title: Direct and indirect effects of alloantibodies link neointimal and medial remodeling in graft arteriosclerosis.
abstract: OBJECTIVE
  Chronic vascular rejection, the main cause of allograft failure, is characterized by the destruction of smooth muscle cells (SMCs) in the media concomitantly with the proliferation of SMCs in the adjacent neointima. We hypothesized that alloantibodies might be responsible for these 2 opposite but coordinated events.
  
  
  RESULTS
  We used the rat aortic interposition model of chronic vascular rejection. During the rejection process, a neointima composed of proliferating SMCs from the recipient developed, whereas the SMCs in the media, all of donor origin, underwent apoptosis. Alloantibody deposition was detected only in the media. Using in vitro cultures experiments, we observed that alloantibody binding to donor SMCs exerts (1) a rapid upregulation of the transcription of growth factors genes, followed by (2) the induction of apoptosis after 24 hours. The transient production of growth factors by donor SMCs in response to the binding of alloantibodies induced the proliferation of recipient SMCs in culture supernatant transfer experiments. Additional data suggest that among the repertoire of alloantibodies, those directed against major histocompatibility complex I might carry the remodeling effect.
  
  
  CONCLUSIONS
  Our data suggest that during chronic vascular rejection, alloantibody binding to donor medial SMCs is a crucial event that links neointimal and medial remodeling.
authors.affiliation: Université Pierre et Marie Curie-Paris6, INSERM UMRS 681, Centre de recherche des 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: Jianping
authors.initials: J
authors.lastname: Dai
authors.forename: Florence
authors.initials: F
authors.lastname: Bellier
authors.forename: Emilie
authors.initials: E
authors.lastname: Groyer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delignat
authors.forename: Anh-Thu
authors.initials: AT
authors.lastname: Gaston
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caligiuri
authors.forename: Etienne
authors.initials: E
authors.lastname: Joly
authors.forename: Didier
authors.initials: D
authors.lastname: Plissonnier
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Antonino
authors.initials: A
authors.lastname: Nicoletti
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000503:physiopathology; D001161:Arteriosclerosis / Q000276:immunology / Q000503:physiopathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D002908:Chronic Disease; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006083:Graft Occlusion, Vascular / Q000276:immunology / Q000503:physiopathology*; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D006133:Growth Substances / Q000235:genetics; D007518:Isoantibodies / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D007700:Kinetics; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014019:Tissue Donors; D014158:Transcription, Genetic; D018183:Transplantation Chimera; D017539:Tunica Intima / Q000276:immunology / Q000503:physiopathology*; D017540:Tunica Media / Q000276:immunology / Q000503:physiopathology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D006133:Growth Substances; D007518:Isoantibodies