title: T-cadherin expression in cardiac allograft vasculopathy: bench to bedside translational investigation.
abstract: BACKGROUND
  Coronary allograft vasculopathy (CAV) is the major limiting factor for long term survival after heart transplantation. The aim of this study was to identify gene candidates implicated in human CAV using a rat aortic allograft model in tandem with microarrays and quantitative real time PCR (Q-PCR).
  
  
  METHODS
  Rat abdominal aortas were isografted (5) or allografted (5) from Brown-Norway to Lewis rats and grafts were harvested after day 8, 25 and 60. Agilent microarrays were then used to highlight differentially expressed genes between isografted and allografted rat aortas. Further investigation of a selected candidate gene was performed on human coronary arteries.
  
  
  RESULTS
  1829, 2582 and 1925 genes (fold changes >2 or <2 and p values <0.05) were differentially expressed at day 8, 25 and 60 respectively between isografs and allografts. Seventeen candidate genes were selected according to significant differential expression at day 60. These rat candidate genes were then validated by quantitative real time polymerase chain reaction (Q-PCR). One of these candidate genes, T-Cadherin (T-Cad) was further investigated, using immunohistochemistry (IHC), in human coronary arteries showing CAV compared to classical atherosclerosis present in ischemic cardiomyopathy (ICM) and normal coronary arteries present in dilated cardiomyopathy (DCM). Results showed an over expression of T-Cad in CAV and classical atherosclerosis compared to normal coronary arteries.
  
  
  CONCLUSIONS
  T-Cad was found to be over expressed in CAV. T-Cad could potentially act as a trigger for smooth muscle cells (SMCs) proliferation and vascular remodelling observed in CAV leading to a diffuse narrowing of the arterial lumen.
authors.affiliation: King's College London, London, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Collot-Teixeira
authors.forename: John L
authors.initials: JL
authors.lastname: McGregor
authors.forename: Kira
authors.initials: K
authors.lastname: Morser
authors.forename: Lara
authors.initials: L
authors.lastname: Chalabreysse
authors.forename: Chris
authors.initials: C
authors.lastname: McDermott-Roe
authors.forename: Catherine
authors.initials: C
authors.lastname: Cerutti
authors.forename: Adriana
authors.initials: A
authors.lastname: Guzman
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Pascale
authors.initials: P
authors.lastname: Boissonnat
authors.forename: Laurent
authors.initials: L
authors.lastname: Sebbag
authors.forename: Françoise
authors.initials: F
authors.lastname: Thivolet-Bejui
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Bricca
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Obadia
authors.forename: Ana
authors.initials: A
authors.lastname: Roussoulières
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000637:transplantation; D015820:Cadherins / Q000378:metabolism*; D049109:Cell Proliferation; D003331:Coronary Vessels / Q000378:metabolism / Q000637:transplantation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D015820:Cadherins; C099972:H-cadherin