PMID- 28163173 OWN - NLM STAT- MEDLINE DCOM- 20171212 LR - 20240213 IS - 1615-5947 (Electronic) IS - 0890-5096 (Print) IS - 0890-5096 (Linking) VI - 41 DP - 2017 May TI - Increased Oxidative Stress and Hypoxia Inducible Factor-1 Expression during Arteriovenous Fistula Maturation. PG - 225-234 LID - S0890-5096(17)30105-X [pii] LID - 10.1016/j.avsg.2016.09.014 [doi] AB - BACKGROUND: The poor clinical results that are frequently reported for arteriovenous fistulae (AVF) for hemodialysis are typically due to failure of AVF maturation. We hypothesized that early AVF maturation is associated with generation of reactive oxygen species and activation of the hypoxia-inducible factor-1 (HIF-1) pathway, potentially promoting neointimal hyperplasia. We tested this hypothesis using a previously reported mouse AVF model that recapitulates human AVF maturation. METHODS: Aortocaval fistulae were created in C57Bl/6 mice and compared with sham-operated mice. AVFs or inferior vena cavas were analyzed using a microarray, Amplex Red for extracellular H(2)O(2), quantitative polymerase chain reaction, immunohistochemistry, and immunoblotting for HIF-1alpha and immunofluorescence for NOX-2, nitrotyrosine, heme oxygenase-1 (HO-1), and vascular endothelial growth factor (VEGF)-A. RESULTS: Oxidative stress was higher in AVF than that in control veins, with more H(2)O(2) (P = 0.007) and enhanced nitrotyrosine immunostaining (P = 0.005). Immunohistochemistry and immunoblot showed increased HIF-1alpha immunoreactivity in the AVF endothelium; HIF-1 targets NOX-2, HO-1 and VEGF-A were overexpressed in the AVF (P < 0.01). AVF expressed increased numbers of HIF-1alpha (P < 0.0001) and HO-1 (P < 0.0001) messenger RNA transcripts. CONCLUSIONS: Oxidative stress increases in mouse AVF during early maturation, with increased expression of HIF-1alpha and its target genes NOX-2, HO-1, and VEGF-A. These results suggest that clinical strategies to improve AVF maturation could target the HIF-1 pathway. CI - Published by Elsevier Inc. FAU - Sadaghianloo, Nirvana AU - Sadaghianloo N AD - Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, University Hospital of Nice-Sophia Antipolis, Nice, France. Electronic address: sadaghianloo.n@chu-nice.fr. FAU - Yamamoto, Kota AU - Yamamoto K AD - Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT; Department of Surgery, Yale University School of Medicine, New Haven, CT; Division of Vascular Surgery, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Bai, Hualong AU - Bai H AD - Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT; Department of Vascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China. FAU - Tsuneki, Masayuki AU - Tsuneki M AD - National Cancer Center Research Institute, Tokyo, Japan; Department of Pathology, Yale University School of Medicine, New Haven, CT. FAU - Protack, Clinton D AU - Protack CD AD - Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT; Department of Surgery, Yale University School of Medicine, New Haven, CT. FAU - Hall, Michael R AU - Hall MR AD - Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT; Department of Surgery, Yale University School of Medicine, New Haven, CT. FAU - Declemy, Serge AU - Declemy S AD - Department of Vascular Surgery, University Hospital of Nice-Sophia Antipolis, Nice, France. FAU - Hassen-Khodja, Reda AU - Hassen-Khodja R AD - Department of Vascular Surgery, University Hospital of Nice-Sophia Antipolis, Nice, France. FAU - Madri, Joseph AU - Madri J AD - Department of Pathology, Yale University School of Medicine, New Haven, CT. FAU - Dardik, Alan AU - Dardik A AD - Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT; Department of Surgery, Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare Systems, West Haven, CT. LA - eng GR - P01 NS062686/NS/NINDS NIH HHS/United States GR - R01 HL095498/HL/NHLBI NIH HHS/United States GR - R01 HL127386/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20170203 PL - Netherlands TA - Ann Vasc Surg JT - Annals of vascular surgery JID - 8703941 RN - 0 (Hif1a protein, mouse) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Membrane Proteins) RN - 0 (Reactive Oxygen Species) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, mouse) RN - 3604-79-3 (3-nitrotyrosine) RN - 42HK56048U (Tyrosine) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (Hmox1 protein, mouse) RN - EC 1.6.3.- (Cybb protein, mouse) RN - EC 1.6.3.- (NADPH Oxidase 2) SB - IM MH - Animals MH - Aorta/metabolism/pathology/physiopathology/*surgery MH - *Arteriovenous Shunt, Surgical/adverse effects MH - Gene Expression Regulation MH - Heme Oxygenase-1/genetics/metabolism MH - Hydrogen Peroxide/metabolism MH - Hyperplasia MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism MH - Male MH - Membrane Proteins/genetics/metabolism MH - Mice, Inbred C57BL MH - NADPH Oxidase 2/metabolism MH - Neointima MH - *Oxidative Stress MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction MH - Time Factors MH - Tyrosine/analogs & derivatives/metabolism MH - Vascular Endothelial Growth Factor A/genetics/metabolism MH - Vascular Patency MH - Vena Cava, Inferior/metabolism/pathology/physiopathology/*surgery PMC - PMC5411319 MID - NIHMS849230 EDAT- 2017/02/07 06:00 MHDA- 2017/12/13 06:00 PMCR- 2018/05/01 CRDT- 2017/02/07 06:00 PHST- 2016/07/19 00:00 [received] PHST- 2016/09/19 00:00 [revised] PHST- 2016/09/19 00:00 [accepted] PHST- 2017/02/07 06:00 [pubmed] PHST- 2017/12/13 06:00 [medline] PHST- 2017/02/07 06:00 [entrez] PHST- 2018/05/01 00:00 [pmc-release] AID - S0890-5096(17)30105-X [pii] AID - 10.1016/j.avsg.2016.09.014 [doi] PST - ppublish SO - Ann Vasc Surg. 2017 May;41:225-234. doi: 10.1016/j.avsg.2016.09.014. Epub 2017 Feb 3.