Wong ChunYu, Bezhaeva Taisiya, Rothuizen Tonia C, Metselaar Josbert M, de Vries Margreet R, Verbeek Floris P R, Vahrmeijer Alexander L, Wezel Anouk, van Zonneveld Anton-Jan, Rabelink Ton J, Quax Paul H A, Rotmans Joris I
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Center, Leiden, The Netherlands.
Sci Rep. 2016 Jul 27;6:30439. doi: 10.1038/srep30439.
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.
用于血液透析通路的动静脉内瘘(AVF)的1年原发性通畅率仅为60%,主要是由于向外重塑不足和内膜增生导致的成熟失败。确切的病理生理学尚不清楚,但炎症性血管反应被认为起重要作用。在本研究中,我们证明靶向脂质体递送泼尼松龙可增加小鼠模型中AVF的向外重塑。脂质体聚集在静脉流出道的吻合后区域,在失败的AVF中该区域血管病变最为突出。在组织学水平上,我们观察到血管壁中淋巴细胞和粒细胞减少。此外,体外实验证明脂质体泼尼松龙对巨噬细胞具有强大的抗炎作用。因此,脂质体泼尼松龙治疗可能是改善AVF成熟的一种有价值的策略。