title: Low molecular weight fucoidan prevents neointimal hyperplasia after aortic allografting.
abstract: BACKGROUND
  Fucoidan, a new low molecular weight sulfated polysaccharide (LMWF), has previously been shown to mobilize bone marrow-derived progenitors cells via stimulation of stromal derived factor (SDF)-1 release. Mobilized progenitor cells have been suggested to repair intimal lesions after immune-mediated endothelial injury and thus prevent intimal proliferation. The aim of this study was to evaluate the effect of LMWF treatment in a rat aortic allograft model of transplant arteriosclerosis (TA).
  
  
  METHODS
  Aortic grafts were performed in Brown Norway (BN, donor) and Lewis (Lew, recipient) rats. The recipient rats were treated with LMWF (5 mg/kg/day) and sacrificed at 30 days. To determine the role of SDF-1 in mediating the effects of LMWF, a specific inhibitor of the SDF-1 receptor CXCR4, AMD 3100 (20 microg/kg/day), was used. The grafted segments were evaluated by morphometric (histochemical) analyses.
  
  
  RESULTS
  Untreated aortic allografts exhibited severe intimal proliferation, indicative of TA. In contrast, LMWF treatment significantly prevented allograft intimal proliferation as compared with controls (5.7+/-3 vs. 66.2+/-6 microm, P<0.01) and permitted a normalization of the intima/media ratio (0.1+/-0.1 vs. 1.7+/-0.3, P<0.01). Further, LMWF treatment stimulated allograft reendothelialization, as evidenced by strong intimal endothelial nitric oxide synthase antibody and CD31 signals. Unexpectedly, AMD treatment failed to prevent the protective effect of LMWF on intimal thickening and AMD treatment alone was found to reduced intimal proliferation in allografts.
  
  
  CONCLUSIONS
  We found that LMWF treatment reduced intimal thickness and induced the presence of an endothelial cell lining in the vascular graft at 30 days. Our findings may suggest a novel therapeutic strategy in the prevention of TA.
authors.affiliation: Inserm U644, IFRMP 23, Rouen University Hospital-Charles Nicolle, Rouen, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Fréguin-Bouilland
authors.forename: Bassam
authors.initials: B
authors.lastname: Alkhatib
authors.forename: Nathalie
authors.initials: N
authors.lastname: David
authors.forename: Françoise
authors.initials: F
authors.lastname: Lallemand
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Henry
authors.forename: Michel
authors.initials: M
authors.lastname: Godin
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Didier
authors.initials: D
authors.lastname: Plissonnier
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000517:prevention & control; D001596:Benzylamines; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood; D000080027:Cyclams; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D008970:Molecular Weight; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology*; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D014180:Transplantation / Q000009:adverse effects; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D011134:Polysaccharides; D019718:Receptors, CXCR4; C007789:fucoidan; C088327:plerixafor