AIP1 in Graft Arteriosclerosis

Graft arteriosclerosis (GA), the major cause of late cardiac allograft failure, is characterized by a diffuse, concentric arterial intimal hyperplasia composed of infiltrating host T cells, macrophages, and predominantly graft-derived smooth muscle–like cells that proliferate and elaborate extracellular matrix, resulting in luminal obstruction and allograft ischemia. Interferon-γ (IFN-γ), a proinflammatory cytokine produced by effector T cells, is a critical mediator for smooth muscle–like cell proliferation. We have exploited the power of mouse genetics to examine the function of AIP1, a signaling adaptor molecule involved in vascular inflammation, in two newly established IFN-γ–mediated models of GA. Our data suggest that AIP1 inhibits intimal formation in GA by downregulating IFN-γ–activated migratory and proliferative signaling pathways in smooth muscle–like cells.