Markers of Hypoxia Correlate with Histologic and Endoscopic Severity of Colitis in Inflammatory Bowel Disease

References

• Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46–54. doi:10.1053/j.gastro.2011.10.001
   PubMed Web of Science ®Google Scholar
• Park KT, Bass D. Inflammatory bowel disease-attributable costs and cost-effective strategies in the United States: a review. Inflamm Bowel Dis. 2011;17(7):1603–1609. doi:10.1002/ibd.21488
   PubMed Web of Science ®Google Scholar
• Froslie KF, Jahnsen J, Moum BA, Vatn MH. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133(2):412–422. doi:10.1053/j.gastro.2007.05.051
   PubMed Web of Science ®Google Scholar
• Laharie D, Filippi J, Roblin X, et al. Impact of mucosal healing on long-term outcomes in ulcerative colitis treated with infliximab: a multicenter experience. Aliment Pharmacol Ther. 2013;37(10):998–1004. doi:10.1111/apt.2013.37.issue-10
   PubMed Web of Science ®Google Scholar
• Travis SP, Higgins PD, Orchard T, et al. Review article: defining remission in ulcerative colitis. Aliment Pharmacol Ther. 2011;34(2):113–124. doi:10.1111/j.1365-2036.2011.04701.x
   PubMed Web of Science ®Google Scholar
• Zenlea T, Yee EU, Rosenberg L, et al. Histology grade is independently associated with relapse risk in patients with ulcerative colitis in clinical remission: a prospective study. Am J Gastroenterol. 2016;111(5):685–690. doi:10.1038/ajg.2016.50
   PubMed Web of Science ®Google Scholar
• Abraham C, Cho JH. Inflammatory bowel disease. N Eng J Med. 2009;361:2066–2076. doi:10.1056/NEJMra0804647
   PubMed Web of Science ®Google Scholar
• Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307–317. doi:10.1038/nature10209
   PubMed Web of Science ®Google Scholar
• Glover LE, Colgan SP. Hypoxia and metabolic factors that influence inflammatory bowel disease pathogenesis. Gastroenterology. 2011;140(6):1748–1755. doi:10.1053/j.gastro.2011.01.056
   PubMed Web of Science ®Google Scholar
• Colgan SP, Campbell EL, Kominsky DJ. Hypoxia and mucosal inflammation. Ann Rev Pathol. 2016;11:77–100. doi:10.1146/annurev-pathol-012615-044231
   PubMed Web of Science ®Google Scholar
• Colgan SP, Taylor CT. Hypoxia: an alarm signal during intestinal inflammation. Nat Rev Gastroenterol Hepatol. 2010;7(5):281–287. doi:10.1038/nrgastro.2010.39
   PubMed Web of Science ®Google Scholar
• Kominsky DJ, Campbell EL, Colgan SP. Metabolic shifts in immunity and inflammation. J Immunol. 2010;184(8):4062–4068. doi:10.4049/jimmunol.0903002
   PubMed Web of Science ®Google Scholar
• Hatoum OA, Binion DG, Otterson MF, Gutterman DD. Acquired microvascular dysfunction in inflammatory bowel disease: loss of nitric oxide-mediated vasodilation. Gastroenterology. 2003;125(1):58–69. doi:10.1016/S0016-5085(03)00699-1
   PubMed Web of Science ®Google Scholar
• Hatoum OA, Heidemann J, Binion DG. The intestinal microvasculature as a therapeutic target in inflammatory bowel disease. Ann N Y Acad Sci. 2006;1072:78–97. doi:10.1196/annals.1326.003
   PubMed Web of Science ®Google Scholar
• Karhausen J, Furuta GT, Tomaszewski JE, Johnson RS, Colgan SP, Haase VH. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest. 2004;114(8):1098–1106. doi:10.1172/JCI200421086
   PubMed Web of Science ®Google Scholar
• Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda). 2009;24:97–106. doi:10.1152/physiol.00045.2008
   PubMed Web of Science ®Google Scholar
• Ratcliffe PJ. HIF-1 and HIF-2: working alone or together in hypoxia? J Clin Invest. 2007;117(4):862–865. doi:10.1172/JCI31750
   PubMed Web of Science ®Google Scholar
• Shah YM, Ito S, Morimura K, et al. Hypoxia-inducible factor augments experimental colitis through an MIF-dependent inflammatory signaling cascade. Gastroenterology. 2008;134(7):2036–2048. doi:10.1053/j.gastro.2008.03.009
   PubMed Web of Science ®Google Scholar
• Giatromanolaki A, Sivridis E, Maltezos E, et al. Hypoxia inducible factor 1alpha and 2alpha overexpression in inflammatory bowel disease. J Clin Pathol. 2003;56(3):209–213. doi:10.1136/jcp.56.3.209
   PubMed Web of Science ®Google Scholar
• Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap) – a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381. doi:10.1016/j.jbi.2008.08.010
   PubMed Web of Science ®Google Scholar
• Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317(26):1625–1629. doi:10.1056/NEJM198712243172603
   PubMed Web of Science ®Google Scholar
• Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut. 1998;43(1):29–32. doi:10.1136/gut.43.1.29
   PubMed Web of Science ®Google Scholar
• Guyatt G, Mitchell A, Irvine EJ, et al. A new measure of health status for clinical trials in inflammatory bowel disease. Gastroenterology. 1989;96(3):804–810. doi:10.1016/S0016-5085(89)80080-0
   PubMed Web of Science ®Google Scholar
• Saverymuttu SH, Camilleri M, Rees H, Lavender JP, Hodgson HJ, Chadwick VS. Indium 111- granulocyte scanning in the assessment of disease extent and disease activity in inflammatory bowel disease. A comparison with colonoscopy, histology, and fecal indium 111-granulocyte excretion. Gastroenterology. 1986;90(5 Pt 1):1121–1128. doi:10.1016/0016-5085(86)90376-8
   PubMed Web of Science ®Google Scholar
• MacManus CF, Campbell EL, Keely S, Burgess A, Kominsky DJ, Colgan SP. Anti-inflammatory actions of adrenomedullin through fine tuning of HIF stabilization. FASEB J. 2011;25(6):1856–1864. doi:10.1096/fj.10-170316
   PubMed Web of Science ®Google Scholar
• Bousvaros A, Leichtner A, Zurakowski D, et al. Elevated serum vascular endothelial growth factor in children and young adults with Crohn’s disease. Dig Dis Sci. 1999;44(2):424–430. doi:10.1023/A:1026635308127
   PubMed Web of Science ®Google Scholar
• Grund B, Sabin C. Analysis of biomarker data: logs, odds ratios, and receiver operating characteristic curves. Curr. 2010;5(6):473–479.
   Google Scholar
• Bosco MC, Delfino S, Ferlito F, et al. Hypoxic synovial environment and expression of macrophage inflammatory protein 3gamma/CCL20 in juvenile idiopathic arthritis. Arthritis Rheum. 2008;58(6):1833–1838. doi:10.1002/art.23516
   PubMedGoogle Scholar
• Bosco MC, Puppo M, Santangelo C, et al. Hypoxia modifies the transcriptome of primary human monocytes: modulation of novel immune-related genes and identification of CC-chemokine ligand 20 as a new hypoxia-inducible gene. J Immunol. 2006;177(3):1941–1955. doi:10.4049/jimmunol.177.3.1941
   PubMed Web of Science ®Google Scholar
• Martin-Rendon E, Hale SJ, Ryan D, et al. Transcriptional profiling of human cord blood CD133+ and cultured bone marrow mesenchymal stem cells in response to hypoxia. Stem Cells. 2007;25(4):1003–1012. doi:10.1634/stemcells.2006-0398
   PubMed Web of Science ®Google Scholar
• Ye LY, Chen W, Bai XL, et al. Hypoxia-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma induces an immunosuppressive tumor microenvironment to promote metastasis. Cancer Res. 2016;76(4):818–830. doi:10.1158/0008-5472.CAN-15-0977
   PubMed Web of Science ®Google Scholar
• Matchar DB, Orlando LA. The relationship between test and outcome. In: Price CP, editor. Evidence-Based Laboratory Medicine; Principles, Practice and Outcomes. Washington DC: AACC Press; 2007:53–66.
   Google Scholar
• Cosin-Roger J, Simmen S, Melhem H, et al. Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation. Nat Commun. 2017;8(1):98. doi:10.1038/s41467-017-00213-3
   PubMedGoogle Scholar
• Kaser A, Ludwiczek O, Holzmann S, et al. Increased expression of CCL20 in human inflammatory bowel disease. J Clin Immunol. 2004;24(1):74–85. doi:10.1023/B:JOCI.0000018066.46279.6b
   PubMed Web of Science ®Google Scholar
• Kwon JH, Keates S, Bassani L, Mayer LF, Keates AC. Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease. Gut. 2002;51(6):818–826. doi:10.1136/gut.51.6.818
   PubMed Web of Science ®Google Scholar
• Lee HJ, Choi SC, Lee MH, et al. Increased expression of MIP-3alpha/CCL20 in peripheral blood mononuclear cells from patients with ulcerative colitis and its down-regulation by sulfasalazine and glucocorticoid treatment. Inflamm Bowel Dis. 2005;11(12):1070–1079. doi:10.1097/01.MIB.0000187576.26043.ac
   PubMed Web of Science ®Google Scholar
• Skovdahl HK, Granlund A, Ostvik AE, et al. Expression of CCL20 and its corresponding receptor CCR6 is enhanced in active inflammatory bowel disease, and TLR3 mediates CCL20 expression in colonic epithelial cells. PLoS ONE. 2015;10(11):e0141710. doi:10.1371/journal.pone.0141710
   PubMed Web of Science ®Google Scholar
• Fujiie S, Hieshima K, Izawa D, et al. Proinflammatory cytokines induce liver and activation- regulated chemokine/macrophage inflammatory protein-3alpha/CCL20 in mucosal epithelial cells through NF-kappaB [correction of NK-kappaB]. Int Immunol. 2001;13(10):1255–1263. doi:10.1093/intimm/13.10.1255
   PubMed Web of Science ®Google Scholar
• Maxwell PH, Eckardt KU. HIF prolyl hydroxylase inhibitors for the treatment of renal anaemia and beyond. Nat Rev Nephrol. 2016;12(3):157–168. doi:10.1038/nrneph.2015.193
   PubMed Web of Science ®Google Scholar
• Katsanos KH, Tatsioni A, Natsi D, Sigounas D, Christodoulou DK, Tsianos EV. Recombinant human erythropoietin in patients with inflammatory bowel disease and refractory anemia: a 15-year single center experience. J Crohns Colitis. 2012;6(1):56–61. doi:10.1016/j.crohns.2011.07.004
   PubMed Web of Science ®Google Scholar
• Liu S, Ren J, Hong Z, et al. Efficacy of erythropoietin combined with enteral nutrition for the treatment of anemia in Crohn’s disease: a prospective cohort study. Nutr Clin Pract. 2013;28(1):120–127. doi:10.1177/0884533612462744
   PubMed Web of Science ®Google Scholar
• Kapsoritakis AN, Psychos AK, Sfiridaki A, Zintzaras E, Potamianos SP. Finger clubbing and erythropoietin serum levels in active IBD. Inflamm Bowel Dis. 2006;12(6):535–536. doi:10.1097/00054725-200606000-00014
   PubMed Web of Science ®Google Scholar
• Tsitsika A, Stamoulakatou A, Kafritsa Y, et al. Erythropoietin levels in children and adolescents with inflammatory bowel disease. J Pediatr Hematol Oncol. 2005;27(2):93–96. doi:10.1097/01.mph.0000153441.34407.d9
   PubMed Web of Science ®Google Scholar
• Brothers MD, Doan BK, Zupan MF, Wile AL, Wilber RL, Byrnes WC. Hematological and physiological adaptations following 46 weeks of moderate altitude residence. High Alt Med Biol. 2010;11(3):199–208.s. doi:10.1089/ham.2009.1090
   PubMed Web of Science ®Google Scholar
• Ferrante M, Pierik M, Henckaerts L, et al. The role of vascular endothelial growth factor (VEGF) in inflammatory bowel disease. Inflamm Bowel Dis. 2006;12(9):870–878. doi:10.1097/01.mib.0000235095.01608.10
   PubMed Web of Science ®Google Scholar
• Magro F, Araujo F, Pereira P, Meireles E, Diniz-Ribeiro M, Velosom FT. Soluble selectins, sICAM, sVCAM, and angiogenic proteins in different activity groups of patients with inflammatory bowel disease. Dig Dis Sci. 2004;49(7–8):1265–1274. doi:10.1023/B:DDAS.0000037822.55717.31
   PubMed Web of Science ®Google Scholar
• Pousa ID, Mate J, Salcedo-Mora X, Abreu MT, Moreno-Otero R, Gisbert JP. Role of vascular endothelial growth factor and angiopoietin systems in serum of Crohn’s disease patients. Inflamm Bowel Dis. 2008;14(1):61–67. doi:10.1002/ibd.20269
   PubMed Web of Science ®Google Scholar
• Scaldaferri F, Vetrano S, Sans M, et al. VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology. 2009;136(2):585–595. doi:10.1053/j.gastro.2008.09.064
   PubMed Web of Science ®Google Scholar
• Griga T, Voigt E, Gretzer B, Brasch F, May B. Increased production of vascular endothelial growth factor by intestinal mucosa of patients with inflammatory bowel disease. Hepatogastroenterology. 1999;46(26):920–923.
   PubMedGoogle Scholar
• Griga T, Tromm A, Spranger J, May B. Increased serum levels of vascular endothelial growth factor in patients with inflammatory bowel disease. Scand J Gastroenterol. 1998;33(5):504–508. doi:10.1080/00365529850172070
   PubMed Web of Science ®Google Scholar
• Cummins EP, Seeballuck F, Keely SJ, et al. The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology. 2008;134(1):156–165. doi:10.1053/j.gastro.2007.10.012
   PubMed Web of Science ®Google Scholar
• Fraisl P, Aragones J, Carmeliet P. Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat Rev Drug Discov. 2009;8(2):139–152. doi:10.1038/nrd2761
   PubMed Web of Science ®Google Scholar
• Taylor CT, Colgan SP. Hypoxia and gastrointestinal disease. J Mol Med. 2007;85(12):1295–1300. doi:10.1007/s00109-007-0277-z
   PubMed Web of Science ®Google Scholar
• Tambuwala MM, Manresa MC, Cummins EP, Aversa V, Coulter IS, Taylor CT. Targeted delivery of the hydroxylase inhibitor DMOG provides enhanced efficacy with reduced systemic exposure in a murine model of colitis. J Control Release. 2015;217:221–227. doi:10.1016/j.jconrel.2015.09.022
   PubMed Web of Science ®Google Scholar