Therapeutic effect of fucoidan‐stimulated endothelial colony‐forming cells in peripheral ischemia

Abstract

Summary. Background: Fucoidan, an antithrombotic polysaccharide, can induce endothelial colony-forming cells (ECFC) to adopt an angiogenic phenotype in vitro. Objectives: We evaluated the effect of fucoidan on vasculogenesis induced by ECFC in vivo. Methods: We used a murine hindlimb ischemia model to probe the synergic role of fucoidan-treatment and ECFC infusion during tissue repair. Results: We found that exposure of ECFC to fucoidan prior to their intravenous injection improved residual muscle blood flow and increased collateral vessel formation. Necrosis of ischemic tissue was significantly reduced on day 14, to 12.1% of the gastronecmius cross-sectional surface area compared with 40.1% in animals injected with untreated-ECFC. ECFC stimulation with fucoidan caused a rapid increase in cell adhesion to activated endothelium in flow conditions, and enhanced transendothelial extravasation. Fucoidan-stimulated ECFC were resistant to shear stresses of up to 21 dyn cm ) had significantly lower mean serum creatine phosphokinase (CPK) activity than control animals. This CPK reduction was correlated with muscle preservation against necrosis (P < 0.001). Conclusions:Fucoidan greatly increases ECFC-mediated angiogenesis in vivo. Its angiogenic effect would be due in part to its transportation to the ischemic site and its release after displacement by proteoglycans present in the extracellular matrix. The use of ECFC and fucoidan together, will be an efficient angiogenesis strategy to provide therapeutic neovascularization.

Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells

“…Animal care conformed to French guidelines (Services Vétérinaires de la Santé et de la Production Animale, Paris, France), and experiments were performed in keeping with the guidelines of the Paris-Descartes University Institutional Committee on Animal Care and Use (C75.06.02). The mice underwent surgery to induce unilateral hind limb ischemia as previously described [23,24]. Briefly, animals were anesthetized by inhalation of isoflurane.…”

Prospects for the therapeutic application of sulfated polysaccharides of brown algae in diseases of the cardiovascular system: review

“…Fucoidan may bind proangiogenic growth factors and confer a stable, receptor-compatible conformational change upon growth factors, which might increase their affinity for their receptors and improve the angiogenesis process (Sarlon et al 2012). Competitive binding of fucoidan to SDF-1 promotes its release from the surface of endothelial cells and the extracellular matrix in the bone marrow and other tissues, which results in the mobilization of bone-marrow stem cells (Sweeney et al 2002).…”

“…This latter effect was correlated with upregulation of the cell-surface a6 integrin subunit of the laminin receptor and the authors suggest that ex vivo fucoidan might precondition EPC and lead to increased neovascularization when injected into ischemic tissues. Sarlon et al (2012) showed that fucoidan greatly increases ECFCmediated angiogenesis in vivo. ECFC stimulation with fucoidan caused a rapid increase in cell adhesion to activated endothelium in flow conditions, and enhanced transendothelial extravasation.…”

“…The pleiotropic action of fucoidans is associated with structural features. It is believed that certain moieties of polysulfated chain fucoidans can serve as mimetics of natural ligand protein receptors -glycosaminoglycans (GAG) including heparan sulfate (Krylov et al 2011;Sarlon et al 2012;Wijesinghe & Jeon 2012;Marinval et al 2015). The binding of GAG to various proteins in tissues leads to in post-translational modifications, which determine cell behavior, cell migration, proliferation, differentiation, inflammation and angiogenesis (Turnbull et al 2001).…”

Downregulation of Microparticle Release and Pro-Inflammatory Properties of Activated Human Polymorphonuclear Neutrophils by LMW Fucoidan

“…A low-molecular-weight fucoidan (LMW-Fuc) extracted from the brown algae Asco­phyllum nodosum was described to present negligible anticoagulant activity, but potent antithrombotic and pro-angiogenic effects, being suggested as potential neovascularization agent [14, 15]. Nevertheless, no studies have addressed the specific effects of LMW-Fuc on the inflammatory response.…”