Skip to main content
SpringerLink
Log in

Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease

  • Review
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival. The family of VEGF isoforms regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is implicated in major chronic disease states including atherosclerosis, diabetes, and cancer. More recent studies implicate a strong link between response to VEGF and regulation of vascular metabolism. Understanding how this family of multitasking cytokines regulates cell and animal function has implications for treating many different diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Al-Kateb H, Mirea L, Xie X et al (2007) Multiple variants in vascular endothelial growth factor (VEGFA) are risk factors for time to severe retinopathy in type 1 diabetes: the dcct/edic genetics study. Diabetes 56:2161–2168

    Article  CAS  PubMed  Google Scholar 

  • Avraham-Davidi I, Ely Y, Pham VN et al (2012) ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1. Nat Med 18:967–973

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Awata T, Inoue K, Kurihara S et al (2002) A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 51:1635–1639

    Article  CAS  PubMed  Google Scholar 

  • Buraczynska M, Ksiazek P, Baranowicz-Gaszczyk I et al (2007) Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients. Nephrol Dial Transplant 22:827–832

    Article  CAS  PubMed  Google Scholar 

  • Cai J, Ahmad S, Jiang WG et al (2003) Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells. Diabetes 52:2959–2968

    Article  CAS  PubMed  Google Scholar 

  • Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Carmeliet P, Ferreira V, Breier G et al (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435–439

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P, Moons L, Luttun A et al (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7:575–583

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P, De Smet F, Loges S et al (2009) Branching morphogenesis and antiangiogenesis candidates: tip cells lead the way. Nat Rev Clin Oncol 6:315–326

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P, Wong BW, De Bock K (2012) Treating diabetes by blocking a vascular growth factor. Cell Metab 16:553–555

    Article  CAS  PubMed  Google Scholar 

  • Chiarelli F, Gaspari S, Marcovecchio ML (2009) Role of growth factors in diabetic kidney disease. Horm Metab Res 41:585–593

    Article  CAS  PubMed  Google Scholar 

  • Churchill AJ, Carter JG, Ramsden C et al (2008) VEGF polymorphisms are associated with severity of diabetic retinopathy. Invest Ophthalmol Vis Sci 49:3611–3616

    Article  PubMed  Google Scholar 

  • Coultas L, Chawengsaksophak K, Rossant J (2005) Endothelial cells and VEGF in vascular development. Nature 438:937–945

    Article  CAS  PubMed  Google Scholar 

  • Cunningham SA, Arrate MP, Brock TA et al (1997) Interactions of Flt-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites. Biochem Biophys Res Commun 240:635–639

    Article  CAS  PubMed  Google Scholar 

  • Dagher Z, Ruderman N, Tornheim K et al (2001) Acute regulation of fatty acid oxidation and AMP-activated protein kinase in human umbilical vein endothelial cells. Circ Res 88:1276–1282

  • De Bock K, Georgiadou M, Carmeliet P (2013a) Role of endothelial cell metabolism in vessel sprouting. Cell Metab 18:634–647

    Article  PubMed  Google Scholar 

  • De Bock K, Georgiadou M, Schoors S et al (2013b) Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154:651–663

    Article  PubMed  Google Scholar 

  • De Saedeleer CJ, Copetti T, Porporato PE et al (2012) Lactate activates HIF-1 in oxidative but not in Warburg-phenotype human tumor cells. PLoS One 7:e46571

    Article  PubMed Central  PubMed  Google Scholar 

  • Devries C, Escobedo JA, Ueno H et al (1992) The Fms-like tyrosine kinase, a receptor for vascular endothelial growth-factor. Science 255:989–991

    Article  CAS  Google Scholar 

  • Eelen G, Cruys B, Welti J et al (2013) Control of vessel sprouting by genetic and metabolic determinants. Trends Endocrinol Metab 24:589–596

    Article  CAS  PubMed  Google Scholar 

  • Elmasri H, Karaaslan C, Teper Y et al (2009) Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J 23:3865–3873

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Errico M, Riccioni T, Iyer S et al (2004) Identification of placenta growth factor determinants for binding and activation of Flt-1 receptor. J Biol Chem 279:43929–43939

    Article  CAS  PubMed  Google Scholar 

  • Fang L, Choi SH, Baek JS et al (2013) Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature 498:118–122

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fearnley GW, Odell AF, Latham AM et al (2014) VEGF-A isoforms differentially regulate ATF-2-dependent VCAM-1 gene expression and endothelial-leukocyte interactions. Mol Biol Cell 25:2509–21

  • Feener EP, King GL (1997) Vascular dysfunction in diabetes mellitus. Lancet 350:SI9–SI13

  • Ferrara N (2010) Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action. Mol Biol Cell 21:687–690

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438:967–974

    Article  CAS  PubMed  Google Scholar 

  • Ferrara N, Carver-Moore K, Chen H et al (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439–442

    Article  CAS  PubMed  Google Scholar 

  • Fijalkowska I, Xu W, Comhair SA et al (2010) Hypoxia inducible-factor1alpha regulates the metabolic shift of pulmonary hypertensive endothelial cells. Am J Pathol 176:1130–1138

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Flyvbjerg A, Dagnaes-Hansen F, De Vriese AS et al (2002) Amelioration of long-term renal changes in obese type 2 diabetic mice by a neutralizing vascular endothelial growth factor antibody. Diabetes 51:3090–3094

    Article  CAS  PubMed  Google Scholar 

  • Fontanella C, Ongaro E, Bolzonello S et al (2014) Clinical advances in the development of novel VEGFR2 inhibitors. Ann Transl Med 2:123

    PubMed Central  PubMed  Google Scholar 

  • Fulton D, Gratton JP, McCabe TJ et al (1999) Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 399:597–601

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Giordano FJ, Gerber HP, Williams SP et al (2001) A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad Sci USA 98:5780–5785

  • Grunewald FS, Prota AE, Giese A et al (2010) Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling. Biochim Biophys Acta 1804:567–580

    Article  PubMed  Google Scholar 

  • Hagberg CE, Falkevall A, Wang X et al (2010) Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature 464:917–921

    Article  CAS  PubMed  Google Scholar 

  • Han SW, Kim GW, Seo JS et al (2004) VEGF gene polymorphisms and susceptibility to rheumatoid arthritis. Rheumatology 43:1173–1177

  • Heissig B, Hattori K, Dias S et al (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109:625–637

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Heitzer T, Schlinzig T, Krohn K et al (2001) Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 104:2673–2678

    Article  CAS  PubMed  Google Scholar 

  • Hiratsuka S, Maru Y, Okada A et al (2001) Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Cancer Res 61:1207–1213

    CAS  PubMed  Google Scholar 

  • Holmqvist K, Cross M, Riley D et al (2003) The Shb adaptor protein causes Src-dependent cell spreading and activation of focal adhesion kinase in murine brain endothelial cells. Cell Signal 15:171–179

    Article  CAS  PubMed  Google Scholar 

  • Hornig B, Arakawa N, Kohler C et al (1998) Vitamin C improves endothelial function of conduit arteries in patients with chronic heart failure. Circulation 97:363–368

    Article  CAS  PubMed  Google Scholar 

  • Jang C, Arany Z (2013) Metabolism: sweet enticements to move. Nature 500:409–411

    Article  CAS  PubMed  Google Scholar 

  • Jin F, Hagemann N, Brockmeier U et al (2013) LDL attenuates VEGF-induced angiogenesis via mechanisms involving VEGFR2 internalization and degradation following endosome-trans-golgi network trafficking. Angiogenesis 16:625–637

    Article  CAS  PubMed  Google Scholar 

  • Kawamoto A, Iwasaki H, Kusano K et al (2006) Cd34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells. Circulation 114:2163–2169

    Article  PubMed  Google Scholar 

  • Kendall RL, Thomas KA (1993) Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci USA 90:10705–10709

  • Kendall RL, Rutledge RZ, Mao X et al (1999) Vascular endothelial growth factor receptor KDR tyrosine kinase activity is increased by autophosphorylation of two activation loop tyrosine residues. J Biol Chem 274:6453–6460

    Article  CAS  PubMed  Google Scholar 

  • Koch S, Claesson-Welsh L (2012) Signal transduction by vascular endothelial growth factor receptors. Cold Spring Harb Perspect Med 2:a006502

    Article  PubMed Central  PubMed  Google Scholar 

  • Koch S, Tugues S, Li X et al (2011) Signal transduction by vascular endothelial growth factor receptors. Biochem J 437:169–183

    Article  CAS  PubMed  Google Scholar 

  • Lamalice L, Houle F, Huot J (2006) Phosphorylation of Tyr1214 within VEGFR-2 triggers the recruitment of Nck and activation of Fyn leading to SAPK2/p38 activation and endothelial cell migration in response to VEGF. J Biol Chem 281:34009–34020

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Chen TT, Barber CL et al (2007) Autocrine VEGF signaling is required for vascular homeostasis. Cell 130:691–703

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Leopold JA, Walker J, Scribner AW et al (2003) Glucose-6-phosphate dehydrogenase modulates vascular endothelial growth factor-mediated angiogenesis. J Biol Chem 278:32100–32106

    Article  CAS  PubMed  Google Scholar 

  • Li X, Tjwa M, Van Hove I et al (2008) Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium. Arterioscler Thromb Vasc Biol 28:1614–1620

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Locasale JW, Cantley LC (2011) Metabolic flux and the regulation of mammalian cell growth. Cell Metab 14:443–451

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maher ER, Neumann HP, Richard S (2011) Von hippel-lindau disease: a clinical and scientific review. Eur J Hum Genet 19:617–623

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Markowska AI, Jefferies KC, Panjwani N (2011) Galectin-3 protein modulates cell surface expression and activation of vascular endothelial growth factor receptor 2 in human endothelial cells. J Biol Chem 286:29913–29921

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Matsumoto T, Bohman S, Dixelius J et al (2005) VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis. EMBO J 24:2342–2353

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Meadows KN, Bryant P, Pumiglia K (2001) Vascular endothelial growth factor induction of the angiogenic phenotype requires ras activation. J Biol Chem 276:49289–49298

    Article  CAS  PubMed  Google Scholar 

  • Mittar S, Ulyatt C, Howell GJ et al (2009) VEGFR1 receptor tyrosine kinase localization to the Golgi apparatus is calcium-dependent. Exp Cell Res 315:877–889

    Article  CAS  PubMed  Google Scholar 

  • Murohara T, Asahara T, Silver M et al (1998) Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest 101:2567–2578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nakagawa T (2007) Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an explanation for the paradoxical effects of VEGF in renal disease. Am J Physiol Renal Physiol 292:F1665–F1672

    Article  CAS  PubMed  Google Scholar 

  • Olofsson B, Korpelainen E, Pepper MS et al (1998) Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci USA 95:11709–11714

  • Orlic D, Kajstura J, Chimenti S et al (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 98:10344–10349

  • Paleolog EM (2002) Angiogenesis in rheumatoid arthritis. Arthritis Res 4:S81–S90

  • Pan S, World CJ, Kovacs CJ et al (2009) Glucose 6-phosphate dehydrogenase is regulated through c-Src-mediated tyrosine phosphorylation in endothelial cells. Arterioscler Thromb Vasc Biol 29:895–901

    Article  CAS  PubMed  Google Scholar 

  • Rahimi N (2006) VEGFR-1 and VEGFR-2: two non-identical twins with a unique physiognomy. Front Biosci 11:818–829

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Raikwar NS, Liu KZ, Thomas CP (2013) Protein kinase C regulates Flt1 abundance and stimulates its cleavage in vascular endothelial cells with the release of a soluble PlGF/VEGF antagonist. Exp Cell Res 319:2578–2587

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ray D, Mishra M, Ralph S et al (2004) Association of the VEGF gene with proliferative diabetic retinopathy but not proteinuria in diabetes. Diabetes 53:861–864

    Article  CAS  PubMed  Google Scholar 

  • Reihill JA, Ewart MA, Salt IP (2011) The role of AMP-activated protein kinase in the functional effects of vascular endothelial growth factor-A and -B in human aortic endothelial cells. Vasc Cell 3:9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Robinson CJ, Stringer SE (2001) The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 114:853–865

    CAS  PubMed  Google Scholar 

  • Roskoski R Jr (2007) Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol 62:179–213

    Article  PubMed  Google Scholar 

  • Ruan GX, Kazlauskas A (2013) Lactate engages receptor tyrosine kinases Axl, Tie2, and vascular endothelial growth factor receptor 2 to activate phosphoinositide 3-kinase/Akt and promote angiogenesis. J Biol Chem 288:21161–21172

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ryu S, Lee JH, Kim SI (2006) IL-17 increased the production of vascular endothelial growth factor in rheumatoid arthritis synoviocytes. Clin Rheumatol 25:16–20

    Article  CAS  PubMed  Google Scholar 

  • Santos CR, Schulze A (2012) Lipid metabolism in cancer. FEBS J 279:2610–2623

    Article  CAS  PubMed  Google Scholar 

  • Sasso FC, Torella D, Carbonara O et al (2005) Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease. J Am Coll Cardiol 46:827–834

    Article  CAS  PubMed  Google Scholar 

  • Sawamiphak S, Seidel S, Essmann CL et al (2010) Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 465:487–491

    Article  CAS  PubMed  Google Scholar 

  • Sela S, Itin A, Natanson-Yaron S et al (2008) A novel human-specific soluble vascular endothelial growth factor receptor 1: cell-type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia. Circ Res 102:1566–1574

    Article  CAS  PubMed  Google Scholar 

  • Shalaby F, Rossant J, Yamaguchi TP et al (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376:62–66

    Article  CAS  PubMed  Google Scholar 

  • Sharma K, Sharma NK, Anand A (2014) Why amd is a disease of ageing and not of development: mechanisms and insights. Front Aging Neurosci 6:151

    Article  PubMed Central  PubMed  Google Scholar 

  • Shen L, Gao Y, Qian J et al (2011) A novel mechanism for endothelial progenitor cells homing: the SDF-1/CXCR4-rac pathway may regulate endothelial progenitor cells homing through cellular polarization. Med Hypotheses 76:256–258

    Article  CAS  PubMed  Google Scholar 

  • Simons M (2005) Angiogenesis, arteriogenesis, and diabetes: paradigm reassessed? J Am Coll Cardiol 46:835–837

    Article  PubMed  Google Scholar 

  • Suganthalakshmi B, Anand R, Kim R et al (2006) Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy. Mol Vis 12:336–341

    CAS  PubMed  Google Scholar 

  • Sydorova M, Lee MS (2005) Vascular endothelial growth factor levels in vitreous and serum of patients with either proliferative diabetic retinopathy or proliferative vitreoretinopathy. Ophthalmic Res 37:188–190

    Article  CAS  PubMed  Google Scholar 

  • Tammali R, Reddy AB, Srivastava SK et al (2011) Inhibition of aldose reductase prevents angiogenesis in vitro and in vivo. Angiogenesis 14:209–221

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tang JM, Wang JN, Zhang L et al (2011) VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart. Cardiovasc Res 91:402–411

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tang WH, Martin KA, Hwa J (2012) Aldose reductase, oxidative stress, and diabetic mellitus. Front Pharmacol 3:87

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tchaikovski V, Fellbrich G, Waltenberger J (2008) The molecular basis of VEGFR-1 signal transduction pathways in primary human monocytes. Arterioscler Thromb Vasc Biol 28:322–328

    Article  CAS  PubMed  Google Scholar 

  • Tchaikovski V, Olieslagers S, Bohmer FD et al (2009) Diabetes mellitus activates signal transduction pathways resulting in vascular endothelial growth factor resistance of human monocytes. Circulation 120:150–159

    Article  CAS  PubMed  Google Scholar 

  • Ulyatt C, Walker J, Ponnambalam S (2011) Hypoxia differentially regulates VEGFR1 and VEGFR2 levels and alters intracellular signaling and cell migration in endothelial cells. Biochem Biophys Res Commun 404:774–779

    Article  CAS  PubMed  Google Scholar 

  • Urbanek K, Rota M, Cascapera S et al (2005) Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 97:663–673

    Article  CAS  PubMed  Google Scholar 

  • Uthra S, Raman R, Mukesh BN et al (2008) Association of VEGF gene polymorphisms with diabetic retinopathy in a south indian cohort. Ophthalmic Genet 29:11–15

    Article  CAS  PubMed  Google Scholar 

  • Vaisman N, Gospodarowicz D, Neufeld G (1990) Characterization of the receptors for vascular endothelial growth factor. J Biol Chem 265:19461–19466

    CAS  PubMed  Google Scholar 

  • van der Meer P, De Boer RA, White HL et al (2005) The vegf +405 cc promoter polymorphism is associated with an impaired prognosis in patients with chronic heart failure: a MERIT-HF substudy. J Card Fail 11:279–284

    Article  PubMed  Google Scholar 

  • Vizan P, Sanchez-Tena S, Alcarraz-Vizan G et al (2009) Characterization of the metabolic changes underlying growth factor angiogenic activation: identification of new potential therapeutic targets. Carcinogenesis 30:946–952

    Article  CAS  PubMed  Google Scholar 

  • Waltenberger J (2009) VEGF resistance as a molecular basis to explain the angiogenesis paradox in diabetes mellitus. Biochem Soc Trans 37:1167–1170

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Heilig KO, Minto AW et al (2010) Nephron-deficient Fvb mice develop rapidly progressive renal failure and heavy albuminuria involving excess glomerular GLUT1 and VEGF. Lab Invest 90:83–97

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Warren CM, Ziyad S, Briot A et al (2014) A ligand-independent VEGFR2 signaling pathway limits angiogenic responses in diabetes. Sci Signal 7:ra1

    Article  PubMed Central  PubMed  Google Scholar 

  • Watson CJ, Webb NJ, Bottomley MJ et al (2000) Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 12:1232–1235

    Article  CAS  PubMed  Google Scholar 

  • Wei X, Schneider JG, Shenouda SM et al (2011) De novo lipogenesis maintains vascular homeostasis through endothelial nitric-oxide synthase (eNOS) palmitoylation. J Biol Chem 286:2933–2945

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Werner GS, Richartz BM, Heinke S et al (2003) Impaired acute collateral recruitment as a possible mechanism for increased cardiac adverse events in patients with diabetes mellitus. Eur Heart J 24:1134–1142

    Article  PubMed  Google Scholar 

  • Wiesmann C, Fuh G, Christinger HW et al (1997) Crystal structure at 1.7 a resolution of VEGF in complex with domain 2 of the Flt-1 receptor. Cell 91:695–704

    Article  CAS  PubMed  Google Scholar 

  • Yeh WL, Lin CJ, Fu WM (2008) Enhancement of glucose transporter expression of brain endothelial cells by vascular endothelial growth factor derived from glioma exposed to hypoxia. Mol Pharmacol 73:170–177

    Article  CAS  PubMed  Google Scholar 

  • Yu Y, Hulmes JD, Herley MT et al (2001) Direct identification of a major autophosphorylation site on vascular endothelial growth factor receptor Flt-1 that mediates phosphatidylinositol 3′-kinase binding. Biochem J 358:465–472

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zeiher AM, Drexler H, Saurbier B et al (1993) Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension. J Clin Invest 92:652–662

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Work in our laboratories is supported by PhD studentships from the British Heart Foundation (G.A.S.), Heart Research UK (G.W.F.), European Research Council Fellowship, British Heart Foundation and Medical Research Council (S.B.W.).

Compliance with Ethics Guidelines

ᅟ

Conflict of interest

None.

Human or animal

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Endothelial Cell Biology Unit, School of Molecular & Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK

    Gina A. Smith, Gareth W. Fearnley & Sreenivasan Ponnambalam

  2. School of Biomedical Sciences, LIGHT Laboratories, University of Leeds, Leeds, LS2 9JT, UK

    Michael A. Harrison

  3. School of Molecular & Cellular Biology & Biomedical Health Research Centre, Astbury Building, University of Leeds, Leeds, LS2 9JT, UK

    Darren C. Tomlinson

  4. Leeds Institute of Cardiovascular & Metabolic Medicine, Faculty of Medicine & Health, LIGHT Laboratories, University of Leeds, Leeds, LS2 9JT, UK

    Stephen B. Wheatcroft

Authors
  1. Gina A. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gareth W. Fearnley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael A. Harrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Darren C. Tomlinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stephen B. Wheatcroft
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sreenivasan Ponnambalam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sreenivasan Ponnambalam.

Additional information

Communicated by: Niels Gregersen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Smith, G.A., Fearnley, G.W., Harrison, M.A. et al. Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease. J Inherit Metab Dis 38, 753–763 (2015). https://doi.org/10.1007/s10545-015-9838-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-015-9838-4

Keywords

Search

Navigation