Related Experiment Video
Updated: Sep 17, 2026
A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis
Published on: May 14, 2013
Low molecular weight fucoidan prevents neointimal hyperplasia in rabbit iliac artery in-stent restenosis model
Jean-François Deux1, Anne Meddahi-Pellé, Alain F Le Blanche
1ERIT-M 0204 INSERM, X. Bichat Hospital, University Paris VII, Paris, France.
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 56+/-25 minutes (n=8) after intravenous administration and a constant plasma rate for > or =6 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). Histomorphometric analysis at day 14 indicated that LMW fucoidan reduced intimal hyperplasia by 59% (1.79+/-0.4 versus 0.73+/-0.2 mm2, P<0.0001) and luminal cross-sectional area narrowing by 58% (0.38+/-0.08 versus 0.16+/-0.04, P<0.0001). Blood samples showed no anticoagulant activity due to LMW fucoidan.
Conclusions:
This natural polysaccharide with high affinity for SMCs and sustained plasma concentration markedly reduced intimal hyperplasia, suggesting its use for the prevention of human in-stent restenosis.
Insights
Low molecular weight fucoidan, a natural polysaccharide, significantly reduced smooth muscle cell proliferation and intimal hyperplasia in animal models. This suggests its potential for preventing in-stent restenosis in humans.
Area of Science:
- Biochemistry
- Pharmacology
- Vascular Biology
Background:
- Heparan sulfates regulate smooth muscle cell (SMC) proliferation in the intima.
- Intimal hyperplasia is a key factor in vascular restenosis after interventions.
Purpose of the Study:
- To investigate the effects of low molecular weight (LMW) fucoidan on SMC proliferation in vitro.
- To evaluate the efficacy of LMW fucoidan in preventing intimal hyperplasia in vivo.
Main Methods:
- In vitro studies using rabbit SMCs.
- In vivo studies in rabbit iliac arteries after angioplasty and stent implantation.
- Pharmacokinetic analysis in rats.
Main Results:
- LMW fucoidan reduced rabbit SMC proliferation in vitro and was internalized by SMCs.
- In vivo, LMW fucoidan localized to sites of arterial injury.
- LMW fucoidan significantly reduced intimal hyperplasia by 59% and luminal narrowing by 58% in rabbits.
- No anticoagulant activity was observed.
Conclusions:
- LMW fucoidan, a natural polysaccharide, demonstrates high affinity for SMCs.
- Sustained plasma concentrations of LMW fucoidan were achieved.
- LMW fucoidan effectively reduced intimal hyperplasia, indicating potential for preventing human in-stent restenosis.
