TY - JOUR
T1 - 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
AU - Misra, Sanjay
AU - Shergill, Uday
AU - Yang, Binxia
AU - Janardhanan, Rajiv
AU - Misra, Khamal D.
N1 - Funding Information:
The project described was supported by Award Number R01HL098967 (to S.M.) from the National Heart, Lung, And Blood Institute and a CR20 grant, which is funded by 1UL1RR024150 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, And Blood Institute or the National Institutes of Health. None of the other authors have identified a conflict of interest.
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - ADAMTS-1
KW - AVF
KW - ESRD
KW - HIF-1α
KW - MMP-2
KW - PTFE
KW - RT-PCR
KW - TIMP-1,-2
KW - VEGF-A
KW - a disintegrin and metalloproteinase thrombospondin-1
KW - arteriovenous fistula
KW - end-stage renal disease
KW - hypoxia inducible factor-1 alpha
KW - matrix metalloproteinase-2
KW - polytetrafluoroethylene
KW - realtime polymerase chain reaction
KW - tissue inhibitor of metalloproteinase-1,-2
KW - vascular endothelial growth factor-A
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U2 - 10.1016/j.jvir.2010.02.043
DO - 10.1016/j.jvir.2010.02.043
M3 - Article
C2 - 20598569
AN - SCOPUS:77955716422
SN - 1051-0443
VL - 21
SP - 1255
EP - 1261
JO - Journal of Vascular and Interventional Radiology
JF - Journal of Vascular and Interventional Radiology
IS - 8
ER -