T-cadherin expression in cardiac allograft vasculopathy: bench to bedside translational investigation.
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.
Collot-Teixeira
Sophie
S
King's College London, London, UK.
McGregor
John L
JL
Morser
Kira
K
Chalabreysse
Lara
L
McDermott-Roe
Chris
C
Cerutti
Catherine
C
Guzman
Adriana
A
Michel
Jean-Baptiste
JB
Boissonnat
Pascale
P
Sebbag
Laurent
L
Thivolet-Bejui
Françoise
F
Bricca
Gianpiero
G
Obadia
Jean-François
JF
Roussoulières
Ana
A
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
D015820:Cadherins; C099972:H-cadherin