus, 15-20 kDa fucoidan would have proangiogenic effect on angiogenesis. These results elucidate that 20-30 kDa would be a critical point to characterize the role of fucoidans on angiogenesis.