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Article Dans Une Revue Transplantation Année : 2008

Antiangiogenic treatment prevents adventitial constrictive remodeling in graft arteriosclerosis

Olivier Thaunat
Liliane Louedec
  • Fonction : Auteur
Stéphanie Graff-Dubois
Jiangping Dai
  • Fonction : Auteur
Emilie Groyer
  • Fonction : Auteur
Houda Yacoub-Youssef
Chantal Mandet
  • Fonction : Auteur
Patrick Bruneval
Srini Kaveri
  • Fonction : Auteur
Giuseppina Caligiuri
  • Fonction : Auteur
Jean-Baptiste Michel
  • Fonction : Auteur
Antonino Nicoletti

Résumé

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\textless0.0001) in the rat aortic interposition model of graft arteriosclerosis. The associated decreased entry of inflammatory cells (44%; P\textless0.00001) resulted in drastic reduction of collagen deposition (57%; P\textless0.0001) 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\textless0.0001). 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.
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Dates et versions

hal-02142761 , version 1 (28-05-2019)

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Olivier Thaunat, Liliane Louedec, Stéphanie Graff-Dubois, Jiangping Dai, Emilie Groyer, et al.. Antiangiogenic treatment prevents adventitial constrictive remodeling in graft arteriosclerosis. Transplantation, 2008, 85 (2), pp.281--289. ⟨10.1097/TP.0b013e318160500a⟩. ⟨hal-02142761⟩
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