The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P‐ and <scp>l</scp>‐selectin function <i>in vivo</i>

Thorlacius,; Vollmar,; Seyfert,; Vestweber,; Menger,

doi:10.1046/j.1365-2362.2000.00704.x

Cited by 55 publications

(47 citation statements)

References 35 publications

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“…Fucoidan interferes with selectins which could inhibit binding of platelets and leukocytes to endothelial cells and thus prevent thrombosis. However, as previously reported by Thorlacius et al [20] with a higher molecular weight fucoidan, the antithrombotic effect of LMWF was not mediated by inhibition of P-selectin, as we observed no significant difference in P-selectin expression among the 3 groups of animals [20]. Moreover, we ruled out a major contribution of leukocytes in our model, as leukocytes were detected in very small numbers in the media of the arteries in the 3 groups.…”

Section: Discussionsupporting

confidence: 69%

Effect of Low Molecular Weight Fucoidan and Low Molecular Weight Heparin in a Rabbit Model of Arterial Thrombosis

Durand¹,

Helley

Zen

et al. 2008

J Vasc Res

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Background: Therapeutic use of unfractionated heparin and low molecular weight heparins (LMWHs) is limited by hemorrhagic adverse effects. We compared the antithrombotic effect of LMW fucoidan (LMWF) and LMWH in an experimental model. Methods: Thrombosis was induced in femoral arteries of male New Zealand White rabbits by in situ induction of endothelial apoptosis with staurosporine (10^–5M for 30 min). Starting the day before apoptosis induction, the animals received subcutaneous LMWF (15 mg/kg), LMWH (enoxaparin 2.5 mg/kg) or saline solution (control group) twice a day for 4 days. Results: The degrees of apoptosis and endothelial denudation were similar in the 3 groups. The thrombotic score was significantly lower in the LMWF group than in the LMWH and control groups (p = 0.01). Tissue factor expression was significantly lower in the LMWF group than in the control and LMWH groups (p = 0.01). The plasma concentration of tissue factor pathway inhibitor was significantly increased after LMWF injection (137 ± 28 vs. 102 ± 17; p = 0.01), whereas no change was observed after LMWH treatment. LMWF did not prolong the bleeding time or decrease platelet aggregation. Conclusions: LMWF appeared to be more effective than LMWH for preventing arterial thrombosis in this experimental model. LMWF also had a lower hemorrhagic risk than LMWH.

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Section: Discussionsupporting

confidence: 69%

Effect of Low Molecular Weight Fucoidan and Low Molecular Weight Heparin in a Rabbit Model of Arterial Thrombosis

Durand¹,

Helley

Zen

et al. 2008

J Vasc Res

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“…The effects of fucoidan on survival rate and spleen function were prophylactic, rather than therapeutic, suggesting that fucoidan requires time to protect target cells against the harmful effects of LPS. Based on previous studies, fucoidan blocks selectin-dependent leukocyte adhesion/rolling [13,14] and inhibit microvascular thrombus formation [15]. It is thus suggested that fucoidan may affect blood circulation dysfunction by LPS in mice.…”

Section: Discussionmentioning

confidence: 93%

Fucoidan Enhances the Survival and Sustains the Number of Splenic Dendritic Cells in Mouse Endotoxemia

Ko¹,

Joo

2011

Korean J Physiol Pharmacol

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Fucoidan is a sulfated polysaccharide derived from brown algae that has been reported to perform multiple biological activities, including immunostimulation. In this study, we investigated whether fucoidan has beneficial effects on endotoxemia induced by LPS, a septic model in mice. The focus of this study was on survival rates and spleen function of the mice upon treatment. W e found that fucoidan had prophylactic effects on the survival rate of mice with endotoxemia. Flow cytometric analysis using antibodies for subset-specific markers revealed that fucoidan profoundly reversed the depleted population of dendritic cells in mice with endotoxemia. According to W estern blot analysis, the spleen cells of LPS/fucoidan-treated mice showed a higher expression of anti-apoptotic molecules compared to those of LPS-treated mice. Also, fucoidan-treated spleen cells were more responsive to mitogens. Taken together, these results demonstrate that fucoidan pre-treatment has beneficial effects on the survival rate and function of the spleen in mice with endotoxemia. This study may broaden the use of fucoidan in clinical fields, especially endotoxemia.

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“…For the study of vascular thrombus formation, we used the opened cremaster muscle preparation, as described originally by Baez [16] and applied as a model of microvascular thrombus formation in previous studies [17][18][19][20]. After the preparation of the cremaster muscle, the animals were allowed to recover from surgery for 15 min before induction of thrombus formation.…”

Section: Mouse Cremaster Muscle Preparationmentioning

confidence: 99%

C-peptide exerts antithrombotic effects that are repressed by insulin in normal and diabetic mice

et al. 2006

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Aims/hypothesis: Diabetic macro-and microangiopathy are associated with a high risk of vascular complications. The diabetic patient exhibits a pathological coagulation state, with an increased synthesis of coagulation factors and plasminogen activator inhibitor 1 (PAI-1) as well as an enhanced aggregation of platelets. Previous studies have shown that C-peptide can reduce leucocyteendothelial cell interaction and improve microvascular blood flow in patients with type 1 diabetes. In the present study, we examined in vivo whether C-peptide is able to reduce platelet activation and through that microvascular thrombus formation. Materials and methods: In the microvessels of cremaster muscle preparations taken from normal and diabetic mice, ferric chloride-induced thrombus formation was analysed using intravital fluorescence microscopy. Results: I.V. administration of C-peptide in high dose (70 nmol/kg), but not in low dose (7 nmol/kg), caused a significant delay in arteriolar and venular thrombus growth in normal and diabetic mice. This effect was repressed by cremaster muscle superfusion with insulin (100 μU/ml) in diabetic animals, but particularly in normal animals. In parallel, immunohistochemistry demonstrated a higher number of PAI-1-expressing vessels in cremaster muscle tissue from control animals and from animals treated with C-peptide and insulin compared with tissue from animals with C-peptide treatment application alone. Conclusions/interpretation: We conclude that C-peptide possesses antithrombotic actions in vivo. A causal role of PAI-1 in this scenario needs to be further addressed. However, the reversal of C-peptide action by insulin may invalidate the use of this peptide as a treatment option to improve rheology and microcirculation in diabetic patients.

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The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P‐ and l‐selectin function in vivo

Cited by 55 publications

References 35 publications

Effect of Low Molecular Weight Fucoidan and Low Molecular Weight Heparin in a Rabbit Model of Arterial Thrombosis

Effect of Low Molecular Weight Fucoidan and Low Molecular Weight Heparin in a Rabbit Model of Arterial Thrombosis

Fucoidan Enhances the Survival and Sustains the Number of Splenic Dendritic Cells in Mouse Endotoxemia

C-peptide exerts antithrombotic effects that are repressed by insulin in normal and diabetic mice

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