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Chronic kidney disease accelerates endothelial barrier dysfunction in a mouse model of an arteriovenous fistula.
Liang, Anlin; Wang, Yun; Han, Guofeng; Truong, Luan; Cheng, Jizhong.
Afiliação
  • Liang A; Division of Nephrology, Baylor College of Medicine, Houston, TX 77030, USA.
Am J Physiol Renal Physiol ; 304(12): F1413-20, 2013 Jun 15.
Article em En | MEDLINE | ID: mdl-23576636
ABSTRACT
Hemodialysis patients depend on arteriovenous fistulas (AVF) for vascular access. Unfortunately, their 2-yr primary patency rate is only 60% because of AVF clog due to intimal hyperplasia at the venous anastomosis. Chronic kidney disease (CKD) can increase neointima formation by unknown mechanisms. A new AVF mouse model was created, and the mechanisms of CKD on neointima formation in AVFs were investigated. We created AVFs in mice by anastomosing the common carotid artery to the internal jugular vein. CKD was induced [BUN (blood urea nitrogen) in control and CKD mice, 33.3 ± 3.9 vs. 114.2 ± 12.1 mg/dl, P < 0.05]. After 1 day, there was endothelial cell loss and CD41-positive platelet aggregation, especially in the venous anastomosis. An invasion of macrophages and neutrophils peaked at 1 wk after surgery. Neointima formation (smooth muscle cell accumulation and extracellular matrix deposition) increased progressively over 4 wk. Mice with CKD had ~45% (P < 0.05) more neointima formation than control mice. CKD decreased vascular endothelial-cadherin expression in endothelial cells and delayed regeneration of the endothelium. CKD also increased inflammatory cells (Mac-2-positive or CD45-positive) in AVFs at 2 wk. Finally, AVFs were "leakier" (increased accumulation of Evans blue) in CKD mice at 7 and 14 days than control mice. We find that CKD increases neointima formation and endothelial barrier dysfunction. We have created a mouse model of AVF with characteristics similar to failed AVFs in patients. The model will allow testing of strategies directed at improving AVF function in CKD patients.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Derivação Arteriovenosa Cirúrgica / Endotélio / Insuficiência Renal Crônica / Neointima Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Physiol Renal Physiol Assunto da revista: FISIOLOGIA / NEFROLOGIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Derivação Arteriovenosa Cirúrgica / Endotélio / Insuficiência Renal Crônica / Neointima Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Physiol Renal Physiol Assunto da revista: FISIOLOGIA / NEFROLOGIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos