Identification and Characterization of Two Genes (MIP-1β, VE-CADHERIN) Implicated in Acute Rejection in Human Heart Transplantation

作者：Ana L.S. Roussoulieres, Olivier Raisky, Lara Chalabreysse, Georges Dureau, Catherine Cerutti, Catherine Thiéblemont, P. Boissonnat, Laurent Sebbag, Jean François Obadia, J Ninet, Olivier H. Bastien, F. Thivolet-Béjui, John Louis McGregor · 发表于：Circulation · 年份：2005 · DOI：10.1161/circulationaha.104.482612 · 被引用次数：9 · 研究领域：Cardiac Fibrosis and Remodeling、Transplantation: Methods and Outcomes、Immune Response and Inflammation

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-1beta (MIP-1beta), 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. CONCLUSIONS: We have demonstrate...