on May 16, 2005
Published online before print May 16, 2005, doi: 10.1161/CIRCULATIONAHA.104.482612
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Submitted on June 8, 2003
From INSERM U331/EA 1582 Faculté de Médecine RTH Laennec, Lyon, France (A.L.S.R., C.C., J.L.M.); Departments of Cardiac Transplantation (A.L.S.R., P.B., L.S., O.B.), Cardiac Surgery (O.R., G.D., J.-F.O., J.N.), and Pathology (L.C., F.T.-B), Hôpital Cardiologique Louis Pradel, Lyon, France; Department of Hematology, Hôpital Lyon Sud, Lyon, France (C.T.); EMIU 0226, Lyon, France (L.S.); and Cardiovascular Division, King’s College, and Thrombosis Research Institute, Genomics and Atherothrombosis, London, UK (J.L.M.). * To whom correspondence should be addressed. E-mail: ana.roussoulieres{at}chu-lyon.fr.
Background--Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection. Methods and Results--Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1 Conclusions--We have demonstrated that the upregulation of MIP-1
Revised on January 8, 2005
Accepted on January 19, 2005
Identification and Characterization of Two Genes (MIP-1
A. L.S. Roussoulières MD, PhD*, 
, VE-CADHERIN) Implicated in Acute Rejection in Human Heart Transplantation. Use of Murine Models in Tandem With cDNA Arrays
(MIP-1), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model. and downregulation of VE-cadherin may strongly participate in human acute heart rejection.
Key words: genes • immunohistochemistry • polymerase chain reactions • rejection • transplantation