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: ChunYu Wong, Taisiya Bezhaeva, Tonia C Rothuizen, Josbert M Metselaar, Margreet R de Vries, Floris P R Verbeek, Alexander L Vahrmeijer, Anouk Wezel, Anton-Jan van Zonneveld, Ton J Rabelink, Paul H A Quax, Joris I Rotmans
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 30439 (07 27 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27460883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD3 Complex
• Cytokines
• Liposomes
• RNA, Messenger
• Tissue Inhibitor of Metalloproteinases
• Prednisolone
• Leukocyte Common Antigens
• Matrix Metalloproteinases

Topics

• Animals
• Arteriovenous Fistula (drug therapy, pathology, surgery)
• CD3 Complex (metabolism)
• Cells, Cultured
• Cytokines (metabolism)
• Disease Models, Animal
• Inflammation (drug therapy, pathology)
• Jugular Veins (drug effects, pathology)
• Leukocyte Common Antigens (metabolism)
• Liposomes
• Macrophages (drug effects, metabolism, pathology)
• Male
• Matrix Metalloproteinases (genetics, metabolism)
• Mice, Inbred C57BL
• Prednisolone (pharmacology, therapeutic use)
• RNA, Messenger (genetics, metabolism)
• Tissue Inhibitor of Metalloproteinases (genetics, metabolism)
• Vascular Patency (drug effects)
• Vascular Remodeling (drug effects)