TY - DATA T1 - Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model PY - 2017/12/05 AU - A.I. Fiorelli AU - D.D. Lourenço-Filho AU - E.R. Tavares AU - P.O. Carvalho AU - A.F. Marques AU - P.S. Gutierrez AU - R.C. Maranhão AU - N.A.G. Stolf UR - https://scielo.figshare.com/articles/dataset/Methotrexate_associated_to_lipid_core_nanoparticles_improves_cardiac_allograft_vasculopathy_and_the_inflammatory_profile_in_a_rabbit_heart_graft_model/5670409 DO - 10.6084/m9.figshare.5670409.v1 L4 - https://ndownloader.figshare.com/files/9911536 L4 - https://ndownloader.figshare.com/files/9911539 L4 - https://ndownloader.figshare.com/files/9911542 L4 - https://ndownloader.figshare.com/files/9911545 KW - Nanoemulsions KW - Solid lipid particles KW - Methotrexate KW - Inflammatory mediators KW - LDL receptors N2 - Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg–1·day–1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts. ER -