CKD accelerates development of neointimal hyperplasia in arteriovenous fistulas.
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.
Kokubo
Taku
T
Department of Cardiovascular Surgery, Asahikawa Medical University, Hokkaido, Japan.
Ishikawa
Noriyuki
N
Uchida
Hisashi
H
Chasnoff
Sara E
SE
Xie
Xun
X
Mathew
Suresh
S
Hruska
Keith A
KA
Choi
Eric T
ET
D000818:Animals; D001164:Arteriovenous Fistula / Q000473:pathology*; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D001853:Bone Marrow / Q000503:physiopathology; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D017536:Carotid Artery, Common / Q000473:pathology; D054443:Cell Migration Assays; D049109:Cell Proliferation; D006965:Hyperplasia; D007601:Jugular Veins / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D053495:Osteopontin / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000473:pathology* / Q000503:physiopathology
D055419:Bone Morphogenetic Protein 7; D053495:Osteopontin