Increased expression of HIF-1α, VEGF-A and its receptors, MMP-2, TIMP-1, and ADAMTS-1 at the venous stenosis of arteriovenous fistula in a mouse model with renal insufficiency

Sanjay Misra, Uday Shergill, Binxia Yang, Rajiv Janardhanan, Khamal D. Misra

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

PURPOSE: A mouse model of renal insufficiency with arteriovenous fistula (AVF) and venous stenosis was created. The authors tested the hypothesis that there is increased gene expression of hypoxia-inducible factor-1 alpha (HIF-1α); vascular endothelial growth factor-A (VEGF-A) and its receptors (VEGFR-1,-2); matrix metalloproteinase-2 (MMP-2),-9 (MMP-9); tissue inhibitor of metalloproteinase-1,-2 (TIMP-1,-2); and a disintegrin and metalloproteinase thrombospondin-1 (ADAMTS-1) at the venous stenosis. MATERIALS AND METHODS: Nineteen male C57BL/6 mice underwent a left nephrectomy and a surgical occlusion of the right upper pole to induce renal function characterized in eight animals. Twenty eight days later, an AVF (n = 11) was created from the right carotid artery to ipsilateral jugular vein, and the mice were killed at day 7 (n = 4) and day 14 (n = 4). The outflow and control veins were removed for gene expression. Three mice were killed at day 28 for histologic analysis. RESULTS: The mean serum blood urea nitrogen level remained significantly elevated for 8 weeks when compared with baseline (P <.05). By day seven, there was a significant increase in the expression of HIF-1α, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein, with HIF-1α and TIMP-1 levels significantly elevated at day 14 (P <.05). By day 28, the venous stenosis was characterized by a thickened vein wall and neointima. CONCLUSIONS: A mouse model of renal insufficiency with AVF was developed that had increased expression of HIF-1α, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein with venous stenosis by day 28.

Original languageEnglish (US)
Pages (from-to)1255-1261
Number of pages7
JournalJournal of Vascular and Interventional Radiology
Volume21
Issue number8
DOIs
StatePublished - 2010

Keywords

  • ADAMTS-1
  • AVF
  • ESRD
  • HIF-1α
  • MMP-2
  • PTFE
  • RT-PCR
  • TIMP-1,-2
  • VEGF-A
  • a disintegrin and metalloproteinase thrombospondin-1
  • arteriovenous fistula
  • end-stage renal disease
  • hypoxia inducible factor-1 alpha
  • matrix metalloproteinase-2
  • polytetrafluoroethylene
  • realtime polymerase chain reaction
  • tissue inhibitor of metalloproteinase-1,-2
  • vascular endothelial growth factor-A

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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