Document Detail

Antiangiogenic treatment prevents adventitial constrictive remodeling in graft arteriosclerosis.
MedLine Citation:
PMID:  18212634     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Lumen loss in graft arteriosclerosis is the consequence of the development of a thick neointima and constrictive arterial remodeling. The latter is due to adventitial chronic inflammation and excessive perivascular collagen deposition. We reasoned that blockade of the portal of entry of inflammatory effectors may constitute a strategy to prevent constrictive arterial remodeling. METHODS AND RESULTS: We found that an anti-angiogenic therapy (ABT-510 nonapeptide), devoid of direct immunomodulatory properties, dramatically reduced adventitial angiogenesis by 66% (P<0.0001) in the rat aortic interposition model of graft arteriosclerosis. The associated decreased entry of inflammatory cells (44%; P<0.00001) resulted in drastic reduction of collagen deposition (57%; P<0.0001) thereby preventing subsequent adventitial constrictive remodeling and reduction of lumen surface area (5.26+/-0.74 vs. 8.58+/-2.48 microm2; Control vs. ABT-510-treated rats; P<0.0001). ABT-510 had no effect on the development of the neointima. CONCLUSION: This work supports the idea that targeting angiogenesis may act synergistically with conventional immunosuppressive therapy in preventing graft arteriosclerosis, a crucial feature of chronic graft rejection.
Olivier Thaunat; Liliane Louedec; Stéphanie Graff-Dubois; Jiangping Dai; Emilie Groyer; Houda Yacoub-Youssef; Chantal Mandet; Patrick Bruneval; Srini Kaveri; Giuseppina Caligiuri; Stéphane Germain; Jean-Baptiste Michel; Antonino Nicoletti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  85     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-23     Completed Date:  2008-04-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  281-9     Citation Subset:  IM    
1 INSERM, UMR S 872, Les Cordeliers, Paris, France.
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MeSH Terms
Angiogenesis Inhibitors / therapeutic use*
Aorta / drug effects,  pathology,  transplantation*,  ultrastructure
Arteriosclerosis / prevention & control*
Collagen / analysis
Flow Cytometry
Lymphocyte Culture Test, Mixed
Models, Animal
Rats, Inbred BN
Rats, Inbred Lew
Skin Transplantation / pathology,  physiology
Transplantation, Homologous
Transplantation, Isogeneic
Reg. No./Substance:
0/Angiogenesis Inhibitors; 9007-34-5/Collagen

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