Interferon-γ and Intimal Hyperplasia

Abstract

See related article, pages 560–569 Interferon gamma (IFN-γ) is a pleiotropic interferon, and it is known to regulate ≈500 genes.1 It has long been thought to be involved in the pathogenesis of atherosclerosis. The well known properties of IFN-γ include its ability to induce inflammatory genes (eg, ICAM-1, VCAM-1), cell signaling molecules (CD40, CD80, tissue factor, MHC class II antigen) on endothelial cells, and macrophages.2 This results in enhancement of the antigen-presenting properties of macrophages and endothelial cells and induces a proinflammatory phenotype of endothelial cells. IFN-γ also has effects on cholesterol and lipid trafficking. The consensus is that presence of IFN-γ in atherosclerotic plaques has a deleterious effect, possibly by enhancing plaque instability and plaque rupture.2 In this issue of Circulation Research ,3 Wang et al have published a report, the third in a series, which provides compelling evidence that IFN-γ plays a nonredundant role in pathogenesis of alloimmune-induced vascular intimal hyperplasia, a condition that occurs after cardiac allograft transplantation. The results of this study have therapeutic implications for all vascular diseases where smooth muscle hyperplasia occurs, and the mechanisms of its actions are unrelated to the previously described effects of IFN-γ on endothelial cells or macrophages. Cardiac transplantation is a successful therapeutic option for patients with end stage heart failure that cannot be treated by conventional surgery or medication. Whereas 1-year survival has been impacted by improvements in immunosuppression, long-term survival remains relatively unchanged; 10-year survival of combined adult and pediatric transplant recipients is currently 50%.4 A major reason for this is development of cardiac graft vasculopathy (CGV), an occlusive vascular disease of grafted vessels which results in altered blood flow in the arteries and ischemia to the heart. Histologically, there are similarities and differences between CGV and nontransplant atherosclerosis.5 In …