Abstract
Deregulated angiogenesis is a major underlying cause of many severe diseases including cancer, retinopathy, diabetes, myocardial infarction, and stroke. In these diseases, tissue hypoxia is the main cause of the pathological vascular phenotypes. While the mechanisms behind hypoxia-induced changes in cellular signaling have been extensively studied in vitro, much less is known regarding the effects of hypoxia in physiological or pathological settings in vivo. The highly hypoxia-tolerant zebrafish and glass catfish provide excellent systems for studying the effects of hypoxia on angiogenesis and vascular pathology in vertebrate disease models. Here we present and discuss the benefits and drawbacks in using zebrafish to study basic mechanisms of hypoxia in disease, with special emphasis on the role of angiogenesis and vascular function. Specifically, we will in detail discuss zebrafish models of hypoxia-induced angiogenesis in the retina and tumor, as well as acute hypoxia models using glass catfish, and discuss the usefulness of these models to elucidate key mechanisms behind pathological vascular disruption in retinopathy and cancer. At the end of the chapter we contextualize the hypoxia-induced angiogenesis-mediated zebrafish disease models and discuss the perspectives in using zebrafish for medical research on hypoxia and angiogenesis.
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References
Jensen LD, Rouhi P, Cao Z, Lanne T, Wahlberg E, Cao Y (2011) Zebrafish models to study hypoxia-induced pathological angiogenesis in malignant and nonmalignant diseases. Birth Defects Res Part C Embryo Today 93:182–193
Rouhi P, Jensen LD, Cao Z, Hosaka K, Lanne T, Wahlberg E, Steffensen JF, Cao Y (2010) Hypoxia-induced metastasis model in embryonic zebrafish. Nat Protoc 5:1911–1918
Cao Z, Jensen LD, Rouhi P, Hosaka K, Lanne T, Steffensen JF, Wahlberg E, Cao Y (2010) Hypoxia-induced retinopathy model in adult zebrafish. Nat Protoc 5:1903–1910
Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186
Ferrara N (2010) Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy. Nat Med 16:1107–1111
Cao R, Jensen LD, Soll I, Hauptmann G, Cao Y (2008) Hypoxia-induced retinal angiogenesis in zebrafish as a model to study retinopathy. PLoS One 3:e2748
Lee SL, Rouhi P, Dahl Jensen L, Zhang D, Ji H, Hauptmann G, Ingham P, Cao Y (2009) Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model. Proc Natl Acad Sci USA 106:19485–19490
Makino Y, Cao R, Svensson K, Bertilsson G, Asman M, Tanaka H, Cao Y, Berkenstam A, Poellinger L (2001) Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 414:550–554
Cao Y (2011) Antiangiogenic cancer therapy: why do mouse and human patients respond in a different way to the same drug? Int J Dev Biol 55:557–562
Folk JC, Stone EM (2010) Ranibizumab therapy for neovascular age-related macular degeneration. N Engl J Med 363:1648–1655
Zhang D, Hedlund EM, Lim S, Chen F, Zhang Y, Sun B, Cao Y (2011) Antiangiogenic agents significantly improve survival in tumor-bearing mice by increasing tolerance to chemotherapy-induced toxicity. Proc Natl Acad Sci USA 108:4117–4122
Kamba T, McDonald DM (2007) Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer 96:1788–1795
Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8:592–603
Jensen LD, Cao Y (2013) Clock controls angiogenesis. Cell Cycle 12:405–408
Jensen LD, Cao Z, Nakamura M, Yang Y, Brautigam L, Andersson P, Zhang Y, Wahlberg E, Lanne T, Hosaka K, Cao Y (2012) Opposing effects of circadian clock genes bmal1 and period2 in regulation of VEGF-dependent angiogenesis in developing zebrafish. Cell Rep 2:231–241
Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty KE, Lawson ND (2010) MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature 464:1196–1200
Semenza GL (2012) Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci 33:207–214
Bailey KM, Wojtkowiak JW, Hashim AI, Gillies RJ (2012) Targeting the metabolic microenvironment of tumors. Adv Pharmacol 65:63–107
Keith B, Simon MC (2007) Hypoxia-inducible factors, stem cells, and cancer. Cell 129:465–472
Dang CV (2012) Links between metabolism and cancer. Genes Dev 26:877–890
Warburg O (1956) On the origin of cancer cells. Science 123:309–314
Peterson RT, Shaw SY, Peterson TA, Milan DJ, Zhong TP, Schreiber SL, MacRae CA, Fishman MC (2004) Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation. Nat Biotechnol 22:595–599
Antonetti DA, Klein R, Gardner TW (2012) Diabetic retinopathy. N Engl J Med 366:1227–1239
Chen J, Smith LE (2007) Retinopathy of prematurity. Angiogenesis 10:133–140
Dahl Ejby Jensen L, Cao R, Hedlund EM, Soll I, Lundberg JO, Hauptmann G, Steffensen JF, Cao Y (2009) Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish. Proc Natl Acad Sci USA 106:18408–18413
Yaniv K, Isogai S, Castranova D, Dye L, Hitomi J, Weinstein BM (2006) Live imaging of lymphatic development in the zebrafish. Nat Med 12:711–716
Kuchler AM, Gjini E, Peterson-Maduro J, Cancilla B, Wolburg H, Schulte-Merker S (2006) Development of the zebrafish lymphatic system requires VEGFC signaling. Curr Biol 16:1244–1248
Rasmussen KJ, Steffensen JF, Buchmann K (2013) Differential occurrence of immune cells in the primary and secondary vascular systems in rainbow trout, Oncorhynchus mykiss (Walbaum). J Fish Dis 36:675–679
Robichaux JL, Tanno E, Rappleye JW, Ceballos M, Stallcup WB, Schmid-Schonbein GW, Murfee WL (2010) Lymphatic/Blood endothelial cell connections at the capillary level in adult rat mesentery. Anat Rec (Hoboken) 293:1629–1638
Hogan BM, Bos FL, Bussmann J, Witte M, Chi NC, Duckers HJ, Schulte-Merker S (2009) Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat Genet 41:396–398
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Jensen, L.D., Rouhi, P., Cao, Y. (2013). Hypoxia-Induced Pathological Angiogenesis in Zebrafish. In: Dulak, J., Józkowicz, A., Łoboda, A. (eds) Angiogenesis and Vascularisation. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1428-5_13
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DOI: https://doi.org/10.1007/978-3-7091-1428-5_13
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