title: Antiangiogenic treatment prevents adventitial constrictive remodeling in graft arteriosclerosis.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 INSERM, UMR S 872, Les Cordeliers, Paris, France. olivier.thaunatpastu@free.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Thaunat
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Graff-Dubois
authors.forename: Jiangping
authors.initials: J
authors.lastname: Dai
authors.forename: Emilie
authors.initials: E
authors.lastname: Groyer
authors.forename: Houda
authors.initials: H
authors.lastname: Yacoub-Youssef
authors.forename: Chantal
authors.initials: C
authors.lastname: Mandet
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Srini
authors.initials: S
authors.lastname: Kaveri
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caligiuri
authors.forename: Stéphane
authors.initials: S
authors.lastname: Germain
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Antonino
authors.initials: A
authors.lastname: Nicoletti
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000637:transplantation* / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000517:prevention & control*; D003094:Collagen / Q000032:analysis; D005434:Flow Cytometry; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D023421:Models, Animal; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016038:Skin Transplantation / Q000473:pathology / Q000502:physiology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D020533:Angiogenesis Inhibitors; D003094:Collagen