Document Detail

Expression of hypoxia inducible factor-1 alpha, macrophage migration inhibition factor, matrix metalloproteinase-2 and -9, and their inhibitors in hemodialysis grafts and arteriovenous fistulas.
MedLine Citation:
PMID:  18341958     Owner:  NLM     Status:  MEDLINE    
PURPOSE: It is well recognized that arteriovenous fistulas (AVFs) used for hemodialysis access have better primary patency rates with less restenosis than polytetrafluoroethylene (PTFE) grafts; however, the mechanism responsible for this is not known. Recent data suggest that hypoxia inducible factor-1 alpha (HIF-1 alpha) is associated with vascular restenosis, possibly through mechanisms that increase the production of macrophage migration inhibition factor (MIF), matrix metalloproteinase-2 (MMP-2) and MMP-9, and their inhibitors (tissue inhibitor of MMPs; TIMP). The present study tested the hypothesis that there are differences in the expression patterns of HIF-1 alpha, MIF, MMP-2, MMP-9, and TIMPs in specimens removed from patients with AVFs and PTFE grafts.
MATERIALS AND METHODS: Whole-vessel tissue samples were obtained from the vein distal to the vein-to-PTFE graft anastomosis and the proximal outflow vein (within 6 cm of the arteriovenous anastomosis) of AVFs from 17 patients who required a surgical revision for thrombosis and stenosis. Nonstenotic veins of four patients undergoing hemodialysis vascular access placement were used as controls. PTFE grafts (n = 6), AVFs (n = 6), and control samples (n = 3) underwent Western blot analysis and zymography. A separate group of five patients with PTFE hemodialysis grafts and one control subject were used for immunohistochemical analysis.
RESULTS: Specimens from patients with PTFE grafts had significantly higher expression of HIF-1 alpha (P = .03), MIF (P = .02), TIMP-1 (P = .0006), pro-MMP-2 (P = .02), and pro-MMP-9 (P = .046) compared with control veins. The expression of only pro-MMP-9 was significantly higher in AVFs compared with control samples (P = .004). There was a significant increase in the expression of MIF (P = .007) and TIMP-1 (P < .0001) in PTFE graft specimens compared with AVFs. MIF and TIMP-1 were localized to the adventitia of the vein distal to the vein-to-PTFE graft anastomosis.
CONCLUSIONS: There were major differences in the expression patterns of hypoxia (ie, HIF-1 alpha) and proteins regulated by HIF-1?, including MIF, pro-MMP-2, pro-MMP-9, and TIMP-1, in specimens removed from patients with PTFE grafts and AVFs. Understanding the role of HIF-1 alpha and these proteins in hemodialysis access failure can help improve outcomes.
Sanjay Misra; Alex A Fu; Dheeraj K Rajan; Luis A Juncos; Michael A McKusick; Haraldur Bjarnason; Debabrata Mukhopadhyay
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of vascular and interventional radiology : JVIR     Volume:  19     ISSN:  1051-0443     ISO Abbreviation:  J Vasc Interv Radiol     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-03-17     Completed Date:  2008-05-13     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  9203369     Medline TA:  J Vasc Interv Radiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  252-9     Citation Subset:  IM    
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MeSH Terms
Arteriovenous Shunt, Surgical*
Blotting, Western
Graft Occlusion, Vascular / metabolism*
Hypoxia-Inducible Factor 1 / metabolism*
Macrophage Migration-Inhibitory Factors / metabolism*
Matrix Metalloproteinase 2 / metabolism*
Matrix Metalloproteinase 9 / metabolism*
Middle Aged
Renal Dialysis*
Grant Support
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1; 0/Macrophage Migration-Inhibitory Factors; 9002-84-0/Polytetrafluoroethylene; EC Metalloproteinase 2; EC Metalloproteinase 9

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