Vascular endothelial growth factor signaling in hypoxia and inflammation

Journal of Neuroimmune Pharmacology

Volumn 9, Issue 2, 2014, Pages 142-160

  Ramakrishnan, S ^a   Anand, Vidhu ^b   Roy, Sabita ^a,b  

^a UNIVERSITY OF MINNESOTA   (United States)

^b UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

HIF; Hypoxia; Inflammation; Receptor signaling; VEGF

Indexed keywords

AE 941; AXITINIB; BEVACIZUMAB; CEDIRANIB; CHEMOKINE; CYTOKINE; GROWTH FACTOR; HYPOXIA INDUCIBLE FACTOR; HYPOXIA INDUCIBLE FACTOR 1; HYPOXIA INDUCIBLE FACTOR 2ALPHA; HYPOXIA INDUCIBLE FACTOR 3ALPHA; MICRORNA; OXYGEN; PAZOPANIB; PEGAPTANIB; RANIBIZUMAB; SORAFENIB; SUNITINIB; TRANSCRIPTOME; VANDETANIB; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; VATALANIB; VASCULOTROPIN A;

ANGIOGENESIS; BLOOD VESSEL PERMEABILITY; DRUG TARGETING; EXTRACELLULAR MATRIX; FEMALE GENITAL SYSTEM; HEMATOLOGIC MALIGNANCY; HOMEOSTASIS; HUMAN; HYPOXIA; INFLAMMATION; INFLAMMATORY CELL; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; OXYGEN SENSING; PH; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN MODIFICATION; REVIEW; SIGNAL TRANSDUCTION; SOLID TUMOR; TRANSCRIPTION REGULATION; ANIMAL; ANOXIA; METABOLISM; PHYSIOLOGY;

ANIMALS; ANOXIA; HUMANS; INFLAMMATION; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84896543112     PISSN: 15571890     EISSN: 15571904     Source Type: Journal    
DOI: 10.1007/s11481-014-9531-7     Document Type: Review

References (181)

1. Alitalo K, Carmeliet P (2002) Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 1(3):219-227 (Pubitemid 41039145)
2. Ando H et al (2013) A hypoxia-inducible factor (HIF)-3alpha splicing variant, HIF-3alpha4 impairs angiogenesis in hypervascular malignant meningiomas with epigenetically silenced HIF-3alpha4. Biochem Biophys Res Commun 433(1):139-144
3. Andreoli CM, Miller JW (2007) Anti-vascular endothelial growth factor therapy for ocular neovascular disease. Curr Opin Ophthalmol 18(6):502-508 (Pubitemid 351339405)
4. Antoine M et al (2005) Upregulation of pleiotrophin expression in rat hepatic stellate cells by PDGF and hypoxia: implications for its role in experimental biliary liver fibrogenesis. Biochem Biophys Res Commun 337(4):1153-1164 (Pubitemid 41505246)
5. Arnaud C, Poulain L, Levy P, Dematteis M (2011) Inflammation contributes to the atherogenic role of intermittent hypoxia in apolipoprotein-E knock out mice. Atherosclerosis 219(2):425-431
6. Barreiro O et al (2002) Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol 157(7):1233-1245 (Pubitemid 34847793)
7. Battaglia F et al (2008) Hypoxia transcriptionally induces macrophage-inflammatory protein-3alpha/CCL-20 in primary human mononuclear phagocytes through nuclear factor (NF)-kappaB. J Leukoc Biol 83(3):648-662 (Pubitemid 351966875)
8. Bella J, Kolatkar PR, Marlor CW, Greve JM, Rossmann MG (1998) The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand. Proc Natl Acad Sci U S A 95(8):4140-4145 (Pubitemid 28207878)
9. Bellot G et al (2009) Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 29(10):2570-2581
10. Bosco MC et al (2004) Hypoxia selectively inhibits monocyte chemoattractant protein-1 production by macrophages. J Immunol 172(3):1681-1690 (Pubitemid 38116816)
11. Bosco MC et al (2006) 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 177(3):1941-1955 (Pubitemid 44092535)
12. Bosco MC et al (2008) Monocytes and dendritic cells in a hypoxic environment: Spotlights on chemotaxis and migration. Immunobiology 213(9-10):733-749
13. Braunwald E (2013) Cardiovascular science: opportunities for translating research into improved care. J Clin Invest 123(1):6-10
14. Carmeliet P et al (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573):435-439 (Pubitemid 26102719)
15. Carmeliet P et al (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7(5):575-583 (Pubitemid 32448325)
16. Carriere V et al (2007) IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A 104(1):282-287 (Pubitemid 46068023)
17. Carroll VA, Ashcroft M (2006) Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway. Cancer Res 66(12):6264-6270
18. Chakravorty SJ, Craig A (2005) The role of ICAM-1 in plasmodium falciparum cytoadherence. Eur J Cell Biol 84(1):15-27
19. Chan SY et al (2009) MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab 10(4):273-284
20. Chang JH et al (2012) Corneal neovascularization: an anti-VEGF therapy review. Surv Ophthalmol 57(5):415-429
21. Chen WY, Chang MS (2009) IL-20 is regulated by hypoxia-inducible factor and up-regulated after experimental ischemic stroke. J Immunol 182(8):5003-5012
22. Chen M, Geng JG (2006) P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arc Immunol Ther Exp 54(2):75-84 (Pubitemid 44257345)
23. Chen R et al (2012) The acetylase/deacetylase couple CREB-binding protein/Sirtuin 1 controls hypoxia-inducible factor 2 signaling. J Biol Chem 287(36):30800-30811
24. Chistiakov DA, Sobenin IA, Orekhov AN (2012) Strategies to deliver microRNAs as potential therapeutics in the treatment of cardiovascular pathology. Drug Deliv 19(8):392-405
25. Cicchillitti L et al (2012) Hypoxia-inducible factor 1-alpha induces miR-210 in normoxic differentiating myoblasts. J Biol Chem 287(53):44761-44771
26. Ciulla TA, Rosenfeld PJ (2009) Anti-vascular endothelial growth factor therapy for neovascular ocular diseases other than age-related macular degeneration. Curr Opin Ophthalmol 20(3):166-174
27. Cleator JH, Zhu WQ, Vaughan DE, Hamm HE (2006) Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP. Blood 107(7):2736-2744
28. Cohen T et al (1995) VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell-surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells. J Biol Chem 270(19):11322-11326
29. Colgan SP, Taylor CT (2010) Hypoxia: an alarm signal during intestinal inflammation. Nat Rev Gastroenterol Hepatol 7(5):281-287
30. Dhondt J et al (2011) Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons. FASEB J Off Publ Fed Am Soc Exp Biol 25(5):1461-1473
31. Dias S et al (2000) Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J Clin Invest 106(4):511-521 (Pubitemid 30666384)
32. Dioum EM et al (2009) Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1. Science 324(5932):1289-1293
33. Dumont DJ et al (1998) Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science 282(5390):946-949 (Pubitemid 28507528)
34. Egger M et al (2007) Hypoxia up-regulates the angiogenic cytokine secretoneurin via anHIF-1alpha- and basic FGF-dependent pathway in muscle cells. FASEB J 21(11):2906-2917 (Pubitemid 47372757)
35. Eltzschig HK, Carmeliet P (2011) Hypoxia and inflammation. N Engl J Med 364(7):656-665
36. Ema M 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 U S A 94(9):4273-4278
37. Falanga Vet al (1991) Hypoxia upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts. J Invest Dermatol 97(4):634-637
38. Favaro E et al (2010) MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PloS ONE 5(4):e10345
39. Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25(4):581-611
40. Ferrara N (2010) Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action. Mol Biol Cell 21(5):687-690
41. Ferrara N et al (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573):439-442 (Pubitemid 26102720)
42. Florczyk U et al (2011) Opposite effects of HIF-1alpha and HIF-2alpha on the regulation of IL-8 expression in endothelial cells. Free Radic Biol Med 51(10):1882-1892
43. Fong GH, Rossant J, Gertsenstein M, Breitman ML (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376(6535):66-70
44. Frangogiannis NG, Smith CW, Entman ML (2002) The inflammatory response in myocardial infarction. Cardiovasc Res 53(1):31-47 (Pubitemid 34020764)
45. Fu H, Luo F, Yang L, Wu W, Liu X (2010) Hypoxia stimulates the expression of macrophage migration inhibitory factor in human vascular smooth muscle cells via HIF-1alpha dependent pathway. BMC Cell Biol 11:66
46. Fukumura D et al (1998) Tumor induction of VEGF promoter activity in stromal cells. Cell 94(6):715-725 (Pubitemid 28436004)
47. Gameiro PA et al (2013) In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab 17(3):372-385
48. Ganat Y, Soni S, Chacon M, Schwartz ML, Vaccarino FM (2002) Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone. Neuroscience 112(4):977-991 (Pubitemid 34667060)
49. Gerber HP, Ferrara N (2003) The role of VEGF in normal and neoplastic hematopoiesis. J Mol Med (Berl Germany) 81(1):20-31
50. Gerber HP, Kowalski J, Sherman D, Eberhard DA, Ferrara N (2000) Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Res 60(22):6253-6258
51. Ghezzi P et al (1991) Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells. Cytokine 3(3):189-194
52. Ghosh G et al (2010) Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-alpha isoforms and promotes angiogenesis. J Clin Invest 120(11):4141-4154
53. Gonsalves CS, Kalra VK (2010) Hypoxia-mediated expression of 5-lipoxygenase-activating protein involves HIF-1alpha and NF-kappaB and microRNAs 135a and 199a-5p. J Immunol 184(7):3878-3888
54. Greenberg DA, Jin K (2013) Vascular endothelial growth factors (VEGFs) and stroke. Cell Mol Life Sci 70(10):1753-1761
55. Gupta R, Tongers J, Losordo DW (2009) Human studies of angiogenic gene therapy. Circ Res 105(8):724-736
56. Hagberg CE et al (2010) Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature 464(7290):917-921
57. Hagberg CE et al (2012) Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. Nature 490(7420):426-430
58. Hagberg C, Mehlem A, Falkevall A, Muhl L, Eriksson U (2013) Endothelial fatty acid transport: role of vascular endothelial growth factor B. Physiology 28(2):125-134
59. Hagerling R et al (2013) A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy. EMBO J 32(5):629-644
60. Haiko P et al (2008) Deletion of vascular endothelial growth factor C (VEGF-C) and VEGF-D is not equivalent to VEGF receptor 3 deletion in mouse embryos. Mol Cell Biol 28(15):4843-4850
61. Hara S et al (2006) Hypoxia enhances c-Met/HGF receptor expression and signaling by activating HIF-1alpha in human salivary gland cancer cells. Oral Oncol 42(6):593-598 (Pubitemid 43947665)
62. Hedman M et al (2003) Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation 107(21):2677-2683 (Pubitemid 36667240)
63. Hedtjarn M et al (2002) Interleukin-18 involvement in hypoxic-ischemic brain injury. J Neurosci 22(14):5910-5919 (Pubitemid 35387635)
64. Heiska L et al (1998) Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol4, 5-bisphosphate. J Biol Chem 273(34):21893-21900 (Pubitemid 28405367)
65. Herz J et al (2012) Intracerebroventricularly delivered VEGF promotes contralesional corticorubral plasticity after focal cerebral ischemia via mechanisms involving anti-inflammatory actions. Neurobiol Dis 45(3):1077-1085
66. Hinkel R et al (2013) Inhibition of MicroRNA-92a protects against ischemia/reperfusion injury in a large-animal model. Circulation 128(10):1066-1075
67. Hirani N et al (2001) The regulation of interleukin-8 by hypoxia in human macrophages-a potential role in the pathogenesis of the acute respiratory distress syndrome (ARDS). Mol Med 7(10):685-697 (Pubitemid 33070983)
68. Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M (1998) Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci U S A 95(16):9349-9354 (Pubitemid 28506234)
69. Hitchon C et al (2002) Hypoxia-induced production of stromal cell-derived factor 1 (CXCL12) and vascular endothelial growth factor by synovial fibroblasts. Arthritis Rheum 46(10):2587-2597 (Pubitemid 36118921)
70. Hogan BM et al (2009) Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat Genet 41(4):396-398
71. Hong KH, Ryu J, Han KH (2005) Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A. Blood 105(4):1405-1407 (Pubitemid 40223654)
72. Horie N et al (2011) Transplanted stem cell-secreted VEGF effects post-stroke recovery, inflammation, and vascular repair. Stem Cells. doi: 10.1002/stem.584
73. Hu F et al (2013) Hypoxia-inducible factor-1alpha and interleukin 33 form a regulatory circuit to perpetuate the inflammation in rheumatoid arthritis. PloS ONE 8(8):e72650
74. Huang RB, Eniola-Adefeso O (2012) Shear stress modulation of IL-1beta-induced E-selectin expression in human endothelial cells. PloS ONE 7(2):e31874
75. Hubbi ME et al (2013a) Chaperone-mediated autophagy targets hypoxia-inducible factor-1alpha (HIF-1alpha) for lysosomal degradation. J Biol Chem 288(15):10703-10714
76. Hubbi ME, Hu H, Kshitiz GDM, Semenza GL (2013b) Sirtuin-7 inhibits the activity of hypoxia-inducible factors. J Biol Chem 288(29): 20768-20775
77. Hull ML et al (2003) Antiangiogenic agents are effective inhibitors of endometriosis. J Clin Endocrinol Metab 88(6):2889-2899 (Pubitemid 36733546)
78. Hullinger TG et al (2012) Inhibition of miR-15 protects against cardiac ischemic injury. Circ Res 110(1):71-81
79. Iadecola C, Alexander M (2001) Cerebral ischemia and inflammation. Curr Opin Neurol 14(1):89-94 (Pubitemid 32116263)
80. Iyer NV et al (1998) Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 12(2):149-162
81. Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7(9):987-989
82. Janssen BJ et al (2012) Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex. Nat Struct Mol Biol 19(12):1293-1299
83. Jeltsch M, Leppanen VM, Saharinen P, Alitalo K (2013) Receptor tyrosine kinase-mediated angiogenesis. Cold Spring Harb Perspect Biol 5(9). doi:10.1101/cshperspect.a009183
84. Jeong HJ et al (2005) Hypoxia-induced IL-6 production is associated with activation of MAP kinase, HIF-1, and NF-kappaB on HEI-OC1 cells. Hear Res 207(1-2):59-67
85. Jung YJ, Isaacs JS, Lee S, Trepel J, Neckers L (2003) IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB J Off Publ Fed Am Soc Exp Biol 17(14):2115-2117
86. Kaipainen A et al (1995) Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci U S A 92(8):3566-3570
87. Karakurum M et al (1994) Hypoxic induction of interleukin-8 gene expression in human endothelial cells. J Clin Invest 93(4):1564-1570 (Pubitemid 24116393)
88. Karkkainen MJ et al (2004) Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 5(1):74-80 (Pubitemid 38081471)
89. Kastrup J et al (2005) Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study: the Euroinject One trial. J Am Coll Cardiol 45(7):982-988 (Pubitemid 40432426)
90. Kelly TJ, Souza AL, Clish CB, Puigserver P (2011) A hypoxia-induced positive feedback loop promotes hypoxia-inducible factor 1alpha stability through miR-210 suppression of glycerol-3-phosphate dehydrogenase 1-like. Mol Cell Biol 31(13):2696-2706
91. Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2(10):727-739 (Pubitemid 37328908)
92. Kim J et al (2008) Hypoxia-induced IL-18 increases hypoxia-inducible factor-1alpha expression through a Rac1-dependent NF-kappaB pathway. Mol Biol Cell 19(2):433-444 (Pubitemid 351272133)
93. Kim JY, Kim N, Zheng Z, Lee JE, Yenari MA (2013) The 70 kDa heat shock protein protects against experimental traumatic brain injury. Neurobiol Dis 58:289-295
94. Kiss J et al (2012) Loss of the oxygen sensor PHD3 enhances the innate immune response to abdominal sepsis. J Immunol 189(4):1955-1965
95. Klement G et al (2000) Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 105(8):R15-R24 (Pubitemid 30217701)
96. Kotch LE, Iyer NV, Laughner E, Semenza GL (1999) Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency butwithmesenchymal cell death.Dev Biol 209(2):254-267 (Pubitemid 29230878)
97. Kulshreshtha R, Davuluri RV, Calin GA, Ivan M (2008) A microRNA component of the hypoxic response. Cell Death Differ 15(4):667-671 (Pubitemid 351405070)
98. Kurihara T, Westenskow PD, Bravo S, Aguilar E, Friedlander M (2012) Targeted deletion of Vegfa in adult mice induces vision loss. J Clin Invest 122(11):4213-4217
99. Kurokawa M et al (2013) Interleukin-33-activated dendritic cells induce the production of thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Arch Allergy Immunol 161(Suppl 2):52-57
100. Kusumanto YH et al (2006) Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial. Hum Gene Ther 17(6):683-691 (Pubitemid 43970708)
101. Lee CG et al (2000) Anti-Vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res 60(19):5565-5570
102. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935):1306-1309 (Pubitemid 20066716)
103. Lim JH et al (2010) Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha.Mol Cell 38(6):864-878
104. Loscalzo J (2010) The cellular response to hypoxia: tuning the system with microRNAs. J Clin Invest 120(11):3815-3817
105. Makinen K et al (2002) Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study. Mol Ther J Am Soc Gene Ther 6(1):127-133 (Pubitemid 36124280)
106. Makino Y et al (2007) Transcriptional up-regulation of inhibitory PAS domain protein gene expression by hypoxia-inducible factor 1 (HIF-1): a negative feedback regulatory circuit in HIF-1-mediated signaling in hypoxic cells. J Biol Chem 282(19):14073-14082 (Pubitemid 47100468)
107. Marchant DJ et al (2012) Inflammation in myocardial diseases. Circ Res 110(1):126-144
108. Marsch E, Sluimer JC, Daemen MJ (2013) Hypoxia in atherosclerosis and inflammation. Curr Opin Lipidol 24(5):393-400
109. Marumo T, Schini-Kerth VB, Busse R (1999) Vascular endothelial growth factor activates nuclear factor-kappaB and induces monocyte chemoattractant protein-1 in bovine retinal endothelial cells. Diabetes 48(5):1131-1137 (Pubitemid 29226362)
110. Maynard SE et al (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111(5):649-658
111. Maynard MA et al (2005) Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma. FASEB J Off Publ Fed Am Soc Exp Biol 19(11):1396-1406 (Pubitemid 41278998)
112. McCormick RI et al (2013) miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis. Br J Cancer 108(5):1133-1142
113. McEver RP, Beckstead JH, Moore KL, Marshall-Carlson L, Bainton DF (1989)GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest 84(1):92-99 (Pubitemid 19170099)
114. McLaren J et al (1996) Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest 98(2):482-489 (Pubitemid 26255749)
115. Metinko AP, Kunkel SL, Standiford TJ, Strieter RM (1992) Anoxia-hyperoxia induces monocyte-derived interleukin-8. J Clin Invest 90(3):791-798
116. Miller JW, Le Couter J, Strauss EC, Ferrara N (2013) Vascular endothelial growth factor a in intraocular vascular disease. Ophthalmology 120(1):106-114
117. Moussion C, Ortega N, Girard JP (2008) The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PloS ONE 3(10):e3331
118. Murakami M et al (2006) Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocytes/macrophages. Blood 108(6):1849-1856 (Pubitemid 44394993)
119. Murdoch C, Muthana M, Lewis CE (2005) Hypoxia regulates macrophage functions in inflammation. J Immunol 175(10):6257-6263 (Pubitemid 41598863)
120. Nimrichter L et al (2008) E-selectin receptors on human leukocytes. Blood 112(9):3744-3752
121. Noels H, Weber C (2011) Catching up with important players in atherosclerosis: type I interferons and neutrophils. Curr Opin Lipidol 22(2):144-145
122. Oosthuyse B et al (2001) Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet 28(2):131-138 (Pubitemid 32538057)
123. Peitsidis P, Agrawal R (2010) Role of vascular endothelial growth factor in women with PCO and PCOS: a systematic review. Reprod BioMed Online 20(4):444-452
124. Pellet-Many C, Frankel P, Jia H, Zachary I (2008) Neuropilins: structure, function and role in disease. Biochem J 411(2):211-226 (Pubitemid 351580173)
125. Peng H et al (2012) MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen metabolism. FASEB J 26(8):3140-3147
126. Pritchard-Jones RO et al (2007) Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma. Br J Cancer 97(2):223-230 (Pubitemid 47057469)
127. Pulkkinen K, Malm T, Turunen M, Koistinaho J, Yla-Herttuala S (2008) Hypoxia induces microRNA miR-210 in vitro and in vivo ephrin-A3 and neuronal pentraxin 1 are potentially regulated by miR-210. FEBS Lett 582(16):2397-2401
128. Rajagopalan S et al (2003) Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication. Circulation 108(16):1933-1938 (Pubitemid 37296537)
129. Ramakrishnan S (2011) Hydrogel-siRNA for cancer therapy. Cancer Biol Ther 11(9):849-851
130. Rane S et al (2009) Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ Res 104(7):879-886
131. Ricciardi A et al (2008) Transcriptome of hypoxic immature dendritic cells: modulation of chemokine/receptor expression. Mol Cancer Res 6(2):175-185 (Pubitemid 351342405)
132. Ripa RS et al (2006) Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte-colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease. Eur Heart J 27(15):1785-1792 (Pubitemid 44297382)
133. Rius J et al (2008) NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 453(7196):807-811 (Pubitemid 351793778)
134. Sakurai Y, Ohgimoto K, Kataoka Y, Yoshida N, Shibuya M (2005) Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc Natl Acad Sci U S A 102(4):1076-1081 (Pubitemid 40170728)
135. Sawano A, Takahashi T, Yamaguchi S, Aonuma M, Shibuya M (1996) Flt-1 but not KDR/Flk-1 tyrosine kinase is a receptor for placenta growth factor, which is related to vascular endothelial growth factor. Cell Growth Differ Mol Biol J Am Assoc Cancer Res 7(2):213-221 (Pubitemid 26049830)
136. Sawano A, Takahashi T, Yamaguchi S, Shibuya M (1997) The phosphorylated 1169-tyrosine containing region of flt-1 kinase (VEGFR-1) is a major binding site for PLCgamma. Biochem Biophys Res Commun 238(2):487-491 (Pubitemid 27464413)
137. Scannell G et al (1993) Hypoxia induces a humanmacrophage cell line to release tumor necrosis factor-alpha and its soluble receptors in vitro. J Surg Res 54(4):281-285 (Pubitemid 23235763)
138. Semenza GL (2013) HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 123(9):3664-3671
139. Semenza GL, Wang GL (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 12(12):5447-5454
140. Senger DR et al (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219(4587):983-985
141. Shibuya M (2011) Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer 2(12):1097-1105
142. Shin DH et al (2009) Inhibitor of nuclear factor-kappaB alpha derepresses hypoxia-inducible factor-1 during moderate hypoxia by sequestering factor inhibiting hypoxia-inducible factor from hypoxiainducible factor 1alpha. FEBS J 276(13):3470-3480
143. Simon MP, Tournaire R, Pouyssegur J (2008) The angiopoietin-2 gene of endothelial cells is up-regulated in hypoxia by a HIF binding site located in its first intron and by the central factors GATA-2 and Ets-1. J Cell Physiol 217(3):809-818
144. Simons D et al (2011) Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor and role in endothelial progenitor cell recruitment. J Cell Mol Med 15(3):668-678
145. Skuli N et al (2012) Endothelial HIF-2alpha regulates murine pathological angiogenesis and revascularization processes. J Clin Invest 122(4):1427-1443
146. Smith DF, Galkina E, Ley K, Huo Y (2005) GRO family chemokines are specialized for monocyte arrest from flow. Am J Physiol Heart Circ Physiol 289(5):H1976-H1984 (Pubitemid 41507347)
147. Smolich BD et al (2001) The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood 97(5):1413-1421 (Pubitemid 32183767)
148. Somers WS, Tang J, Shaw GD, Camphausen RT (2000) Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1. Cell 103(3):467-479
149. Son J et al (2013) Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496(7443):101-105
150. Sowter HM, Raval RR, Moore JW, Ratcliffe PJ, Harris AL (2003) Predominant role of hypoxia-inducible transcription factor (Hif)- 1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia. Cancer Res 63(19):6130-6134 (Pubitemid 37255150)
151. Sun Y et al (2003) VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 111(12):1843-1851 (Pubitemid 38057729)
152. Taguchi A et al (2008) Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster. Cancer Res 68(14):5540-5545
153. Takahashi M (2013) Role of innate immune system in inflammation and cardiac remodeling after myocardial infarction. Curr Vasc Pharmacol (in press) Takahashi T, Ueno H, Shibuya M (1999) VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene 18(13):2221-2230
154. Takahashi T, Yamaguchi S, Chida K, Shibuya M (2001) A single auto-phosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNAsynthesis in vascular endothelial cells. EMBO J 20(11):2768-2778 (Pubitemid 32938560)
155. Takyar S et al (2013) VEGF controls lung Th2 inflammation via the miR-1-Mpl (myeloproliferative leukemia virus oncogene)-P-selectin axis. J Exp Med 210(10):1993-2010
156. Tanaka H et al (2013) MicroRNA-183 upregulates HIF-1alpha by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells. J Neurooncol 111(3):273-283
157. ten Freyhaus H et al (2011) Hypoxia enhances platelet-derived growth factor signaling in the pulmonary vasculature by down-regulation of protein tyrosine phosphatases. Am J Respir Crit Care Med 183(8):1092-1102
158. Tewari R, Choudhury SR, Ghosh S, Mehta VS, Sen E (2012) Involvement of TNFalpha-induced TLR4-NF-kappaB and TLR4-HIF-1alpha feed-forward loops in the regulation of inflammatory responses in glioma. J Mol Med 90(1):67-80
159. Tian H, McKnight SL, Russell DW (1997) Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev 11(1):72-82 (Pubitemid 27043825)
160. Tian H, Hammer RE, Matsumoto AM, Russell DW, McKnight SL (1998) The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev 12(21):3320-3324 (Pubitemid 28520979)
161. Torii S et al (2011) Pro-apoptotic activity of inhibitory PAS domain protein (IPAS), a negative regulator of HIF-1, through binding to pro-survival Bcl-2 family proteins. Cell Death Differ 18(11):1711-1725
162. Trayhurn P (2013) Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev 93(1):1-21
163. Tuttolomondo A et al (2012) Inflammation in ischemic stroke subtypes. Curr Pharm Des 18(28):4289-4310 van den Boorn JG, Dassler J, Coch C, Schlee M, Hartmann G (2013) Exosomes as nucleic acid nanocarriers. Adv Drug Deliv Rev 65(3):331-335
164. Wahamaa H et al (2011) High mobility group box protein 1 in complex with lipopolysaccharide or IL-1 promotes an increased inflammatory phenotype in synovial fibroblasts. Arthritis Res Ther 13(4):R136
165. Wang Y et al (2009) Regulation of endocytosis via the oxygen-sensing pathway. Nat Med 15(3):319-324
166. Wang C et al (2011a) Underexpressed microRNA-199b-5p targets hypoxia-inducible factor-1alpha in hepatocellular carcinoma and predicts prognosis of hepatocellular carcinoma patients. J Gastroenterol Hepatol 26(11):1630-1637
167. Wang F et al (2011b) RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3K/Akt pathway. J Biol Chem 286(11):9097-9106
168. Wang Yet al (2012) Hypoxia promotes ligand-independent EGF receptor signaling via hypoxia-inducible factor-mediated upregulation of caveolin-1. Proc Natl Acad Sci U S A 109(13):4892-4897
169. Weber C, Noels H (2011) Atherosclerosis: current pathogenesis and therapeutic options. Nat Med 17(11):1410-1422
170. Wei Y, Schober A, Weber C (2013) Pathogenic arterial remodeling: the good and bad of microRNAs. Am J Physiol Heart Circ Physiol 304(8):H1050-H1059
171. White JR et al (2004) Genetic amplification of the transcriptional response to hypoxia as a novel means of identifying regulators of angiogenesis. Genomics 83(1):1-8 (Pubitemid 37518254)
172. Winning S, Splettstoesser F, Fandrey J, Frede S (2010) Acute hypoxia induces HIF-independent monocyte adhesion to endothelial cells through increased intercellular adhesion molecule-1 expression: the role of hypoxic inhibition of prolyl hydroxylase activity for the induction of NF-kappa B. J Immunol 185(3):1786-1793
173. Woltmann G, McNulty CA, Dewson G, Symon FA, Wardlaw AJ (2000) Interleukin-13 induces PSGL-1/P-selectin-dependent adhesion of eosinophils, but not neutrophils, to human umbilical vein endothelial cells under flow. Blood 95(10):3146-3152 (Pubitemid 30321166)
174. Yang L et al (2005) ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flow. Blood 106(2):584-592 (Pubitemid 40981255)
175. Yasuda K et al (2012) Contribution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice. Proc Natl Acad Sci U S A 109(9):3451-3456
176. Zampetaki A, Dudek K, Mayr M (2013) Oxidative stress in atherosclerosis: the role of microRNAs in arterial remodeling. Free Radic Biol Med 64:69-77
177. Zechariah A et al (2013a) Vascular endothelial growth factor promotes pericyte coverage of brain capillaries, improves cerebral blood flow during subsequent focal cerebral ischemia, and preserves the metabolic penumbra. Stroke J Cereb Circ 44(6):1690-1697
178. Zechariah A et al (2013b) Hyperlipidemia attenuates vascular endothelial growth factor-induced angiogenesis, impairs cerebral blood flow, and disturbs stroke recovery via decreased pericyte coverage of brain endothelial cells. Arterioscler Thromb Vasc Biol 33(7):1561-1567
179. Zhang H et al (2008) Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 283(16):10892-10903
180. Zheng Z, Yenari MA (2004) Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurol Res 26(8):884-892 (Pubitemid 39628566)
181. Zou X et al (2005) PSGL-1 derived from human neutrophils is a high-efficiency ligand for endothelium-expressed E-selectin under flow. Am J Physiol Cell Physiol 289(2):C415-C424 (Pubitemid 41008888)