| Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts. | |
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MedLine Citation:
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PMID: 18326810 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Venous injury and subsequent venous stenosis formation are responsible for hemodialysis graft failure. Our hypothesis is that these pathological changes are in part related to changes in wall shear stress (WSS) that results in the activation of matrix regulatory proteins causing subsequent venous stenosis formation. In the present study, we examined the serial changes in WSS, blood flow, and luminal vessel area that occur subsequent to the placement of a hemodialysis graft in a porcine model of chronic renal insufficiency. We then determined the corresponding histological, morphometric, and kinetic changes of several matrix regulatory proteins including VEGF-A, its receptors, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and TIMP-2. WSS was estimated by obtaining blood flow and luminal vessel area by performing phase-contrast MRI with magnetic resonance angiography in 21 animals at 1 day after graft placement and prior to death on day 3 (n = 7), day 7 (n = 7), and day 14 (n = 7). At all time points, the mean WSS at the vein-to-graft anastomosis was significantly higher than that at the control vein (P < 0.05). WSS had a bimodal distribution with peaks on days 1 and 7 followed by a significant reduction in WSS by day 14 (P < 0.05 compared with day 7) and a decrease in luminal vessel area compared with control vessels. By day 3, there was a significant increase in VEGF-A and pro-MMP-9 followed by, on day 7, increased pro-MMP-2, active MMP-2, and VEGF receptor (VEGFR)-2 (P < 0.05) and, by day 14, increased VEGFR-1 and TIMP-1 (P < 0.05) at the vein-to-graft anastomosis compared with control vessels. Over time, the neointima thickened and was composed primarily of alpha-smooth muscle actin-positive cells with increased cellular proliferation. Our data suggest that hemodialysis graft placement leads to early increases in WSS, VEGF-A, and pro-MMP-9 followed by subsequent increases in pro-MMP-2, active MMP-2, VEGFR-1, VEGFR-2, and TIMP-1, which may contribute to the development of venous stenosis. |
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Authors:
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Sanjay Misra; Alex A Fu; Alessandra Puggioni; Kamran M Karimi; Jaywant N Mandrekar; James F Glockner; Luis A Juncos; Bilal Anwer; Antonio M McGuire; Debabrata Mukhopadhyay |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-03-07 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 294 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-05-07 Completed Date: 2008-06-12 Revised Date: 2011-06-06 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2219-30 Citation Subset: IM |
Affiliation:
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Department of Radiology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. misra.sanjay@mayo.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arteriovenous Shunt, Surgical / adverse effects*, instrumentation Blood Vessel Prosthesis Blood Vessel Prosthesis Implantation / adverse effects Collagenases / metabolism* Constriction, Pathologic Disease Models, Animal Graft Occlusion, Vascular / etiology, metabolism*, pathology, physiopathology Jugular Veins / metabolism*, pathology, physiopathology Magnetic Resonance Angiography Male Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / metabolism Polytetrafluoroethylene Prosthesis Design Receptors, Vascular Endothelial Growth Factor / metabolism* Regional Blood Flow Renal Dialysis* Renal Insufficiency, Chronic / metabolism, therapy Stress, Mechanical Sus scrofa Time Factors Tissue Inhibitor of Metalloproteinase-1 / metabolism* Up-Regulation Vascular Endothelial Growth Factor A / metabolism* Vascular Endothelial Growth Factor Receptor-1 / metabolism Vascular Endothelial Growth Factor Receptor-2 / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA 78383/CA/NCI NIH HHS; HL 072178/HL/NHLBI NIH HHS; HL 70567/HL/NHLBI NIH HHS; R01 DK073401-05/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Tissue Inhibitor of Metalloproteinase-1; 0/Vascular Endothelial Growth Factor A; 9002-84-0/Polytetrafluoroethylene; EC 2.7.10.1/Receptors, Vascular Endothelial Growth Factor; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2; EC 3.4.24.-/Collagenases; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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