title: TGF-beta, IL-6, IL-17 and CTGF direct multiple pathologies of chronic cardiac allograft rejection.
abstract: Cardiac transplantation is an effective treatment for heart failure refractive to therapy. Although immunosuppressive therapeutics have increased first year survival rates, chronic rejection remains a significant barrier to long-term graft survival. Chronic rejection manifests as patchy interstitial fibrosis, vascular occlusion and progressive loss of graft function. Recent evidence from experimental and patient studies suggests that the development of cardiomyocyte hypertrophy is another hallmark of chronic cardiac allograft rejection. This pathologic hypertrophy is tightly linked to the immune cytokine IL-6, which promotes facets of chronic rejection in concert with TGF-beta and IL-17. These factors potentiate downstream mediators, such as CTGF, which promote the fibrosis associated with the disease. In this article, we summarize contemporary findings that have revealed several elements involved in the induction and progression of chronic rejection of cardiac allografts. Further efforts to elucidate the interplay between these factors may direct the development of targeted therapies for this disease.
authors.affiliation: Division of Pulmonary & Critical Care, Department of Internal Medicine, University of Michigan Medical Center, 6240 MSRBIII/0624, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA. boothaj@med.umich.edu
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Booth
authors.forename: D Keith
authors.initials: DK
authors.lastname: Bishop
mesh_terms: D055513:Connective Tissue Growth Factor / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D016027:Heart Transplantation; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor