Identification and Characterization of Two Genes (MIP-1β, VE-CADHERIN) Implicated in Acute Rejection in Human Heart Transplantation Use of Murine Models in Tandem With cDNA Arrays

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-1β (MIP-1β), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistoch...