title: Learning from rejection: what transplantation teaches us about (other) vascular pathologies.
abstract: Allograft vasculopathy is an accelerated intimal hyperplastic lesion leading to progressive vascular stenosis; it represents the major long-term limitation to successful solid organ transplant. Although allograft vasculopathy is not formally an autoimmune disease, nor does it constitute a major cause of cardiovascular disease on a purely numerical basis, its pathogenesis provides an important window on the mechanisms by which immune injury can drive more common vascular pathologic entities. Thus, insights gleaned from vascularized solid organ transplants can shed new mechanistic (and therapeutic) light on: 1) the intimal vascular responses accompanying typical atherosclerosis and other inflammatory vessel diseases (e.g., scleroderma); 2) the pathogenesis of vascular stenosis versus aneurysm formation; 3) the sources of intimal smooth muscle cells in the healing of any vascular injury; and 4) the mechanisms by which smooth muscle cells are recruited into intimal lesions. Indeed, research on allograft vasculopathy has led to the understanding that interferon-γ plays a similar pathogenic role in a host of vascular stenosing lesions-and that Th2 cytokines can drive vascular remodeling and aneurysm formation. Moreover, circulating precursors (and not just medial smooth muscle cells) contribute to the intimal hyperplasia seen in atherosclerosis and in-stent restenosis. That non-vessel smooth muscle cells can be recruited to sites of vessel injury further suggests that chemokine and adhesion molecule interactions may be viable targets to limit vascular stenosis in a wide range of vascular lesions. This review will describe the pathogenesis of allograft vasculopathy, and will relate how understanding the underlying pathways informs our understanding of both human transplant-associated disease, as well as other human vascular pathologies.
authors.affiliation: Pathology and Health Sciences and Technology, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur/NRB 730D, Boston, MA 02115, USA. Electronic address: rmitchell@rics.bwh.harvard.edu.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D003251:Constriction, Pathologic / Q000209:etiology / Q000517:prevention & control*; D006084:Graft Rejection / Q000150:complications / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000276:immunology*; D016377:Organ Transplantation; D018418:Th2 Cells / Q000276:immunology; D014652:Vascular Diseases / Q000150:complications / Q000276:immunology*; D014945:Wound Healing
chemical_list: D007371:Interferon-gamma
keywords: Allograft vasculopathy; Aneurysm; Atherosclerosis; Chemokine; Intimal hyperplasia