Heparin‐like polymers modulate proinflammatory cytokine production by lipopolysaccharide‐stimulated human monocytes

Anastase-Ravion, Sylvie; Carreno, Marie‐Paule; Blondin, Catherine; Ravion, Olivier; Champion, J.; Chaubet, Frédéric; Haeffner‐Cavaillon, Nicole; Letourneur, Didier

doi:10.1002/jbm.10112.abs

Cited by 7 publications

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“…Reduced adventitial cell infiltration and medial preservation in the allograft may be explained by the general anti-inflammatory effects of LMWF. For instance, LMWF has been found to interfere with the inflammatory response, in particular the release of cytokines by activated monocytes (29,30). Indeed, direct inhibition by LMWF of selectin-mediated leukocyte recruitment and neutrophil infiltration may be implicated in the protective effects of LMWF on the arterial wall (31).…”

Section: Discussionmentioning

confidence: 98%

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia After Aortic Allografting

Fréguin-Bouilland

Alkhatib²,

David³

et al. 2007

Transplantation

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Section: Discussionmentioning

confidence: 98%

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia After Aortic Allografting

Fréguin-Bouilland

Alkhatib²,

David³

et al. 2007

Transplantation

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“…14 HMW fucoidan reduces in vivo neutrophil adhesion and leukocyte migration. 33,34 Our recent data indicate that sulfated polysaccharides, including fucoidan, inhibit the release of proinflammatory cytokines/chemokines by activated monocytes, 35 which may be relevant for the inhibition of intimal hyperplasia. 36 (3) We and other groups have described that HMW and LMW fucoidans have antithrombotic activities and reduce platelet aggregation, an important stimulus of restenosis.…”

Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Deux

Meddahi‐Pellé

Blanche

et al. 2002

ATVB

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Objective-Smooth muscle cell (SMC) proliferation within the intima is regulated by heparan sulfates. We studied a low molecular weight (LMW) fucoidan (sulfated polysaccharide from brown seaweed) on SMC proliferation in vitro and intimal hyperplasia in vivo. Methods and Results-In vitro study revealed that LMW fucoidan reduces rabbit SMC proliferation and is internalized in SMC perinuclear vesicles. On rabbit iliac arteries perfused in vivo with fluorolabeled LMW fucoidan after angioplasty, the labeling was mainly located on sites of injury. Pharmacokinetic studies showed that LMW fucoidan exhibited in rats an elimination half-life of 56Ϯ25 minutes (nϭ8) after intravenous administration and a constant plasma rate for Ն6 hours after intramuscular administration. After stent implantation in their iliac arteries, rabbits were also treated with LMW fucoidan (5 mg/kg IM twice a day Key Words: fucoidan Ⅲ hyperplasia Ⅲ restenosis Ⅲ stent Ⅲ vascular smooth muscle cell proliferation I ntimal hyperplasia due to migration and proliferation of smooth muscle cells (SMCs) from the media to the intima is a major component of restenosis after stent implantation. 1,2 Polysaccharides constitute a large family of molecules capable of developing molecular interactions with cellular targets within the arterial wall. 3 For instance, heparin, a natural sulfated polysaccharide, displays pleiotropic effects independent of the anticoagulant activity, including SMC growth inhibition, 4 anti-inflammatory activity, 5 and growth factor protection. 6 Fucoidan is a sulfated polysaccharide extracted from brown seaweed that reduces rat SMC proliferation in vitro in a more intensive manner than heparin. 7 We recently succeeded in producing and characterizing new homogeneous fractions of low molecular weight (LMW) fucoidan with low anticoagulant activity.The aims of the present study were to investigate the ability of LMW fucoidan to regulate vascular SMCs. For this purpose, we first tested the ability of LMW fucoidan to inhibit rabbit SMC proliferation in vitro. We explored the pharmacokinetics of LMW fucoidan injected in rats and the effect of LMW fucoidan on intimal hyperplasia. The results described below indicate that LMW fucoidan is a strong inhibitor of intimal hyperplasia and may be potentially relevant for the treatment of in-stent restenosis. Methods PolysaccharidesLMW fucoidan was isolated and hydrolyzed by a radical depolymerization process 8 from high molecular weight (HMW) extracts of brown marine algae. The characteristics of LMW fucoidan according to previously reported analytical methods 9 are as follows: weightaverage molecular mass 8Ϯ1 kDa; fucose content 35% (wt/wt); uronic acid content 3% (wt/wt); and sulfate content 34% (wt/wt). The anticoagulant activity in vitro of the LMW fucoidan was measured by an activated partial thromboplastin time (APTT), and the amount of LMW fucoidan required to obtain an APTT of 80 seconds (control 40 seconds) was 25 g/mL. 10 The anticoagulant activity in vivo of LMW fucoidan was measured in rabbit...

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“…In addition, O‐desulfated heparin prevented dysfunction of endothelial‐dependent coronary relaxation following ischemic injury and inhibited translocation of the proinflammatory transcription nuclear factor‐κB (NF‐κB) from the cytoplasm to the nucleus in human endothelial cells and decreased NF‐κB DNA binding in human endothelium and ischemic‐reperfused rat myocardium [16]. Recently, fucan and dextran derivatives and heparin were found to modulate, in a dose‐dependent manner, the release of proinflammatory cytokines by resting or LPS‐stimulated human monocytes and to interact with monocyte surfaces by inhibiting LPS‐binding to monocyte membranes [17].…”

Section: Introductionmentioning

confidence: 99%

Cytokine gene expression and production by human LPS‐stimulated mononuclear cells are inhibited by sulfated heparin‐like semi‐synthetic derivatives

Gori

Attanasio

Gazzini

et al. 2004

Journal of Thrombosis and Haemostasis

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Summary. Background: The K5 polysaccharide obtained from Escherichia coli strain 010:K5:H4 is a polymer of the disaccharidic unit formed by D-glucuronic acid and Nacetylglucosamine. This structure is akin to N-acetylheparosan, the precursory polymer of heparin and of heparan sulfate. This structural affinity with N-acetylated heparin and with desulfated heparin makes the K5 polysaccharide extremely useful for the preparation of sulfated heparin-like semi-synthetic derivatives. It has been demonstrated that heparins are able to inhibit tissue factor and cytokine production and expression by human monocytes. Objective: The aim of this study was to evaluate the effects of four different heparin-like semi-synthetic derivatives on inflammatory cytokine production and expression by human mononuclear cells. Results: The simultaneous addition of lipopolysaccharide (LPS; 0.2 and 10 lg mL ), K5-OS or K5-N, OS epi at 5 and 10 lg mL )1 markedly decreased TNF-a mRNA expression. Conclusions: These results indicate that the sulfated heparin-like semi-synthetic derivatives K5-OS and K5-N, OS epi are able to inhibit both expression and production of inflammatory cytokines, whereas they do not influence the anti-inflammatory cytokine IL-10, suggesting a potential role for these products as modulators of inflammatory reactions.

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Heparin‐like polymers modulate proinflammatory cytokine production by lipopolysaccharide‐stimulated human monocytes

Cited by 7 publications

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Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia After Aortic Allografting

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia After Aortic Allografting

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Cytokine gene expression and production by human LPS‐stimulated mononuclear cells are inhibited by sulfated heparin‐like semi‐synthetic derivatives

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