Abstract
Sprouting angiogenesis by endothelial cells is the main mechanism of new vessel formation in fetal development and in postnatal disease, where either exaggerated (e.g., in cancer, inflammation, and eye diseases) or inadequate vessel growth (e.g., in ischemic diseases like stroke, myocardial infarction, or neurodegeneration) drives the progression of pathology. Endothelial cells receive signals (such as hypoxia, growth factors, or mechanical cues) from the tissue environment and respond by adjusting sprouting angiogenesis and related processes like the adhesion of inflammatory cells, the permeability of intercellular junction, or cellular differentiation in order to maintain tissue homeostasis. Endothelial transcription factors are located at a strategically important nexus to control the expression of specific gene groups and thereby coordinate the endothelial responses to external stimuli. We review here mainly evidence from studies in model organisms (especially mice and zebrafish) regarding the function of pro- and anti-angiogenic transcription factors, their important target genes, and how they are regulated by upstream cytosolic signaling pathways.
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References
Accili D, Arden KC (2004) FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 117:421–426
Ali F, Hamdulay SS, Kinderlerer AR et al (2007) Statin-mediated cytoprotection of human vascular endothelial cells: a role for Kruppel-like factor 2-dependent induction of heme oxygenase-1. J Thromb Haemost 5:2537–2546. https://doi.org/10.1111/j.1538-7836.2007.02787.x
Anderson JD, Johansson HJ, Graham CS et al (2016) Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-KappaB signaling. Stem Cells 34:601–613. https://doi.org/10.1002/stem.2298
Arden KC (2008) FOXO animal models reveal a variety of diverse roles for FOXO transcription factors. Oncogene 27:2345–2350. https://doi.org/10.1038/onc.2008.27
Asano Y, Stawski L, Hant F et al (2010) Endothelial Fli1 deficiency impairs vascular homeostasis: a role in scleroderma vasculopathy. Am J Pathol 176:1983–1998. https://doi.org/10.2353/ajpath.2010.090593
Atkins GB, Wang Y, Mahabeleshwar GH et al (2008) Hemizygous deficiency of Krüppel-like factor 2 augments experimental atherosclerosis. Circ Res 103:690–693. https://doi.org/10.1161/CIRCRESAHA.108.184663
Ausprunk DH, Folkman J (1977) Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 14:53–65
Bach FH, Hancock WW, Ferran C (1997) Protective genes expressed in endothelial cells: a regulatory response to injury. Immunol Today 18:483–486
Baudino TA, Cleveland JL (2001) The Max network gone mad. Mol Cell Biol 21:691–702
Bertout JA, Patel SA, Simon MC (2008) The impact of O2 availability on human cancer. Nat Rev Cancer 8:967–975. https://doi.org/10.1038/nrc2540
Birdsey GM, Shah AV, Dufton N et al (2015) The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling. Dev Cell 32:82–96. https://doi.org/10.1016/j.devcel.2014.11.016
Boon RA, Urbich C, Fischer A et al (2011) Kruppel-like factor 2 improves neovascularization capacity of aged proangiogenic cells. Eur Heart J 32:371–377. https://doi.org/10.1093/eurheartj/ehq137
Brantley DM, Cheng N, Thompson EJ et al (2002) Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene 21:7011–7026. https://doi.org/10.1038/sj.onc.1205679
Carson DA, Lois A (1995) Cancer progression and p53. Lancet (London, England) 346:1009–1011
Carter ME, Brunet A (2007) FOXO transcription factors. Curr Biol 17:R113–R114. https://doi.org/10.1016/j.cub.2007.01.008
Castrillon DH, Miao L, Kollipara R et al (2003) Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science 301:215–218. https://doi.org/10.1126/science.1086336
Chava KR, Tauseef M, Sharma T, Mehta D (2012) Cyclic AMP response element-binding protein prevents endothelial permeability increase through transcriptional controlling p190RhoGAP expression. Blood 119:308–319. https://doi.org/10.1182/blood-2011-02-339473
Chen C, Cai S, Wang G et al (2013) c-Myc enhances colon cancer cell-mediated angiogenesis through the regulation of HIF-1α. Biochem Biophys Res Commun 430:505–511. https://doi.org/10.1016/j.bbrc.2012.12.006
Chien S (2006) Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am J Physiol Heart Circ Physiol 292:H1209–H1224. https://doi.org/10.1152/ajpheart.01047.2006
Chiu J-J, Chien S (2011) Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev 91:327–387. https://doi.org/10.1152/physrev.00047.2009
Choi J, Dong L, Ahn J et al (2007) FoxH1 negatively modulates flk1 gene expression and vascular formation in zebrafish. Dev Biol 304:735–744. https://doi.org/10.1016/j.ydbio.2007.01.023
Collins T, Read MA, Neish AS et al (1995) Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J 9:899–909
Coulon C, Georgiadou M, Roncal C et al (2010) From vessel sprouting to normalization: role of the prolyl hydroxylase domain protein/hypoxia-inducible factor oxygen-sensing machinery. Arterioscler Thromb Vasc Biol 30:2331–2336. https://doi.org/10.1161/ATVBAHA.110.214106
Craig MP, Grajevskaja V, Liao H-K et al (2015) Etv2 and Fli1b function together as key regulators of vasculogenesis and angiogenesis significance. Arterioscler Thromb Vasc Biol 35:865–876. https://doi.org/10.1161/ATVBAHA.114.304768
Dai G, Vaughn S, Zhang Y et al (2007) Biomechanical forces in atherosclerosis-resistant vascular regions regulate endothelial redox balance via phosphoinositol 3-kinase/Akt-dependent activation of Nrf2. Circ Res 101:723–733. https://doi.org/10.1161/CIRCRESAHA.107.152942
Dai X, She P, Chi F et al (2013) Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration, and angiogenesis. J Biol Chem 288:34041–34051. https://doi.org/10.1074/jbc.M113.518019
Dameron KM, Volpert OV, Tainsky MA, Bouck N (1994) Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 265:1582–1584
Dang CV, Eischen CM, Randle DH et al (2012) MYC on the path to cancer. Cell 149:22–35. https://doi.org/10.1016/j.cell.2012.03.003
De Val S, Black BL (2009) Transcriptional control of endothelial cell development. Dev Cell 16:180–195. https://doi.org/10.1016/j.devcel.2009.01.014
De Val S, Chi NC, Meadows SM et al (2008) Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors. Cell 135:1053–1064. https://doi.org/10.1016/j.cell.2008.10.049
Dekker RJ, van Soest S, Fontijn RD et al (2002) Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Krüppel-like factor (KLF2). Blood 100:1689–1698. https://doi.org/10.1182/blood-2002-01-0046
Doddaballapur A, Michalik KM, Manavski Y et al (2015) Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3. Arterioscler Thromb Vasc Biol 35:137–145. https://doi.org/10.1161/ATVBAHA.114.304277
Dohn M, Jiang J, Chen X (2001) Receptor tyrosine kinase EphA2 is regulated by p53-family proteins and induces apoptosis. Oncogene 20:6503–6515. https://doi.org/10.1038/sj.onc.1204816
Donehower LA, Harvey M, Slagle BL et al (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215–221. https://doi.org/10.1038/356215a0
Dong J, Feldmann G, Huang J et al (2007) Elucidation of a universal size-control mechanism in drosophila and mammals. Cell 130:1120–1133. https://doi.org/10.1016/j.cell.2007.07.019
Dube A, Thai S, Gaspar J et al (2001) Elf-1 is a transcriptional regulator of the Tie2 gene during vascular development. Circ Res 88:237–244
Dumont O, Mylroie H, Bauer A et al (2012) Protein kinase Cε activity induces anti-inflammatory and anti-apoptotic genes via an ERK1/2- and NF-κB-dependent pathway to enhance vascular protection. Biochem J 447:193–204. https://doi.org/10.1042/BJ20120574
Ebert BL, Gleadle JM, O’Rourke JF et al (1996) Isoenzyme-specific regulation of genes involved in energy metabolism by hypoxia: similarities with the regulation of erythropoietin. Biochem J 313(Pt 3):809–814
Ema M, Taya S, Yokotani N et al (1997) A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci USA 94:4273–4278
Faviana P, Boldrini L, Spisni R et al (2002) Neoangiogenesis in colon cancer: correlation between vascular density, vascular endothelial growth factor (VEGF) and p53 protein expression. Oncol Rep 9:617–620
Froese N, Kattih B, Breitbart A et al (2011) GATA6 promotes angiogenic function and survival in endothelial cells by suppression of autocrine transforming growth factor β/Activin receptor-like kinase 5 signaling. J Biol Chem 286:5680–5690. https://doi.org/10.1074/jbc.M110.176925
Fu R, Chen Y, Wang X-P et al (2016) Wogonin inhibits multiple myeloma-stimulated angiogenesis via c-Myc/VHL/HIF-1α signaling axis. Oncotarget 7:5715–5727. https://doi.org/10.18632/oncotarget.6796
Fujiwara Y, Browne CP, Cunniff K et al (1996) Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Proc Natl Acad Sci USA 93:12355–12358
Fukasawa M, Tsuchiya T, Takayama E et al (2004) Identification and characterization of the hypoxia-responsive element of the human placental 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene. J Biochem 136:273–277. https://doi.org/10.1093/jb/mvh137
Furuyama T, Kitayama K, Shimoda Y et al (2004) Abnormal angiogenesis in Foxo1 (Fkhr)-deficient mice. J Biol Chem 279:34741–34749. https://doi.org/10.1074/jbc.M314214200
Gao X, Johnson KD, Chang Y-I et al (2013) Gata2 cis-element is required for hematopoietic stem cell generation in the mammalian embryo. J Exp Med 210:2833–2842. https://doi.org/10.1084/jem.20130733
Gaspar J, Thai S, Voland C et al (2002) Opposing functions of the Ets factors NERF and ELF-1 during chicken blood vessel development. Arterioscler Thromb Vasc Biol 22:1106–1112
Gasparini G, Weidner N, Bevilacqua P et al (1994) Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol 12:454–466. https://doi.org/10.1200/JCO.1994.12.3.454
Géraud C, Koch P-S, Zierow J et al (2017) GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis. J Clin Invest 127:1099. https://doi.org/10.1172/JCI90086
Gerhardt H (2008) VEGF and endothelial guidance in angiogenic sprouting. Organogenesis 4:241–246
Ghatnekar A, Chrobak I, Reese C et al (2013) Endothelial GATA-6 deficiency promotes pulmonary arterial hypertension. Am J Pathol 182:2391–2406. https://doi.org/10.1016/j.ajpath.2013.02.039
Ghosh S, Hayden MS (2008) New regulators of NF-kappaB in inflammation. Nat Rev Immunol 8:837–848. https://doi.org/10.1038/nri2423
Giovannini M, Biegel JA, Serra M et al (1994) EWS-erg and EWS-Fli1 fusion transcripts in Ewing’s sarcoma and primitive neuroectodermal tumors with variant translocations. J Clin Invest 94:489–496. https://doi.org/10.1172/JCI117360
Grandori C, Cowley SM, James LP, Eisenman RN (2000) The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 16:653–699. https://doi.org/10.1146/annurev.cellbio.16.1.653
Greer EL, Brunet A (2005) FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24:7410–7425. https://doi.org/10.1038/sj.onc.1209086
Hamaguchi Y, Yamamoto Y, Iwanari H et al (1992) Biochemical and immunological characterization of the DNA binding protein (RBP-J kappa) to mouse J kappa recombination signal sequence. J Biochem 112:314–320
Hamik A, Lin Z, Kumar A et al (2007) Kruppel-like factor 4 regulates endothelial inflammation. J Biol Chem 282:13769–13779. https://doi.org/10.1074/jbc.M700078200
Hergenreider E, Heydt S, Tréguer K et al (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14:249–256. https://doi.org/10.1038/ncb2441
Ho J, Benchimol S (2003) Transcriptional repression mediated by the p53 tumour suppressor. Cell Death Differ 10:404–408. https://doi.org/10.1038/sj.cdd.4401191
Hollenhorst PC, Jones DA, Graves BJ (2004) Expression profiles frame the promoter specificity dilemma of the ETS family of transcription factors. Nucleic Acids Res 32:5693–5702. https://doi.org/10.1093/nar/gkh906
Hollenhorst PC, Shah AA, Hopkins C, Graves BJ (2007) Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family. Genes Dev 21:1882–1894. https://doi.org/10.1101/gad.1561707
Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53
Hoot KE, Oka M, Han G et al (2010) HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletion. J Clin Invest 120:3606–3616. https://doi.org/10.1172/JCI43304
Horowitz A, Simons M (2008) Branching morphogenesis. Circ Res 103:784–795. https://doi.org/10.1161/CIRCRESAHA.108.181818
Hosaka T, Biggs WH, Tieu D et al (2004) Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci USA 101:2975–2980. https://doi.org/10.1073/pnas.0400093101
Hosoya T, Maruyama A, Kang M-I et al (2005) Differential responses of the Nrf2-Keap1 system to laminar and oscillatory shear stresses in endothelial cells. J Biol Chem 280:27244–27250. https://doi.org/10.1074/jbc.M502551200
Hu C-J, Wang L-Y, Chodosh LA et al (2003) Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol 23:9361–9374
Ishii T, Itoh K, Takahashi S et al (2000) Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem 275:16023–16029
Ivan M, Kondo K, Yang H et al (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:464–468. https://doi.org/10.1126/science.1059817
Jaakkola P, Mole DR, Tian Y-M et al (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468–472. https://doi.org/10.1126/science.1059796
Johnson KD, Hsu AP, Ryu M-J et al (2012) Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity. J Clin Invest 122:3692–3704. https://doi.org/10.1172/JCI61623
Kaelin WG, Ratcliffe PJ (2008) Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30:393–402. https://doi.org/10.1016/j.molcel.2008.04.009
Kanki Y, Kohro T, Jiang S et al (2011) Epigenetically coordinated GATA2 binding is necessary for endothelium-specific endomucin expression. EMBO J 30:2582–2595. https://doi.org/10.1038/emboj.2011.173
Kim J, Gao P, Liu Y-C et al (2007) Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol 27:7381–7393. https://doi.org/10.1128/MCB.00440-07
Kobayashi M, Yamamoto M (2005) Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxid Redox Signal 7:385–394. https://doi.org/10.1089/ars.2005.7.385
Kottakis F, Polytarchou C, Foltopoulou P et al (2011) FGF-2 regulates cell proliferation, migration, and angiogenesis through an NDY1/KDM2B-miR-101-EZH2 pathway. Mol Cell 43:285–298. https://doi.org/10.1016/j.molcel.2011.06.020
Koutsourakis M, Langeveld A, Patient R et al (1999) The transcription factor GATA6 is essential for early extraembryonic development. Development 126:723–732
Kovall RA, Blacklow SC (2010) Mechanistic insights into notch receptor signaling from structural and biochemical studies. In: Current topics in developmental biology. Academic, San Diego, pp 31–71
Krebs LT, Shutter JR, Tanigaki K et al (2004) Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants. Genes Dev 18:2469–2473. https://doi.org/10.1101/gad.1239204
Kruse EA, Loughran SJ, Baldwin TM et al (2009) Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage. Proc Natl Acad Sci USA 106:13814–13819. https://doi.org/10.1073/pnas.0906556106
Kume T, Jiang H, Topczewska JM, Hogan BL (2001) The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis. Genes Dev 15:2470–2482. https://doi.org/10.1101/gad.907301
Kuo CT, Veselits ML, Barton KP et al (1997) The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis. Genes Dev 11:2996–3006
Laverriere AC, MacNeill C, Mueller C et al (1994) GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J Biol Chem 269:23177–23184
Lee ME, Temizer DH, Clifford JA, Quertermous T (1991) Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells. J Biol Chem 266:16188–16192
Lee JS, Yu Q, Shin JT et al (2006) Klf2 is an essential regulator of vascular hemodynamic forces in vivo. Dev Cell 11:845–857. https://doi.org/10.1016/j.devcel.2006.09.006
Lee J-H, Kim T-S, Yang T-H et al (2008) A crucial role of WW45 in developing epithelial tissues in the mouse. EMBO J 27:1231–1242. https://doi.org/10.1038/emboj.2008.63
Lim K-C, Hosoya T, Brandt W et al (2012) Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning. J Clin Invest 122:3705–3717. https://doi.org/10.1172/JCI61619
Linnemann AK, O’Geen H, Keles S et al (2011) Genetic framework for GATA factor function in vascular biology. Proc Natl Acad Sci USA 108:13641–13646. https://doi.org/10.1073/pnas.1108440108
Loughran SJ, Kruse EA, Hacking DF et al (2008) The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat Immunol 9:810–819. https://doi.org/10.1038/ni.1617
Lugus JJ, Chung YS, Mills JC et al (2007) GATA2 functions at multiple steps in hemangioblast development and differentiation. Development 134:393–405. https://doi.org/10.1242/dev.02731
Martens JHA (2011) Acute myeloid leukemia: a central role for the ETS factor ERG. Int J Biochem Cell Biol 43:1413–1416. https://doi.org/10.1016/j.biocel.2011.05.014
Mason JC (2016) Cytoprotective pathways in the vascular endothelium. Do they represent a viable therapeutic target? Vasc Pharmacol 86:41–52. https://doi.org/10.1016/j.vph.2016.08.002
Messaoudi S, He Y, Gutsol A et al (2015) Endothelial Gata5 transcription factor regulates blood pressure. Nat Commun 6:8835. https://doi.org/10.1038/ncomms9835
Mole DR, Blancher C, Copley RR et al (2009) Genome-wide association of hypoxia-inducible Factor (HIF)-1α and HIF-2α DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem 284:16767–16775. https://doi.org/10.1074/jbc.M901790200
Morin-Kensicki EM, Boone BN, Howell M et al (2006) Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65. Mol Cell Biol 26:77–87. https://doi.org/10.1128/MCB.26.1.77-87.2006
Morishita K, Johnson DE, Williams LT (1995) A novel promoter for vascular endothelial growth factor receptor (flt-1) that confers endothelial-specific gene expression. J Biol Chem 270:27948–27953. https://doi.org/10.1074/JBC.270.46.27948
Nabel GJ, Verma IM (1993) Proposed NF-kappa B/I kappa B family nomenclature. Genes Dev 7:2063
Nakagawa O, McFadden DG, Nakagawa M et al (2000) Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling. Proc Natl Acad Sci USA 97:13655–13660. https://doi.org/10.1073/pnas.250485597
Nemer G, Nemer M (2002) Cooperative interaction between GATA5 and NF-ATc regulates endothelial-endocardial differentiation of cardiogenic cells. Development 129:4045–4055
Nishida W, Nakamura M, Mori S et al (2002) A triad of serum response factor and the GATA and NK families governs the transcription of smooth and cardiac muscle genes. J Biol Chem 277:7308–7317. https://doi.org/10.1074/jbc.M111824200
Nishimori H, Shiratsuchi T, Urano T et al (1997) A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Oncogene 15:2145–2150
Niture SK, Khatri R, Jaiswal AK (2014) Regulation of Nrf2-an update. Free Radic Biol Med 66:36–44. https://doi.org/10.1016/j.freeradbiomed.2013.02.008
Obach M, Navarro-Sabaté A, Caro J et al (2004) 6-Phosphofructo-2-kinase (pfkfb3) gene promoter contains hypoxia-inducible factor-1 binding sites necessary for transactivation in response to hypoxia. J Biol Chem 279:53562–53570. https://doi.org/10.1074/jbc.M406096200
Oh S, Lee D, Kim T et al (2009) Crucial role for Mst1 and Mst2 kinases in early embryonic development of the mouse. Mol Cell Biol 29:6309–6320. https://doi.org/10.1128/MCB.00551-09
Orkin SH (1992) GATA-binding transcription factors in hematopoietic cells. Blood 80:575–581
Pal S, Datta K, Mukhopadhyay D (2001) Central role of p53 on regulation of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in mammary carcinoma. Cancer Res 61:6952–6957
Pandolfi PP, Roth ME, Karis A et al (1995) Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet 11:40–44. https://doi.org/10.1038/ng0995-40
Park C, Kim TM, Malik AB (2013) Transcriptional regulation of endothelial cell and vascular development. Circ Res 112:1380–1400. https://doi.org/10.1161/CIRCRESAHA.113.301078
Park J, Mills C, Matter K et al (2017) YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation. Invest Ophthalmol Vis Sci 57:OCT331–OCT340. https://doi.org/10.1172/JCI93825
Parmar KM (2005) Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J Clin Invest 116:49–58. https://doi.org/10.1172/JCI24787
Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8:49–62. https://doi.org/10.1038/nrm2083
Petrova TV, Karpanen T, Norrmén C et al (2004) Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med 10:974–981. https://doi.org/10.1038/nm1094
Pham VN, Lawson ND, Mugford JW et al (2007) Combinatorial function of ETS transcription factors in the developing vasculature. Dev Biol 303:772–783. https://doi.org/10.1016/j.ydbio.2006.10.030
Piccolo S, Dupont S, Cordenonsi M (2014) The biology of YAP/TAZ: hippo signaling and beyond. Physiol Rev 94:1287
Pikkarainen S, Tokola H, Kerkelä R, Ruskoaho H (2004) GATA transcription factors in the developing and adult heart. Cardiovasc Res 63:196–207. https://doi.org/10.1016/j.cardiores.2004.03.025
Randi AM, Sperone A, Dryden NH, Birdsey GM (2009) Regulation of angiogenesis by ETS transcription factors. Biochem Soc Trans 37(6):1248–53. https://doi.org/10.1042/BST0371248
Ravi R, Mookerjee B, Bhujwalla ZM et al (2000) Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 14:34–44
Ribatti D (2006) Genetic and epigenetic mechanisms in the early development of the vascular system. J Anat 208:139–152. https://doi.org/10.1111/j.1469-7580.2006.00522.x
Risau W (1995) Differentiation of endothelium. FASEB J 9:926–933
Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674. https://doi.org/10.1038/386671a0
Robert-Moreno A, Espinosa L, de la Pompa JL et al (2005) RBPjkappa-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells. Development 132:1117–1126. https://doi.org/10.1242/dev.01660
Robinson AS, Materna SC, Barnes RM et al (2014) An arterial-specific enhancer of the human endothelin converting enzyme 1 (ECE1) gene is synergistically activated by Sox17, FoxC2, and Etv2. Dev Biol 395:379–389. https://doi.org/10.1016/j.ydbio.2014.08.027
Schmidt A, Brixius K, Bloch W (2007) Endothelial precursor cell migration during vasculogenesis. Circ Res 101:125–136. https://doi.org/10.1161/CIRCRESAHA.107.148932
Seo S, Fujita H, Nakano A et al (2006) The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev Biol 294:458–470. https://doi.org/10.1016/j.ydbio.2006.03.035
Sharrocks AD, Brown AL, Ling Y, Yates PR (1997) The ETS-domain transcription factor family. Int J Biochem Cell Biol 29:1371–1387
Shaywitz AJ, Greenberg ME (1999) CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 68:821–861. https://doi.org/10.1146/annurev.biochem.68.1.821
Shivdasani RA, Orkin SH (1996) The transcriptional control of hematopoiesis. Blood 87:4025–4039
Singh MK, Li Y, Li S et al (2010) Gata4 and Gata5 cooperatively regulate cardiac myocyte proliferation in mice. J Biol Chem 285:1765–1772. https://doi.org/10.1074/jbc.M109.038539
Singh NK, Kotla S, Kumar R, Rao GN (2015) Cyclic AMP response element binding protein mediates pathological retinal neovascularization via modulating DLL4-NOTCH1 signaling. EBioMedicine 2:1767–1784. https://doi.org/10.1016/j.ebiom.2015.09.042
Skuli N, Liu L, Runge A et al (2009) Endothelial deletion of hypoxia-inducible factor-2 (HIF-2) alters vascular function and tumor angiogenesis. Blood 114:469–477. https://doi.org/10.1182/blood-2008-12-193581
Song H, Suehiro J, Kanki Y et al (2009) Critical role for GATA3 in mediating Tie2 expression and function in large vessel endothelial cells. J Biol Chem 284:29109–29124. https://doi.org/10.1074/jbc.M109.041145
Song R, Tian K, Wang W, Wang L (2015) P53 suppresses cell proliferation, metastasis, and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway. Int J Surg 20:80–87. https://doi.org/10.1016/j.ijsu.2015.04.050
Soudais C, Bielinska M, Heikinheimo M et al (1995) Targeted mutagenesis of the transcription factor GATA-4 gene in mouse embryonic stem cells disrupts visceral endoderm differentiation in vitro. Development 121:3877–3888
Subbaramaiah K, Altorki N, Chung WJ et al (1999) Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem 274:10911–10915
Suchting S, Freitas C, le Noble F et al (2007) The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc Natl Acad Sci USA 104:3225–3230. https://doi.org/10.1073/pnas.0611177104
Suehiro J, Hamakubo T, Kodama T et al (2010) Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3. Blood 115:2520–2532. https://doi.org/10.1182/blood-2009-07-233478
Sumanas S, Lin S (2006) Ets1-related protein is a key regulator of vasculogenesis in zebrafish. PLoS Biol 4:e10. https://doi.org/10.1371/journal.pbio.0040010
Suzuki E, Evans T, Lowry J et al (1996) The human GATA-6 gene: structure, chromosomal location, and regulation of expression by tissue-specific and mitogen-responsive signals. Genomics 38:283–290. https://doi.org/10.1006/geno.1996.0630
Takabe W, Warabi E, Noguchi N (2011) Anti-atherogenic effect of laminar shear stress via Nrf2 activation. Antioxid Redox Signal 15:1415–1426. https://doi.org/10.1089/ars.2010.3433
Takahashi Y, Bucana CD, Cleary KR, Ellis LM (1998) p53, vessel count, and vascular endothelial growth factor expression in human colon cancer. Int J Cancer 79:34–38
Tang N, Wang L, Esko J et al (2004) Loss of HIF-1alpha in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell 6:485–495. https://doi.org/10.1016/j.ccr.2004.09.026
Teodoro JG, Parker AE, Zhu X, Green MR (2006) p53-mediated inhibition of angiogenesis through up-regulation of a collagen prolyl hydroxylase. Science 313:968–971. https://doi.org/10.1126/science.1126391
Tomlins SA, Palanisamy N, Brenner JC et al (2013) Usefulness of a monoclonal ERG/FLI1 antibody for immunohistochemical discrimination of Ewing family tumors. Am J Clin Pathol 139:771–779. https://doi.org/10.1309/AJCPN4L1BMRQPEIT
Tsai FY, Orkin SH (1997) Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood 89:3636–3643
Tsai F-YY, Keller G, Kuo FC et al (1994) An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 371:221–226. https://doi.org/10.1038/371221a0
Ueba T, Nosaka T, Takahashi JA et al (1994) Transcriptional regulation of basic fibroblast growth factor gene by p53 in human glioblastoma and hepatocellular carcinoma cells. Proc Natl Acad Sci USA 91:9009–9013
Umetani M, Mataki C, Minegishi N et al (2001) Function of GATA transcription factors in induction of endothelial vascular cell adhesion molecule-1 by tumor necrosis factor-α. Arterioscler Thromb Vasc Biol 21:917–922. https://doi.org/10.1161/01.ATV.21.6.917
van Hinsbergh VWM, Koolwijk P (2008) Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead. Cardiovasc Res 78:203–212. https://doi.org/10.1093/cvr/cvm102
Verger A, Buisine E, Carrère S et al (2001) Identification of amino acid residues in the ETS transcription factor Erg that mediate Erg-Jun/Fos-DNA ternary complex formation. J Biol Chem 276:17181–17189. https://doi.org/10.1074/jbc.M010208200
Villarreal G, Zhang Y, Larman HB et al (2010) Defining the regulation of KLF4 expression and its downstream transcriptional targets in vascular endothelial cells. Biochem Biophys Res Commun 391:984
Vousden KH, Lu X (2002) Live or let die: the cell’s response to p53. Nat Rev Cancer 2:594–604. https://doi.org/10.1038/nrc864
Wada H, Hasegawa K, Morimoto T et al (2000) A p300 protein as a coactivator of GATA-6 in the transcription of the smooth muscle-myosin heavy chain gene. J Biol Chem 275:25330–25335. https://doi.org/10.1074/jbc.M000828200
Warabi E, Takabe W, Minami T et al (2007) Shear stress stabilizes NF-E2-related factor 2 and induces antioxidant genes in endothelial cells: role of reactive oxygen/nitrogen species. Free Radic Biol Med 42:260–269. https://doi.org/10.1016/j.freeradbiomed.2006.10.043
Wellen KE, Thompson CB (2012) A two-way street: reciprocal regulation of metabolism and signalling. Nat Rev Mol Cell Biol 13:270–276. https://doi.org/10.1038/nrm3305
Wen AY, Sakamoto KM, Miller LS (2010) The role of the transcription factor CREB in immune function. J Immunol 185:6413–6419. https://doi.org/10.4049/jimmunol.1001829
Wilhelm K, Happel K, Eelen G et al (2016) FOXO1 couples metabolic activity and growth state in the vascular endothelium. Nature 529:216–220. https://doi.org/10.1038/nature16498
Winnier GE, Kume T, Deng K et al (1999) Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles. Dev Biol 213:418–431. https://doi.org/10.1006/dbio.1999.9382
Yu E, Yu E, Meyer G, Brawer M (1997) The relation of p53 protein nuclear accumulation and angiogenesis in human prostatic carcinoma. Prostate Cancer Prostatic Dis 1:39–44. https://doi.org/10.1038/sj.pcan.4500205
Yu F-X, Zhao B, Guan K-L (2015) Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell 163:811–828. https://doi.org/10.1016/j.cell.2015.10.044
Zakkar M, Van der Heiden K, Luong LA et al (2009) Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state. Arterioscler Thromb Vasc Biol 29:1851–1857. https://doi.org/10.1161/ATVBAHA.109.193375
Zhou S, Hayward SD (2001) Nuclear localization of CBF1 is regulated by interactions with the SMRT corepressor complex. Mol Cell Biol 21:6222–6232
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Hofmann, M., Heineke, J. (2019). The Impact of Endothelial Transcription Factors in Sprouting Angiogenesis. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-33673-2_38
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