CKD Accelerates Development of Neointimal Hyperplasia in Arteriovenous Fistulas
- 1 June 2009
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 20 (6), 1236-1245
- https://doi.org/10.1681/asn.2007121312
Abstract
Arteriovenous (AV) access failure resulting from venous neointimal hyperplasia is a major cause of morbidity in patients with ESRD. To understand the role of chronic kidney disease (CKD) in the development of neointimal hyperplasia, we created AV fistulae (common carotid artery to jugular vein in an end-to-side anastomosis) in mice with or without CKD (renal ablation or sham operation). At 2 and 3 wk after operation, neointimal hyperplasia at the site of the AV anastomosis increased 2-fold in animals with CKD compared with controls, but cellular proliferation in the neointimal hyperplastic lesions did not significantly differ between the groups, suggesting that the enhanced neointimal hyperplasia in the setting of CKD may be secondary to a migratory phenotype of vascular smooth muscle cells (VSMC). In ex vivo migration assays, aortic VSMC harvested from mice with CKD migrated significantly greater than VSMC harvested from control mice. Moreover, animals with CKD had higher serum levels of osteopontin, which stimulates VSMC migration. When we treated animals with bone morphogenic protein-7, which promotes VSMC differentiation, before creation of the AV anastomosis, the effect of CKD on the development of neointimal hyperplasia was eliminated. In summary, CKD accelerates development of neointimal hyperplasia at the anastomotic site of an AV fistula, and administration of bone morphogenic protein-7 neutralizes this effect.Keywords
This publication has 41 references indexed in Scilit:
- The Mechanism of Phosphorus as a Cardiovascular Risk Factor in CKDJournal of the American Society of Nephrology, 2008
- Characterization of neointima lesions associated with arteriovenous fistulas in a mouse modelKidney International, 2006
- Arsenite Regulates Cystic Fibrosis Transmembrane Conductance Regulator and P-glycoprotein: Evidence of Pathway IndependenceCellular Physiology and Biochemistry, 2005
- Antithrombotic activity of dermatan sulfate in heparin cofactor II-deficient miceBlood, 2004
- A Model of Primary Atherosclerosis and Post-Angioplasty Restenosis in MiceThe American Journal of Pathology, 2003
- Long-term outcome of dialysis patients in the United States with coronary revascularization proceduresKidney International, 1999
- Leukocyte-polytetrafluoroethylene interaction enhances proliferation of vascular smooth muscle cells via tumor necrosis factor-α secretionKidney International, 1997
- Early experience with stretch polytetrafluoroethylene grafts for haemodialysis access surgery: Results of a prospective randomised studyEuropean Journal of Vascular and Endovascular Surgery, 1995
- The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro.JCI Insight, 1995
- Osteopontin-Stimulated Vascular Smooth Muscle Cell Migration Is Mediated by β3 IntegrinExperimental Cell Research, 1994