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.
Interdepartmental Program in Vascular Biology and Therapeutics and the Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA. wang.min@yale.edu
Wang
W
Min
Jordan S
JS
Pober
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D003324:Coronary Artery Disease / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058426:Neointima; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
C462952:DAB2IP protein, human; C561450:Dab2ip protein, mouse; D020703:ras GTPase-Activating Proteins; D007371:Interferon-gamma