title: Liposomal prednisolone inhibits vascular inflammation and enhances venous outward remodeling in a murine arteriovenous fistula model.
abstract: Arteriovenous fistulas (AVF) for hemodialysis access have a 1-year primary patency rate of only 60%, mainly as a result of maturation failure that is caused by insufficient outward remodeling and intimal hyperplasia. The exact pathophysiology remains unknown, but the inflammatory vascular response is thought to play an important role. In the present study we demonstrate that targeted liposomal delivery of prednisolone increases outward remodeling of the AVF in a murine model. Liposomes accumulate in the post-anastomotic area of the venous outflow tract in which the vascular pathology is most prominent in failed AVFs. On a histological level, we observed a reduction of lymphocytes and granulocytes in the vascular wall. In addition, a strong anti-inflammatory effect of liposomal prednisolone on macrophages was demonstrated in vitro. Therefore, treatment with liposomal prednisolone might be a valuable strategy to improve AVF maturation.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Center, Leiden, The Netherlands.
authors.forename: ChunYu
authors.initials: C
authors.lastname: Wong
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Center, Leiden, The Netherlands.
authors.forename: Taisiya
authors.initials: T
authors.lastname: Bezhaeva
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Center, Leiden, The Netherlands.
authors.forename: Tonia C
authors.initials: TC
authors.lastname: Rothuizen
authors.affiliation: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands.|Enceladus Pharmaceuticals BV, The Netherlands.
authors.forename: Josbert M
authors.initials: JM
authors.lastname: Metselaar
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Center, Leiden, The Netherlands.|Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Margreet R
authors.initials: MR
authors.lastname: de Vries
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Floris P R
authors.initials: FP
authors.lastname: Verbeek
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Vahrmeijer
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.|Leiden Academic Center for Drug Research, Leiden, The Netherlands.
authors.forename: Anouk
authors.initials: A
authors.lastname: Wezel
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Center, Leiden, The Netherlands.
authors.forename: Anton-Jan
authors.initials: AJ
authors.lastname: van Zonneveld
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Center, Leiden, The Netherlands.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Center, Leiden, The Netherlands.|Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Paul H A
authors.initials: PH
authors.lastname: Quax
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Center, Leiden, The Netherlands.
authors.forename: Joris I
authors.initials: JI
authors.lastname: Rotmans
mesh_terms: D000818:Animals; D001164:Arteriovenous Fistula / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017252:CD3 Complex / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D007601:Jugular Veins / Q000187:drug effects / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D014654:Vascular Patency / Q000187:drug effects; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D008081:Liposomes; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D011239:Prednisolone; D017493:Leukocyte Common Antigens; D020782:Matrix Metalloproteinases