Hệ thống yếu tố tăng trưởng nội mạch (VEGF)/receptor VEGF và vai trò của nó trong các điều kiện sinh lý và bệnh lý

Leung, 1989, Vascular endothelial growth factor is a secreted angiogenic mitogen, Science, 246, 1306, 10.1126/science.2479986

Keck, 1989, Vascular permeability factor, an endothelial cell mitogen related to PDGF, Science, 246, 1309, 10.1126/science.2479987

Shibuya, 1990, Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family, Oncogene, 5, 519

Matthews, 1991, A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit, Proc. Natl. Acad. Sci. U.S.A., 88, 9026, 10.1073/pnas.88.20.9026

Terman, 1991, Identification of a new endothelial cell growth factor receptor tyrosine kinase, Oncogene, 6, 1677

Connolly, 1989, Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis, J. Clin. Invest., 84, 1470, 10.1172/JCI114322

Ferrara, 1989, Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells, Biochem. Biophys. Res. Commun., 161, 851, 10.1016/0006-291X(89)92678-8

Senger, 1983, Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid, Science, 219, 983, 10.1126/science.6823562

Muller, 1997, Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site, Proc. Natl. Acad. Sci. U.S.A., 94, 7192, 10.1073/pnas.94.14.7192

Houck, 1991, The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA, Mol. Endocrinol., 5, 1806, 10.1210/mend-5-12-1806

Tischer, 1991, The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing., J. Biol. Chem., 266, 11947, 10.1016/S0021-9258(18)99049-6

Vincenti, 1996, Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3, Circulation, 93, 1493, 10.1161/01.CIR.93.8.1493

Lange, 2003, VEGF162, a new heparin-binding vascular endothelial growth factor splice form that is expressed in transformed human cells, J. Biol. Chem., 278, 17164, 10.1074/jbc.M212224200

Bates, 2002, Regulation of vascular permeability by vascular endothelial growth factors, Vascul. Pharmacol., 39, 225, 10.1016/S1537-1891(03)00011-9

Woolard, 2004, VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression, Cancer Res., 64, 7822, 10.1158/0008-5472.CAN-04-0934

Ferrara, 1997, The biology of vascular endothelial growth factor, Endocr. Rev., 18, 4, 10.1210/edrv.18.1.0287

Melter, 2000, Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo, Blood, 96, 3801, 10.1182/blood.V96.12.3801

Freeman, 1995, Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: a potential role for T cells in angiogenesis, Cancer Res., 55, 4140

Plouet, 1997, Extracellular cleavage of the vascular endothelial growth factor 189-amino acid form by urokinase is required for its mitogenic effect, J. Biol. Chem., 272, 13390, 10.1074/jbc.272.20.13390

Soker, 1998, Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor, Cell, 92, 735, 10.1016/S0092-8674(00)81402-6

Gluzman-Poltorak, 2000, Neuropilin-2 and neuropilin-1 are receptors for the 165-amino acid form of vascular endothelial growth factor (VEGF) and of placenta growth factor-2, but only neuropilin-2 functions as a receptor for the 145-amino acid form of VEGF, J. Biol. Chem., 275, 18040, 10.1074/jbc.M909259199

Carmeliet, 1999, Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188, Nat. Med., 5, 495, 10.1038/8379

Ruhrberg, 2002, Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis, Genes Dev., 16, 2684, 10.1101/gad.242002

Stalmans, 2002, Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms, J. Clin. Invest., 109, 327, 10.1172/JCI0214362

Maes, 2004, Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival, J. Clin. Invest., 113, 188, 10.1172/JCI200419383

Ivan, 2001, HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing, Science, 292, 464, 10.1126/science.1059817

Jaakkola, 2001, Targeting of HIF-α to the von Hippel–Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation, Science, 292, 468, 10.1126/science.1059796

Lando, 2002, Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch, Science, 295, 858, 10.1126/science.1068592

Gerald, 2004, JunD reduces tumor angiogenesis by protecting cells from oxidative stress, Cell, 118, 781, 10.1016/j.cell.2004.08.025

Levy, 1998, Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR, J. Biol. Chem., 273, 6417, 10.1074/jbc.273.11.6417

Onesto, 2004, Poly(A)-binding protein-interacting protein 2, a strong regulator of vascular endothelial growth factor mRNA, J. Biol. Chem., 279, 34217, 10.1074/jbc.M400219200

Xie, 2004, Constitutive and inducible expression and regulation of vascular endothelial growth factor, Cytokine Growth Factor Rev., 15, 297, 10.1016/j.cytogfr.2004.04.003

Maglione, 1991, Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor, Proc. Natl. Acad. Sci. U.S.A., 88, 9267, 10.1073/pnas.88.20.9267

Persico, 1999, Structure, expression and receptor-binding properties of placental growth factor (PlGF), Curr. Top. Microbiol. Immunol., 237, 31

Park, 1994, Placenta growth factor Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR, J. Biol. Chem., 269, 25646, 10.1016/S0021-9258(18)47298-5

Sawano, 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., 7, 213

Maglione, 1993, Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14, Oncogene, 8, 925

Cao, 1997, Placenta growth factor: identification and characterization of a novel isoform generated by RNA alternative splicing, Biochem. Biophys. Res. Commun., 235, 493, 10.1006/bbrc.1997.6813

Yang, 2003, Evidence of a novel isoform of placenta growth factor (PlGF-4) expressed in human trophoblast and endothelial cells, J. Reprod. Immunol., 60, 53, 10.1016/S0165-0378(03)00082-2

Iyer, 2001, The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 A resolution, J. Biol. Chem., 276, 12153, 10.1074/jbc.M008055200

Christinger, 2004, The crystal structure of placental growth factor in complex with domain 2 of vascular endothelial growth factor receptor-1, J. Biol. Chem., 279, 10382, 10.1074/jbc.M313237200

Errico, 2004, Identification of placenta growth factor determinants for binding and activation of Flt-1 receptor, J. Biol. Chem., 279, 43929, 10.1074/jbc.M401418200

Carmeliet, 2001, Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions, Nat. Med., 7, 575, 10.1038/87904

Olofsson, 1999, Current biology of VEGF-B and VEGF-C, Curr. Opin. Biotechnol., 10, 528, 10.1016/S0958-1669(99)00024-5

Bellomo, 2000, Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia, Circ. Res., 86, E29, 10.1161/01.RES.86.2.e29

Aase, 2001, Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect, Circulation, 104, 358, 10.1161/01.CIR.104.3.358

Mould, 2003, Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis, Arthritis Rheum., 48, 2660, 10.1002/art.11232

Sun, 2004, Increased severity of cerebral ischemic injury in vascular endothelial growth factor-B-deficient mice, J. Cereb. Blood Flow Metab., 24, 1146, 10.1097/01.WCB.0000134477.38980.38

Lohela, 2003, Lymphangiogenic growth factors, receptors and therapies, Thromb. Haemostasis, 90, 167, 10.1160/TH03-04-0200

McColl, 2003, Plasmin activates the lymphangiogenic growth factors VEGF-C and VEGF-D, J. Exp. Med., 198, 863, 10.1084/jem.20030361

Jeltsch, 1997, Hyperplasia of lymphatic vessels in VEGF-C transgenic mice, Science, 276, 1423, 10.1126/science.276.5317.1423

Karkkainen, 2004, Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins, Nat. Immunol., 5, 74, 10.1038/ni1013

Stacker, 2001, VEGF-D promotes the metastatic spread of tumor cells via the lymphatics, Nat. Med., 7, 186, 10.1038/84635

Lyttle, 1994, Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus, J. Virol., 68, 84, 10.1128/jvi.68.1.84-92.1994

Wise, 1999, Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1, Proc. Natl. Acad. Sci. U.S.A., 96, 3071, 10.1073/pnas.96.6.3071

Ogawa, 1998, A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain, J. Biol. Chem., 273, 31273, 10.1074/jbc.273.47.31273

Wise, 2003, Viral vascular endothelial growth factors vary extensively in amino acid sequence, receptor-binding specificities, and the ability to induce vascular permeability yet are uniformly active mitogens, J. Biol. Chem., 278, 38004, 10.1074/jbc.M301194200

Meyer, 1999, A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases, EMBO J., 18, 363, 10.1093/emboj/18.2.363

Kiba, 2003, VEGFR-2-specific ligand VEGF-E induces non-edematous hyper-vascularization in mice, Biochem. Biophys. Res. Commun., 301, 371, 10.1016/S0006-291X(02)03033-4

Junqueira de Azevedo, 2001, Molecular cloning and expression of a functional snake venom vascular endothelium growth factor (VEGF) from the Bothrops insularis pit viper. A new member of the VEGF family of proteins, J. Biol. Chem., 276, 39836, 10.1074/jbc.M106531200

Takahashi, 2004, A novel snake venom vascular endothelial growth factor (VEGF) predominantly induces vascular permeability through preferential signaling via VEGF receptor-1, J. Biol. Chem., 279, 46304, 10.1074/jbc.M403687200

Komori, 1999, Vascular endothelial growth factor VEGF-like heparin-binding protein from the venom of Vipera aspis aspis (Aspic viper), Biochemistry, 38, 11796, 10.1021/bi990562z

Gasmi, 2002, Complete structure of an increasing capillary permeability protein (ICPP) purified from Vipera lebetina venom. ICPP is angiogenic via vascular endothelial growth factor receptor signalling, J. Biol. Chem., 277, 29992, 10.1074/jbc.M202202200

Yamazaki, 2003, Snake venom vascular endothelial growth factors (VEGFs) exhibit potent activity through their specific recognition of KDR (VEGF receptor 2), J. Biol. Chem., 278, 51985, 10.1074/jbc.C300454200

Sawano, 2001, Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans, Blood, 97, 785, 10.1182/blood.V97.3.785

Hattori, 2002, Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1+ stem cells from bone-marrow microenvironment, Nat. Med., 8, 841, 10.1038/nm740

Wiesmann, 1997, Crystal structure at 1.7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor, Cell, 91, 695, 10.1016/S0092-8674(00)80456-0

Kanno, 2000, Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial cells, Oncogene, 19, 2138, 10.1038/sj.onc.1203533

Kendall, 1996, Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR, Biochem. Biophys. Res. Commun., 226, 324, 10.1006/bbrc.1996.1355

Toi, 2002, Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer, Int. J. Cancer, 98, 14, 10.1002/ijc.10121

Scheufler, 2003, Implications of vascular endothelial growth factor, sFlt-1, and sTie-2 in plasma, serum and cerebrospinal fluid during cerebral ischemia in man, J. Cereb. Blood Flow Metab., 23, 99, 10.1097/01.WCB.0000037547.46809.83

Levine, 2004, Circulating angiogenic factors and the risk of preeclampsia, New Engl. J. Med., 350, 672, 10.1056/NEJMoa031884

Maynard, 2003, Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia, J. Clin. Invest., 111, 649, 10.1172/JCI17189

Fuh, 1998, Requirements for binding and signaling of the kinase domain receptor for vascular endothelial growth factor, J. Biol. Chem., 273, 11197, 10.1074/jbc.273.18.11197

Katoh, 1995, Expression of the vascular endothelial growth factor (VEGF) receptor gene, KDR, in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death caused by ionizing radiation, Cancer Res., 55, 5687

Takahashi, 2001, A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-γ and DNA synthesis in vascular endothelial cells, EMBO J., 20, 2768, 10.1093/emboj/20.11.2768

Wu, 2000, VRAP is an adaptor protein that binds KDR, a receptor for vascular endothelial cell growth factor, J. Biol. Chem., 275, 6059, 10.1074/jbc.275.9.6059

Warner, 2000, The Shc-related adaptor protein, Sck, forms a complex with the vascular-endothelial-growth-factor receptor KDR in transfected cells, Biochem. J., 347, 501, 10.1042/bj3470501

Holmqvist, 2004, The adaptor protein shb binds to tyrosine 1175 in vascular endothelial growth factor (VEGF) receptor-2 and regulates VEGF-dependent cellular migration, J. Biol. Chem., 279, 22267, 10.1074/jbc.M312729200

Nagy, 2002, Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis, J. Exp. Med., 196, 1497, 10.1084/jem.20021244

Hong, 2004, VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the α1β1 and α2β1 integrins, FASEB J., 18, 1111, 10.1096/fj.03-1179fje

Gerber, 1998, Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation, J. Biol. Chem., 273, 30336, 10.1074/jbc.273.46.30336

Fujio, 1999, Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner, J. Biol. Chem., 274, 16349, 10.1074/jbc.274.23.16349

Byzova, 2000, A mechanism for modulation of cellular responses to VEGF: activation of the integrins, Mol. Cell, 6, 851

Ebos, 2004, A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma, Mol. Cancer Res., 2, 315, 10.1158/1541-7786.315.2.6

Makinen, 2001, Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3, Nat. Med., 7, 199, 10.1038/84651

Veikkola, 2001, Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice, EMBO J., 20, 1223, 10.1093/emboj/20.6.1223

Makinen, 2001, Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3, EMBO J., 20, 4762, 10.1093/emboj/20.17.4762

Chen, 2004, Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity, Nat. Med., 10, 813, 10.1038/nm1078

Neufeld, 2002, The neuropilins: multifunctional semaphorin and VEGF receptors that modulate axon guidance and angiogenesis, Trends Cardiovasc. Med., 12, 13, 10.1016/S1050-1738(01)00140-2

Takahashi, 1999, Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors, Cell, 99, 59, 10.1016/S0092-8674(00)80062-8

Takahashi, 2001, Plexina1 autoinhibition by the plexin sema domain, Neuron, 29, 429, 10.1016/S0896-6273(01)00216-1

Whitaker, 2001, Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor complex that is responsible for the differential signaling potency of VEGF165 and VEGF121, J. Biol. Chem., 276, 25520, 10.1074/jbc.M102315200

Soker, 2002, VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding, J. Cell. Biochem., 85, 357, 10.1002/jcb.10140

Kitsukawa, 1995, Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs, Development, 121, 4309, 10.1242/dev.121.12.4309

Kawasaki, 1999, A requirement for neuropilin-1 in embryonic vessel formation, Development, 126, 4895, 10.1242/dev.126.21.4895

Yuan, 2002, Abnormal lymphatic vessel development in neuropilin 2 mutant mice, Development, 129, 4797, 10.1242/dev.129.20.4797

Carmeliet, 1996, Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele, Nature (London), 380, 435, 10.1038/380435a0

Ferrara, 1996, Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene, Nature (London), 380, 439, 10.1038/380439a0

Miquerol, 2000, Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression, Development, 127, 3941, 10.1242/dev.127.18.3941

Fong, 1995, Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium, Nature (London), 376, 66, 10.1038/376066a0

Shalaby, 1995, Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice, Nature (London), 376, 62, 10.1038/376062a0

Hiratsuka, 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, 9349, 10.1073/pnas.95.16.9349

Takahashi, 1999, VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells, Oncogene, 18, 2221, 10.1038/sj.onc.1202527

Sakurai, 2005, Essential role of Flk-1 (vascular endothelial growth factor receptor-2) tyrosine residue 1173 in vasculogenesis in mice, Proc. Natl. Acad. Sci. U.S.A., 102, 1076, 10.1073/pnas.0404984102

Lamalice, 2004, Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38, Oncogene, 23, 434, 10.1038/sj.onc.1207034

Vinals, 1999, p70 S6 kinase-mediated protein synthesis is a critical step for vascular endothelial cell proliferation, J. Biol. Chem., 274, 26776, 10.1074/jbc.274.38.26776

Yamazaki, 2004, Puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) binds and catalyzes PDK1, allowing VEGF-stimulated activation of S6K for endothelial cell proliferation and angiogenesis, Blood, 104, 2345, 10.1182/blood-2003-12-4260

Baldanzi, 2004, Activation of diacylglycerol kinase α is required for VEGF-induced angiogenic signaling in vitro, Oncogene, 23, 4828, 10.1038/sj.onc.1207633

Chai, 2004, Serum response factor is a critical requirement for VEGF signaling in endothelial cells and VEGF-induced angiogenesis, FASEB J., 18, 1264, 10.1096/fj.03-1232fje

Zhou, 2004, Vascular endothelial growth factor activation of sterol regulatory element binding protein: a potential role in angiogenesis, Circ. Res., 95, 471, 10.1161/01.RES.0000139956.42923.4A

Yamaoka-Tojo, 2004, IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species–dependent endothelial migration and proliferation, Circ. Res., 95, 276, 10.1161/01.RES.0000136522.58649.60

Watanabe, 2004, Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis, J. Clin. Invest., 114, 898, 10.1172/JCI200421152

Hesser, 2004, Down syndrome critical region protein 1 (DSCR1), a novel VEGF target gene that regulates expression of inflammatory markers on activated endothelial cells, Blood, 104, 149, 10.1182/blood-2004-01-0273

Minami, 2004, Vascular endothelial growth factor- and thrombin-induced termination factor, down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis, J. Biol. Chem., 279, 50537, 10.1074/jbc.M406454200

Luo, 1998, Significant expression of vascular endothelial growth factor/vascular permeability factor in mouse ascites tumors, Cancer Res., 58, 2652

Zebrowski, 1999, Vascular endothelial growth factor levels and induction of permeability in malignant pleural effusions, Clin. Cancer Res., 5, 3364

Kevil, 1998, Vascular permeability factor/vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial junctional proteins, J. Biol. Chem., 273, 15099, 10.1074/jbc.273.24.15099

Eliceiri, 1999, Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability, Mol. Cell, 4, 915, 10.1016/S1097-2765(00)80221-X

Weis, 2004, Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction, J. Clin. Invest., 113, 885, 10.1172/JCI200420702

Fukumura, 1997, Role of nitric oxide in tumor microcirculation. Blood flow, vascular permeability, and leukocyte-endothelial interactions, Am. J. Pathol., 150, 713

Fukumura, 2001, Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability, Proc. Natl. Acad. Sci. U.S.A., 98, 2604, 10.1073/pnas.041359198

Fulton, 1999, Regulation of endothelium-derived nitric oxide production by the protein kinase Akt, Nature (London), 399, 597, 10.1038/21218

Dimmeler, 1999, Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation, Nature (London), 399, 601, 10.1038/21224

Eriksson, 2003, Small GTP-binding protein Rac is an essential mediator of vascular endothelial growth factor-induced endothelial fenestrations and vascular permeability, Circulation, 107, 1532, 10.1161/01.CIR.0000055324.34758.32

Issbrucker, 2003, p38 MAP kinase–a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability, FASEB J., 17, 262, 10.1096/fj.02-0329fje

Fukumura, 1998, Tumor induction of VEGF promoter activity in stromal cells, Cell, 94, 715, 10.1016/S0092-8674(00)81731-6

Holmgren, 1995, Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression, Nat. Med., 1, 149, 10.1038/nm0295-149

Ferrara, 2004, Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer, Nat. Rev. Drug Discov., 3, 391, 10.1038/nrd1381

Hiratsuka, 2001, Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis, Cancer Res., 61, 1207

Autiero, 2003, Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1, Nat. Med., 9, 936, 10.1038/nm884

Yoshiji, 2004, Halting the interaction between vascular endothelial growth factor and its receptors attenuates liver carcinogenesis in mice, Hepatology, 39, 1517, 10.1002/hep.20218

Christofori, 1995, Vascular endothelial growth factor and its receptors, flt-1 and flk-1, are expressed in normal pancreatic islets and throughout islet cell tumorigenesis, Mol. Endocrinol., 9, 1760

Inoue, 2002, VEGF-A has a critical, nonredundant role in angiogenic switching and pancreatic β cell carcinogenesis, Cancer Cell, 1, 193, 10.1016/S1535-6108(02)00031-4

Bergers, 2000, Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis, Nat. Cell Biol., 2, 737, 10.1038/35036374

Weis, 2004, Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis, J. Cell Biol., 167, 223, 10.1083/jcb.200408130

Schmitt, 2004, Disruption of hepatocellular tight junctions by vascular endothelial growth factor (VEGF): a novel mechanism for tumor invasion, J. Hepatol., 41, 274, 10.1016/j.jhep.2004.04.035

Hiratsuka, 2002, MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis, Cancer Cell, 2, 289, 10.1016/S1535-6108(02)00153-8

Hurwitz, 2004, Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer, New Engl. J. Med., 350, 2335, 10.1056/NEJMoa032691

Melder, 1996, During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium, Nat. Med., 2, 992, 10.1038/nm0996-992

Kim, 2001, Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factor-κB activation in endothelial cells, J. Biol. Chem., 276, 7614, 10.1074/jbc.M009705200

Barleon, 1996, Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1, Blood, 87, 3336, 10.1182/blood.V87.8.3336.bloodjournal8783336

Detmar, 1998, Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice, J. Invest. Dermatol., 111, 1, 10.1046/j.1523-1747.1998.00262.x

Kunstfeld, 2004, Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia, Blood, 104, 1048, 10.1182/blood-2003-08-2964

Oura, 2003, A critical role of placental growth factor in the induction of inflammation and edema formation, Blood, 101, 560, 10.1182/blood-2002-05-1516

Matsumoto, 2002, Possible involvement of the vascular endothelial growth factor-Flt-1-focal adhesion kinase pathway in chemotaxis and the cell proliferation of osteoclast precursor cells in arthritic joints, J. Immunol., 168, 5824, 10.4049/jimmunol.168.11.5824

Luttun, 2002, Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1, Nat. Med., 8, 831, 10.1038/nm731

De Bandt, 2003, Blockade of vascular endothelial growth factor receptor I (VEGF-RI), but not VEGF-RII, suppresses joint destruction in the K/BxN model of rheumatoid arthritis, J. Immunol., 171, 4853, 10.4049/jimmunol.171.9.4853

Lee, 2001, Vascular endothelial growth factor in patients with acute asthma, J. Allergy Clin. Immunol., 107, 1106, 10.1067/mai.2001.115628

Hoshino, 2001, Gene expression of vascular endothelial growth factor and its receptors and angiogenesis in bronchial asthma, J. Allergy Clin. Immunol., 107, 1034, 10.1067/mai.2001.115626

Lee, 2004, Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung, Nat. Med., 10, 1095, 10.1038/nm1105

Reinders, 2003, Proinflammatory functions of vascular endothelial growth factor in alloimmunity, J. Clin. Invest., 112, 1655, 10.1172/JCI17712

Zhao, 2004, Essential role of vascular endothelial growth factor and Flt-1 signals in neointimal formation after periadventitial injury, Arterioscler., Thromb., Vasc. Biol., 24, 2284, 10.1161/01.ATV.0000147161.42956.80

Marti, 2000, Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia, Am. J. Pathol., 156, 965, 10.1016/S0002-9440(10)64964-4

van Bruggen, 1999, VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain, J. Clin. Invest., 104, 1613, 10.1172/JCI8218

Paul, 2001, Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke, Nat. Med., 7, 222, 10.1038/84675

Sun, 2003, VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia, J. Clin. Invest., 111, 1843, 10.1172/JCI200317977

Manoonkitiwongsa, 2004, Neuroprotection of ischemic brain by vascular endothelial growth factor is critically dependent on proper dosage and may be compromised by angiogenesis, J. Cereb. Blood Flow Metab., 24, 693, 10.1097/01.WCB.0000126236.54306.21

Campochiaro, 2003, Ocular neovascularization: a valuable model system, Oncogene, 22, 6537, 10.1038/sj.onc.1206773

Gragoudas, 2004, Pegaptanib for neovascular age-related macular degeneration, New Engl. J. Med., 351, 2805, 10.1056/NEJMoa042760

Oosthuyse, 2001, Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration, Nat. Genet., 28, 131, 10.1038/88842

Lambrechts, 2003, VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death, Nat. Genet., 34, 383, 10.1038/ng1211

Azzouz, 2004, VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model, Nature (London), 429, 413, 10.1038/nature02544

Storkebaum, 2005, Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS, Nat. Neurosci., 8, 85, 10.1038/nn1360

LeCouter, 2003, Angiogenesis-independent endothelial protection of liver: role of VEGFR-1, Science, 299, 890, 10.1126/science.1079562

Dixelius, 2003, Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites, J. Biol. Chem., 278, 40973, 10.1074/jbc.M304499200

Cao, 2004, VEGF links hippocampal activity with neurogenesis, learning and memory, Nat. Genet., 36, 827, 10.1038/ng1395