Skip to main content
SpringerLink
Log in

Angiogenesis: General Concepts

  • Chapter
  • First Online:
Book cover Angiogenesis-Based Dermatology

  • 564 Accesses

Abstract

Blood vessels are involved in the regulation and maintenance of all tissues and are key players in the development of disease. In adults, the destabilization of blood vessels, often seen in association with induced vascular growth or remodeling, are driving pathological phenotypes such as inflammation, edema, deregulated tissue growth/regeneration and systemic dissemination of tumor cells leading to metastasis or bacteria/bacterial products leading to sepsis. In order to target pathological blood vessel growth (angiogenesis) or destabilization as means to treat human disease, it is important to understand how blood vessels are structured, function, the mechanisms regulating physiological and pathological angiogenesis and how these processes differ. Here we will present some general concepts related to vascular biology and angiogenesis, as well as lymphangiogenesis, i.e. the growth of the lymphatic vascularture. The aim of this chapter is to provide a foundation for understanding mechanisms of angiogenesis in health and disease, which can be applied more specifically to various aspects of skin biology and pathologies in other chapters. We will also identify and discuss aspects of angiogenesis which remain poorly understood and present suggestions for further research in this area.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9:653–60.

    Article  CAS  PubMed  Google Scholar 

  2. Cao Y, Arbiser J, D’Amato RJ, D’Amore PA, Ingber DE, Kerbel R, Klagsbrun M, Lim S, Moses MA, Zetter B, Dvorak H, Langer R. Forty-year journey of angiogenesis translational research. Sci Transl Med. 2011;3:114rv113.

    Google Scholar 

  3. Crivellato E, Ribatti D. Aristotle: the first student of angiogenesis. Leukemia. 2006;20:1209–10.

    Article  CAS  PubMed  Google Scholar 

  4. Natale G, Bocci G, Lenzi P. Looking for the word “angiogenesis” in the history of health sciences: from ancient times to the first decades of the twentieth century. World J Surg. 2016. doi:10.1007/s00268-016-3680-1

  5. Cimpean AM, Ribatti D, Raica M. A brief history of angiogenesis assays. Int J Dev Biol. 2011;55:377–82.

    Article  PubMed  Google Scholar 

  6. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989;161:851–8.

    Article  CAS  PubMed  Google Scholar 

  7. Gospodarowicz D, Abraham JA, Schilling J. Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc Natl Acad Sci U S A. 1989;86:7311–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Vaisman N, Gospodarowicz D, Neufeld G. Characterization of the receptors for vascular endothelial growth factor. J Biol Chem. 1990;265:19461–6.

    CAS  PubMed  Google Scholar 

  9. Plouet J, Moukadiri H. Characterization of the receptor to vasculotropin on bovine adrenal cortex-derived capillary endothelial cells. J Biol Chem. 1990;265:22071–4.

    CAS  PubMed  Google Scholar 

  10. de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992;255:989–91.

    Article  PubMed  Google Scholar 

  11. Terman BI, Dougher-Vermazen M, Carrion ME, Dimitrov D, Armellino DC, Gospodarowicz D, Bohlen P. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun. 1992;187:1579–86.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, Bruggen N, Chopp M. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest. 2000;106:829–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Banquet S, Gomez E, Nicol L, Edwards-Levy F, Henry JP, Cao R, Schapman D, Dautreaux B, Lallemand F, Bauer F, Cao Y, Thuillez C, Mulder P, Richard V, Brakenhielm E. Arteriogenic therapy by intramyocardial sustained delivery of a novel growth factor combination prevents chronic heart failure. Circulation. 2011;124:1059–69.

    Article  PubMed  Google Scholar 

  14. Cao Y. Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev Drug Discov. 2010;9:107–15.

    Article  CAS  PubMed  Google Scholar 

  15. Gustafsson T, Kraus WE. Exercise-induced angiogenesis-related growth and transcription factors in skeletal muscle, and their modification in muscle pathology. Front Biosci. 2001;6:D75–89.

    CAS  PubMed  Google Scholar 

  16. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–6.

    Article  CAS  PubMed  Google Scholar 

  17. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380:435–9.

    Article  CAS  PubMed  Google Scholar 

  18. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003;161:1163–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jensen LD, Nakamura M, Brautigam L, Li X, Liu Y, Samani NJ, Cao Y. VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish. Proc Natl Acad Sci U S A. 2015;112:E5944–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Risau W. Mechanisms of angiogenesis. Nature. 1997;386:671–4.

    Article  CAS  PubMed  Google Scholar 

  21. Cao R, Brakenhielm E, Pawliuk R, Wariaro D, Post MJ, Wahlberg E, Leboulch P, Cao Y. Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2. Nat Med. 2003;9:604–13.

    Article  CAS  PubMed  Google Scholar 

  22. Cao R, Ji H, Yang Y, Cao Y. Collaborative effects between the TNFalpha-TNFR1-macrophage axis and the VEGF-C-VEGFR3 signaling in lymphangiogenesis and metastasis. Oncoimmunol. 2015;4:e989777.

    Article  CAS  Google Scholar 

  23. Cao R, Ji H, Feng N, Zhang Y, Yang X, Andersson P, Sun Y, Tritsaris K, Hansen AJ, Dissing S, Cao Y. Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis. Proc Natl Acad Sci U S A. 2012;109:15894–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cao R, Bjorndahl MA, Religa P, Clasper S, Garvin S, Galter D, Meister B, Ikomi F, Tritsaris K, Dissing S, Ohhashi T, Jackson DG, Cao Y. PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell. 2004;6:333–45.

    Article  CAS  PubMed  Google Scholar 

  25. Nissen LJ, Cao R, Hedlund EM, Wang Z, Zhao X, Wetterskog D, Funa K, Brakenhielm E, Cao Y. Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. J Clin Invest. 2007;117:2766–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ji H, Cao R, Yang Y, Zhang Y, Iwamoto H, Lim S, Nakamura M, Andersson P, Wang J, Sun Y, Dissing S, He X, Yang X, Cao Y. TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling. Nat Commun. 2014;5:4944.

    Article  CAS  PubMed  Google Scholar 

  27. Ueki N, Nakazato M, Ohkawa T, Ikeda T, Amuro Y, Hada T, Higashino K. Excessive production of transforming growth-factor beta 1 can play an important role in the development of tumorigenesis by its action for angiogenesis: validity of neutralizing antibodies to block tumor growth. Biochim Biophys Acta. 1992;1137:189–96.

    Article  CAS  PubMed  Google Scholar 

  28. Pan B, Shen J, Cao J, Zhou Y, Shang L, Jin S, Cao S, Che D, Liu F, Yu Y. Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer. Sci Report. 2015;5:16053.

    Article  CAS  Google Scholar 

  29. Wang J, Wang Y, Wang S, Cai J, Shi J, Sui X, Cao Y, Huang W, Chen X, Cai Z, Li H, Bardeesi AS, Zhang B, Liu M, Song W, Wang M, Xiang AP. Bone marrow-derived mesenchymal stem cell-secreted IL-8 promotes the angiogenesis and growth of colorectal cancer. Oncotarget. 2015;6:42825–37.

    PubMed  PubMed Central  Google Scholar 

  30. Yang Y, Andersson P, Hosaka K, Zhang Y, Cao R, Iwamoto H, Yang X, Nakamura M, Wang J, Zhuang R, Morikawa H, Xue Y, Braun H, Beyaert R, Samani N, Nakae S, Hams E, Dissing S, Fallon PG, Langer R, Cao Y. The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages. Nat Commun. 2016;7:11385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ferrara N. Role of myeloid cells in vascular endothelial growth factor-independent tumor angiogenesis. Curr Opin Hematol. 2010;17:219–24.

    CAS  PubMed  Google Scholar 

  32. Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol. 2012;196:395–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cao Y. Opinion: emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis. Nat Rev Cancer. 2005;5:735–43.

    Article  CAS  PubMed  Google Scholar 

  34. Vanhollebeke B, Stone OA, Bostaille N, Cho C, Zhou Y, Maquet E, Gauquier A, Cabochette P, Fukuhara S, Mochizuki N, Nathans J, Stainier DY. Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/beta-catenin pathway during brain angiogenesis. Elife. 2015;4:e06489.

    Article  PubMed Central  CAS  Google Scholar 

  35. Zhou Y, Nathans J. Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling. Dev Cell. 2014;31:248–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cao R, Brakenhielm E, Wahlestedt C, Thyberg J, Cao Y. Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc Natl Acad Sci U S A. 2001;98:6390–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Brakenhielm E, Cao R, Gao B, Angelin B, Cannon B, Parini P, Cao Y. Angiogenesis inhibitor, TNP-470, prevents diet-induced and genetic obesity in mice. Circ Res. 2004;94:1579–88.

    Article  CAS  PubMed  Google Scholar 

  38. Xue Y, Petrovic N, Cao R, Larsson O, Lim S, Chen S, Feldmann HM, Liang Z, Zhu Z, Nedergaard J, Cannon B, Cao Y. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab. 2009;9:99–109.

    Article  CAS  PubMed  Google Scholar 

  39. Thomas PR, Nash GB, Dormandy JA. White cell accumulation in dependent legs of patients with venous hypertension: a possible mechanism for trophic changes in the skin. Br Med J (Clin Res Ed). 1988;296:1693–5.

    Article  CAS  Google Scholar 

  40. Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE, Cohen MS, Turner R, et al. Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci U S A. 1992;89:5675–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Stacy MR, Caracciolo CM, Qiu M, Pal P, Varga T, Constable RT, Sinusas AJ. Comparison of regional skeletal muscle tissue oxygenation in college athletes and sedentary control subjects using quantitative BOLD MR imaging. Phys Rep. 2016;4:1–10. doi:10.14814/phy2.12903

  42. Iadecola C, Nedergaard M. Glial regulation of the cerebral microvasculature. Nat Neurosci. 2007;10:1369–76.

    Article  CAS  PubMed  Google Scholar 

  43. Wei HS, Kang H, Rasheed IY, Zhou S, Lou N, Gershteyn A, McConnell ED, Wang Y, Richardson KE, Palmer AF, Xu C, Wan J, Nedergaard M. Erythrocytes are oxygen-sensing regulators of the cerebral microcirculation. Neuron. 2016;91:851–62.

    Article  CAS  PubMed  Google Scholar 

  44. During MJ, Liu X, Huang W, Magee D, Slater A, McMurphy T, Wang C, Cao L. Adipose VEGF links the white-to-brown fat switch with environmental, genetic, and pharmacological stimuli in male mice. Endocrinology. 2015;156:2059–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cao Y. Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity. Cell Metab. 2013;18:478–89.

    Article  CAS  PubMed  Google Scholar 

  46. Xue Y, Cao R, Nilsson D, Chen S, Westergren R, Hedlund EM, Martijn C, Rondahl L, Krauli P, Walum E, Enerback S, Cao Y. FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue. Proc Natl Acad Sci U S A. 2008;105:10167–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. McCall AL, van Bueren AM, Huang L, Stenbit A, Celnik E, Charron MJ. Forebrain endothelium expresses GLUT4, the insulin-responsive glucose transporter. Brain Res. 1997;744:318–26.

    Article  CAS  PubMed  Google Scholar 

  48. Stenman JM, Rajagopal J, Carroll TJ, Ishibashi M, McMahon J, McMahon AP. Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature. Science. 2008;322:1247–50.

    Article  CAS  PubMed  Google Scholar 

  49. Scholzen TE, Brzoska T, Kalden DH, Hartmeyer M, Fastrich M, Luger TA, Armstrong CA, Ansel JC. Expression of functional melanocortin receptors and proopiomelanocortin peptides by human dermal microvascular endothelial cells. Ann N Y Acad Sci. 1999;885:239–53.

    Article  CAS  PubMed  Google Scholar 

  50. Russell KS, Haynes MP, Sinha D, Clerisme E, Bender JR. Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proc Natl Acad Sci U S A. 2000;97:5930–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Reiss Y, Engelhardt B. T cell interaction with ICAM-1-deficient endothelium in vitro: transendothelial migration of different T cell populations is mediated by endothelial ICAM-1 and ICAM-2. Int Immunol. 1999;11:1527–39.

    Article  CAS  PubMed  Google Scholar 

  52. Gonzalez-Alonso J. Human thermoregulation and the cardiovascular system. Exp Physiol. 2012;97:340–6.

    Article  CAS  PubMed  Google Scholar 

  53. Daanen HA, Van Marken Lichtenbelt WD. Human whole body cold adaptation. Temperature (Austin). 2016;3:104–18.

    Article  Google Scholar 

  54. Gerhart-Hines Z, Feng D, Emmett MJ, Everett LJ, Loro E, Briggs ER, Bugge A, Hou C, Ferrara C, Seale P, Pryma DA, Khurana TS, Lazar MA. The nuclear receptor Rev-erbalpha controls circadian thermogenic plasticity. Nature. 2013;503:410–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;441:1075–9.

    Article  CAS  PubMed  Google Scholar 

  56. Ottone C, Krusche B, Whitby A, Clements M, Quadrato G, Pitulescu ME, Adams RH, Parrinello S. Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells. Nat Cell Biol. 2014;16:1045–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gomez-Gaviro MV, Lovell-Badge R, Fernandez-Aviles F, Lara-Pezzi E. The vascular stem cell niche. J Cardiovasc Transl Res. 2012;5:618–30.

    Article  PubMed  Google Scholar 

  58. Gupta RK, Mepani RJ, Kleiner S, Lo JC, Khandekar MJ, Cohen P, Frontini A, Bhowmick DC, Ye L, Cinti S, Spiegelman BM. Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Metab. 2012;15:230–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hughes R, Qian BZ, Rowan C, Muthana M, Keklikoglou I, Olson OC, Tazzyman S, Danson S, Addison C, Clemons M, Gonzalez-Angulo AM, Joyce JA, De Palma M, Pollard JW, Lewis CE. Perivascular M2 macrophages stimulate tumor relapse after chemotherapy. Cancer Res. 2015;75:3479–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hislop AA. Airway and blood vessel interaction during lung development. J Anat. 2002;201:325–34.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Sequeira Lopez ML, Gomez RA. Development of the renal arterioles. J Am Soc Nephrol. 2011;22:2156–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev Cell. 2010;18:175–89.

    Article  CAS  PubMed  Google Scholar 

  63. Ekstrand AJ, Cao R, Bjorndahl M, Nystrom S, Jonsson-Rylander AC, Hassani H, Hallberg B, Nordlander M, Cao Y. Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing. Proc Natl Acad Sci U S A. 2003;100:6033–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Alvarez Y, Astudillo O, Jensen L, Reynolds AL, Waghorne N, Brazil DP, Cao Y, O’Connor JJ, Kennedy BN. Selective inhibition of retinal angiogenesis by targeting PI3 kinase. PLoS One. 2009;4:e7867.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Korzh S, Pan X, Garcia-Lecea M, Winata CL, Pan X, Wohland T, Korzh V, Gong Z. Requirement of vasculogenesis and blood circulation in late stages of liver growth in zebrafish. BMC Dev Biol. 2008;8:84.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Majumdar A, Drummond IA. Podocyte differentiation in the absence of endothelial cells as revealed in the zebrafish avascular mutant, cloche. Dev Genet. 1999;24:220–9.

    Article  CAS  PubMed  Google Scholar 

  67. Paulsson M. Basement membrane proteins: structure, assembly, and cellular interactions. Crit Rev Biochem Mol Biol. 1992;27:93–127.

    Article  CAS  PubMed  Google Scholar 

  68. Zhang Y, Yang Y, Hosaka K, Huang G, Zang J, Chen F, Zhang Y, Samani NJ, Cao Y. Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy. Proc Natl Acad Sci U S A. 2016;113:4158–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Birbrair A, Zhang T, Files DC, Mannava S, Smith T, Wang ZM, Messi ML, Mintz A, Delbono O. Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner. Stem Cell Res Ther. 2014;5:122.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Birbrair A, Zhang T, Wang ZM, Messi ML, Mintz A, Delbono O. Pericytes at the intersection between tissue regeneration and pathology. Clin Sci (Lond). 2015;128:81–93.

    Article  CAS  Google Scholar 

  71. Geevarghese A, Herman IM. Pericyte-endothelial crosstalk: implications and opportunities for advanced cellular therapies. Transl Res. 2014;163:296–306.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Dahl Ejby Jensen L, Cao R, Hedlund EM, Soll I, Lundberg JO, Hauptmann G, Steffensen JF, Cao Y. Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish. Proc Natl Acad Sci U S A. 2009;106:18408–13.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Jensen LD, Rouhi P, Cao Z, Lanne T, Wahlberg E, Cao Y. Zebrafish models to study hypoxia-induced pathological angiogenesis in malignant and nonmalignant diseases. Birth Defects Res C Embryo Today. 2011;93:182–93.

    Article  CAS  PubMed  Google Scholar 

  74. Gordan R, Gwathmey JK, Xie LH. Autonomic and endocrine control of cardiovascular function. World J Cardiol. 2015;7:204–14.

    PubMed  PubMed Central  Google Scholar 

  75. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31:986–1000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Keith IM. The role of endogenous lung neuropeptides in regulation of the pulmonary circulation. Physiol Res. 2000;49:519–37.

    CAS  PubMed  Google Scholar 

  77. Heil M, Schaper W. Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ Res. 2004;95:449–58.

    Article  CAS  PubMed  Google Scholar 

  78. Galie PA, Nguyen DH, Choi CK, Cohen DM, Janmey PA, Chen CS. Fluid shear stress threshold regulates angiogenic sprouting. Proc Natl Acad Sci U S A. 2014;111:7968–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty KE, Lawson ND. MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature. 2010;464:1196–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lawson ND, Vogel AM, Weinstein BM. sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation. Dev Cell. 2002;3:127–36.

    Article  CAS  PubMed  Google Scholar 

  81. Gore AV, Monzo K, Cha YR, Pan W, Weinstein BM. Vascular development in the zebrafish. Cold Spring Harb Perspect Med. 2012;2:a006684.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Kamei M, Saunders WB, Bayless KJ, Dye L, Davis GE, Weinstein BM. Endothelial tubes assemble from intracellular vacuoles in vivo. Nature. 2006;442:453–6.

    Article  CAS  PubMed  Google Scholar 

  83. Lammert E, Axnick J. Vascular lumen formation. Cold Spring Harb Perspect Med. 2012;2:a006619.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Gritz E, Hirschi KK. Specification and function of hemogenic endothelium during embryogenesis. Cell Mol Life Sci. 2016;73:1547–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Herbert SP, Huisken J, Kim TN, Feldman ME, Houseman BT, Wang RA, Shokat KM, Stainier DY. Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation. Science. 2009;326:294–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Isogai S, Horiguchi M, Weinstein BM. The vascular anatomy of the developing zebrafish: an atlas of embryonic and early larval development. Dev Biol. 2001;230:278–301.

    Article  CAS  PubMed  Google Scholar 

  87. Rundhaug JE. Matrix metalloproteinases and angiogenesis. J Cell Mol Med. 2005;9:267–85.

    Article  CAS  PubMed  Google Scholar 

  88. Siekmann AF, Lawson ND. Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature. 2007;445:781–4.

    Article  CAS  PubMed  Google Scholar 

  89. Hellstrom M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela-Arispe ML, Kalen M, Gerhardt H, Betsholtz C. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 2007;445:776–80.

    Article  PubMed  CAS  Google Scholar 

  90. Cao R, Jensen LD, Soll I, Hauptmann G, Cao Y. Hypoxia-induced retinal angiogenesis in zebrafish as a model to study retinopathy. PLoS One. 2008;3:e2748.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Jakobsson L, Franco CA, Bentley K, Collins RT, Ponsioen B, Aspalter IM, Rosewell I, Busse M, Thurston G, Medvinsky A, Schulte-Merker S, Gerhardt H. Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat Cell Biol. 2010;12:943–53.

    Article  CAS  PubMed  Google Scholar 

  92. Herwig L, Blum Y, Krudewig A, Ellertsdottir E, Lenard A, Belting HG, Affolter M. Distinct cellular mechanisms of blood vessel fusion in the zebrafish embryo. Curr Biol. 2011;21:1942–8.

    Article  CAS  PubMed  Google Scholar 

  93. Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, Peri F, Wilson SW, Ruhrberg C. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood. 2010;116:829–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lindblom P, Gerhardt H, Liebner S, Abramsson A, Enge M, Hellstrom M, Backstrom G, Fredriksson S, Landegren U, Nystrom HC, Bergstrom G, Dejana E, Ostman A, Lindahl P, Betsholtz C. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev. 2003;17:1835–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Krueger J, Liu D, Scholz K, Zimmer A, Shi Y, Klein C, Siekmann A, Schulte-Merker S, Cudmore M, Ahmed A, le Noble F. Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo. Development. 2011;138:2111–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res. 2007;100:782–94.

    Article  CAS  PubMed  Google Scholar 

  97. Adams RH, Eichmann A. Axon guidance molecules in vascular patterning. Cold Spring Harb Perspect Biol. 2010;2:a001875.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Torres-Vazquez J, Gitler AD, Fraser SD, Berk JD, Van NP, Fishman MC, Childs S, Epstein JA, Weinstein BM. Semaphorin-plexin signaling guides patterning of the developing vasculature. Dev Cell. 2004;7:117–23.

    Article  CAS  PubMed  Google Scholar 

  99. Jung B, Obinata H, Galvani S, Mendelson K, Ding BS, Skoura A, Kinzel B, Brinkmann V, Rafii S, Evans T, Hla T. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development. Dev Cell. 2012;23:600–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ribatti D, Nico B, Crivellato E. The role of pericytes in angiogenesis. Int J Dev Biol. 2011;55:261–8.

    Article  CAS  PubMed  Google Scholar 

  101. Burri PH, Djonov V. Intussusceptive angiogenesis--the alternative to capillary sprouting. Mol Asp Med. 2002;23:S1–27.

    Article  Google Scholar 

  102. Gianni-Barrera R, Trani M, Fontanellaz C, Heberer M, Djonov V, Hlushchuk R, Banfi A. VEGF over-expression in skeletal muscle induces angiogenesis by intussusception rather than sprouting. Angiogenesis. 2013;16:123–36.

    Article  CAS  PubMed  Google Scholar 

  103. Dimova I, Hlushchuk R, Makanya A, Styp-Rekowska B, Ceausu A, Flueckiger S, Lang S, Semela D, Le Noble F, Chatterjee S, Djonov V. Inhibition of Notch signaling induces extensive intussusceptive neo-angiogenesis by recruitment of mononuclear cells. Angiogenesis. 2013;16:921–37.

    Article  CAS  PubMed  Google Scholar 

  104. Mukwaya A, Peebo B, Xeroudaki M, Ali Z, Lennikov A, Jensen L, Lagali N. Factors regulating capillary remodeling in a reversible model of inflammatory corneal angiogenesis. Sci Report. 2016;6:32137.

    Article  CAS  Google Scholar 

  105. Djonov V, Schmid M, Tschanz SA, Burri PH. Intussusceptive angiogenesis: its role in embryonic vascular network formation. Circ Res. 2000;86:286–92.

    Article  CAS  PubMed  Google Scholar 

  106. Makanya AN, Hlushchuk R, Baum O, Velinov N, Ochs M, Djonov V. Microvascular endowment in the developing chicken embryo lung. Am J Phys Lung Cell Mol Phys. 2007;292:L1136–46.

    CAS  Google Scholar 

  107. Kilarski WW, Samolov B, Petersson L, Kvanta A, Gerwins P. Biomechanical regulation of blood vessel growth during tissue vascularization. Nat Med. 2009;15:657–64.

    Article  CAS  PubMed  Google Scholar 

  108. Huang CC, Lawson ND, Weinstein BM, Johnson SL. reg6 is required for branching morphogenesis during blood vessel regeneration in zebrafish caudal fins. Dev Biol. 2003;264:263–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Fruttiger M. Development of the retinal vasculature. Angiogenesis. 2007;10:77–88.

    Article  PubMed  Google Scholar 

  110. Lenard A, Daetwyler S, Betz C, Ellertsdottir E, Belting HG, Huisken J, Affolter M. Endothelial cell self-fusion during vascular pruning. PLoS Biol. 2015;13:e1002126.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Mirabelli P, Peebo BB, Xeroudaki M, Koulikovska M, Lagali N. Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model. Exp Eye Res. 2014;125:118–27.

    Article  CAS  PubMed  Google Scholar 

  112. Mancuso MR, Davis R, Norberg SM, O’Brien S, Sennino B, Nakahara T, Yao VJ, Inai T, Brooks P, Freimark B, Shalinsky DR, Hu-Lowe DD, McDonald DM. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest. 2006;116:2610–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Noguera-Troise I, Daly C, Papadopoulos NJ, Coetzee S, Boland P, Gale NW, Lin HC, Yancopoulos GD, Thurston G. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature. 2006;444:1032–7.

    Article  CAS  PubMed  Google Scholar 

  114. Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 2011;91:1071–121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Larrivee B, Freitas C, Trombe M, Lv X, Delafarge B, Yuan L, Bouvree K, Breant C, Del Toro R, Brechot N, Germain S, Bono F, Dol F, Claes F, Fischer C, Autiero M, Thomas JL, Carmeliet P, Tessier-Lavigne M, Eichmann A. Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis. Genes Dev. 2007;21:2433–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Miloudi K, Binet F, Wilson A, Cerani A, Oubaha M, Menard C, Henriques S, Mawambo G, Dejda A, Nguyen PT, Rezende FA, Bourgault S, Kennedy TE, Sapieha P. Truncated netrin-1 contributes to pathological vascular permeability in diabetic retinopathy. J Clin Invest. 2016;126:3006–22.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Neufeld G, Sabag AD, Rabinovicz N, Kessler O. Semaphorins in angiogenesis and tumor progression. Cold Spring Harb Perspect Med. 2012;2:a006718.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Alders M, Hogan BM, Gjini E, Salehi F, Al-Gazali L, Hennekam EA, Holmberg EE, Mannens MM, Mulder MF, Offerhaus GJ, Prescott TE, Schroor EJ, Verheij JB, Witte M, Zwijnenburg PJ, Vikkula M, Schulte-Merker S, Hennekam RC. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nat Genet. 2009;41:1272–4.

    Article  CAS  PubMed  Google Scholar 

  119. Munn LL. Mechanobiology of lymphatic contractions. Semin Cell Dev Biol. 2015;38:67–74.

    Article  CAS  PubMed  Google Scholar 

  120. Betterman KL, Paquet-Fifield S, Asselin-Labat ML, Visvader JE, Butler LM, Stacker SA, Achen MG, Harvey NL. Remodeling of the lymphatic vasculature during mouse mammary gland morphogenesis is mediated via epithelial-derived lymphangiogenic stimuli. Am J Pathol. 2012;181:2225–38.

    Article  CAS  PubMed  Google Scholar 

  121. Sironi M, Conti A, Bernasconi S, Fra AM, Pasqualini F, Nebuloni M, Lauri E, De Bortoli M, Mantovani A, Dejana E, Vecchi A. Generation and characterization of a mouse lymphatic endothelial cell line. Cell Tissue Res. 2006;325:91–100.

    Article  PubMed  Google Scholar 

  122. Wigle JT, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn MD, Jackson DG, Oliver G. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 2002;21:1505–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol. 2007;8:464–78.

    Article  CAS  PubMed  Google Scholar 

  124. Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova TV, Jeltsch M, Jackson DG, Talikka M, Rauvala H, Betsholtz C, Alitalo K. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol. 2004;5:74–80.

    Article  CAS  PubMed  Google Scholar 

  125. Okuda KS, Astin JW, Misa JP, Flores MV, Crosier KE, Crosier PS. lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic vessel development in zebrafish. Development. 2012;139:2381–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Yang S, Zhao J, Sun X. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des Devel Ther. 2016;10:1857–67.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Yang Y, Bailey C, Holz FG, Eter N, Weber M, Baker C, Kiss S, Menchini U, Ruiz Moreno JM, Dugel P, Lotery A, FAME study group. Long-term outcomes of phakic patients with diabetic macular oedema treated with intravitreal fluocinolone acetonide (FAc) implants. Eye (Lond). 2015;29:1173–80.

    Article  CAS  Google Scholar 

  128. Cao Y. Antiangiogenic cancer therapy: why do mouse and human patients respond in a different way to the same drug? Int J Dev Biol. 2011;55:557–62.

    Article  CAS  PubMed  Google Scholar 

  129. Cao Y. Therapeutic angiogenesis for ischemic disorders: what is missing for clinical benefits? Discov Med. 2010;9:179–84.

    PubMed  Google Scholar 

  130. Henri O, Pouehe C, Houssari M, Galas L, Nicol L, Edwards-Levy F, Henry JP, Dumesnil A, Boukhalfa I, Banquet S, Schapman D, Thuillez C, Richard V, Mulder P, Brakenhielm E. Selective stimulation of cardiac lymphangiogenesis reduces myocardial edema and fibrosis leading to improved cardiac function following myocardial infarction. Circulation. 2016;133:1484–97; discussion 1497.

    Google Scholar 

  131. Jensen LD, Gyllenhaal C, Block K. Circadian angiogenesis. Biomol Concepts. 2014;5:245–56.

    Article  CAS  PubMed  Google Scholar 

  132. Jensen LD, Cao Z, Nakamura M, Yang Y, Brautigam L, Andersson P, Zhang Y, Wahlberg E, Lanne T, Hosaka K, Cao Y. Opposing effects of circadian clock genes bmal1 and period2 in regulation of VEGF-dependent angiogenesis in developing zebrafish. Cell Rep. 2012;2:231–41.

    Article  CAS  PubMed  Google Scholar 

  133. Cruys B, Wong BW, Kuchnio A, Verdegem D, Cantelmo AR, Conradi LC, Vandekeere S, Bouche A, Cornelissen I, Vinckier S, Merks RM, Dejana E, Gerhardt H, Dewerchin M, Bentley K, Carmeliet P. Glycolytic regulation of cell rearrangement in angiogenesis. Nat Commun. 2016;7:12240.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical and Health Sciences, Linköping University, Campus US, Ingång 68, Pl. 08, SE-58185, Linköping, Sweden

    L. Jensen

  2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-17177, Stockholm, Sweden

    L. Jensen & Y. Cao

  3. Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, LE3 9QP, UK

    Y. Cao

Authors
  1. L. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Jensen .

Editor information

Editors and Affiliations

  1. Emory University School of Medicine, Atlanta, Georgia, USA

    Jack L. Arbiser

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer-Verlag London Ltd.

About this chapter

Cite this chapter

Jensen, L., Cao, Y. (2017). Angiogenesis: General Concepts. In: Arbiser, J. (eds) Angiogenesis-Based Dermatology. Springer, London. https://doi.org/10.1007/978-1-4471-7314-4_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-7314-4_1

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-7312-0

  • Online ISBN: 978-1-4471-7314-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation