Endothelial Cell Origin, Differentiation, Heterogeneity and Function

  • Anna Grochot-Przęczek
  • Magdalena Kozakowska
  • Józef Dulak
  • Alicja JózkowiczEmail author


The endothelium forms a cellular lining of blood vessels in the circulatory system, but its function goes far beyond the creation of a structural barrier between blood and tissues. It is a multifunctional, complex organ, engaged in numerous physiological and pathological processes. This chapter focuses on several basic aspects related to endothelium and tries to answer the following questions: what is the precursor of endothelial cell, how the endothelial cell gains venous, arterial or lymphatic fate, what are the main mechanisms responsible for blood vessel formation and finally, is there any variety in structure and function of endothelium throughout the vascular system?


Endothelium Hemangioblast Endothelial cell differentiation Angiogenesis 



The Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University is a beneficiary of the structural funds from the European Union and the Polish Ministry of Science and Higher Education (grants no: POIG.02.01.00-12 064/08, POIG 01.01.02-00-109/09, POIG.02.02.00-014/08 and 01.01.02-00-069/09).


  1. 1.
    Fishman AP (1982) Endothelium: a distributed organ of diverse capabilities. Ann N Y Acad Sci 401:1–8PubMedGoogle Scholar
  2. 2.
    Aird WC (2007) Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res 100(2):158–173PubMedGoogle Scholar
  3. 3.
    DeWitt N (2005) Angiogenesis. Nature 438(931)Google Scholar
  4. 4.
    Augustin HG, Kozian DH, Johnson RC (1994) Differentiation of endothelial cells: analysis of the constitutive and activated endothelial cell phenotypes. Bioessays 16(12):901–906PubMedGoogle Scholar
  5. 5.
    McGrath KE, Koniski AD, Malik J, Palis J (2003) Circulation is established in a stepwise pattern in the mammalian embryo. Blood 101(5):1669–1676PubMedGoogle Scholar
  6. 6.
    Risau W, Sariola H, Zerwes HG, Sasse J, Ekblom P, Kemler R, Doetschman T (1988) Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development 102(3):471–478PubMedGoogle Scholar
  7. 7.
    Weinstein BM (1999) What guides early embryonic blood vessel formation? Dev Dyn 215(1):2–11PubMedGoogle Scholar
  8. 8.
    Cox CM, Poole TJ (2000) Angioblast differentiation is influenced by the local environment: FGF-2 induces angioblasts and patterns vessel formation in the quail embryo. Dev Dyn 218(2):371–382PubMedGoogle Scholar
  9. 9.
    Pardanaud L, Dieterlen-Lievre F (1999) Manipulation of the angiopoietic/hemangiopoietic commitment in the avian embryo. Development 126(4):617–627PubMedGoogle Scholar
  10. 10.
    Leconte I, Fox JC, Baldwin HS, Buck CA, Swain JL (1998) Adenoviral-mediated expression of antisense RNA to fibroblast growth factors disrupts murine vascular development. Dev Dyn 213(4):421–430PubMedGoogle Scholar
  11. 11.
    Lee SH, Schloss DJ, Swain JL (2000) Maintenance of vascular integrity in the embryo requires signaling through the fibroblast growth factor receptor. J Biol Chem 275(43):33679–33687PubMedGoogle Scholar
  12. 12.
    Kanno S, Oda N, Abe M, Terai Y, Ito M, Shitara K, Tabayashi K, Shibuya M, Sato Y (2000) Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial cells. Oncogene 19(17):2138–2146PubMedGoogle Scholar
  13. 13.
    Millauer B, Wizigmann-Voos S, Schnurch H, Martinez R, Moller NP, Risau W, Ullrich A (1993) High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72(6):835–846PubMedGoogle Scholar
  14. 14.
    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 (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573):435–439PubMedGoogle Scholar
  15. 15.
    Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573):439–442PubMedGoogle Scholar
  16. 16.
    Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376(6535):62–66PubMedGoogle Scholar
  17. 17.
    Kearney JB, Ambler CA, Monaco KA, Johnson N, Rapoport RG, Bautch VL (2002) Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division. Blood 99(7):2397–2407PubMedGoogle Scholar
  18. 18.
    Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87(7):1171–1180PubMedGoogle Scholar
  19. 19.
    Vikkula M, Boon LM, Carraway KL III, Calvert JT, Diamonti AJ, Goumnerov B, Pasyk KA, Marchuk DA, Warman ML, Cantley LC, Mulliken JB, Olsen BR (1996) Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell 87(7):1181–1190PubMedGoogle Scholar
  20. 20.
    Sabin FR (1920) Studies on the origin of blood vessels and of red corpuscules as seen in the living blastoderm of the chick during the second day of incubation: contributions to embryology. Contrib Embryol 9:213–262Google Scholar
  21. 21.
    Murray PDF (1932) The development in vitro of the blood of the early chick embryo. Proc R Soc Lond 11:497–521Google Scholar
  22. 22.
    Hirschi KK (2012) Hemogenic endothelium during development and beyond. Blood 119(21):4823–4827PubMedGoogle Scholar
  23. 23.
    Kennedy M, Firpo M, Choi K, Wall C, Robertson S, Kabrun N, Keller G (1997) A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386(6624):488–493PubMedGoogle Scholar
  24. 24.
    Choi K, Kennedy M, Kazarov A, Papadimitriou JC, Keller G (1998) A common precursor for hematopoietic and endothelial cells. Development 125(4):725–732PubMedGoogle Scholar
  25. 25.
    Nishikawa SI, Nishikawa S, Hirashima M, Matsuyoshi N, Kodama H (1998) Progressive lineage analysis by cell sorting and culture identifies FLK1 + VE-cadherin + cells at a diverging point of endothelial and hemopoietic lineages. Development 125(9):1747–1757PubMedGoogle Scholar
  26. 26.
    Huber TL, Kouskoff V, Fehling HJ, Palis J, Keller G (2004) Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature 432(7017):625–630PubMedGoogle Scholar
  27. 27.
    Vogeli KM, Jin SW, Martin GR, Stainier DY (2006) A common progenitor for haematopoietic and endothelial lineages in the zebrafish gastrula. Nature 443(7109):337–339PubMedGoogle Scholar
  28. 28.
    Kinder SJ, Tsang TE, Quinlan GA, Hadjantonakis AK, Nagy A, Tam PP (1999) The orderly allocation of mesodermal cells to the extraembryonic structures and the anteroposterior axis during gastrulation of the mouse embryo. Development 126(21):4691–4701PubMedGoogle Scholar
  29. 29.
    Furuta C, Ema H, Takayanagi S, Ogaeri T, Okamura D, Matsui Y, Nakauchi H (2006) Discordant developmental waves of angioblasts and hemangioblasts in the early gastrulating mouse embryo. Development 133(14):2771–2779PubMedGoogle Scholar
  30. 30.
    Fehling HJ, Lacaud G, Kubo A, Kennedy M, Robertson S, Keller G, Kouskoff V (2003) Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation. Development 130(17):4217–4227PubMedGoogle Scholar
  31. 31.
    Motoike T, Markham DW, Rossant J, Sato TN (2003) Evidence for novel fate of Flk1+ progenitor: contribution to muscle lineage. Genesis 35(3):153–159PubMedGoogle Scholar
  32. 32.
    Eichmann A, Corbel C, Nataf V, Vaigot P, Breant C, Le Douarin NM (1997) Ligand-dependent development of the endothelial and hemopoietic lineages from embryonic mesodermal cells expressing vascular endothelial growth factor receptor 2. Proc Natl Acad Sci U S A 94(10):5141–5146PubMedCentralPubMedGoogle Scholar
  33. 33.
    Wu Y, Moser M, Bautch VL, Patterson C (2003) HoxB5 is an upstream transcriptional switch for differentiation of the vascular endothelium from precursor cells. Mol Cell Biol 23(16):5680–5691PubMedCentralPubMedGoogle Scholar
  34. 34.
    Park C, Afrikanova I, Chung YS, Zhang WJ, Arentson E, Fong Gh G, Rosendahl A, Choi K (2004) A hierarchical order of factors in the generation of FLK1- and SCL-expressing hematopoietic and endothelial progenitors from embryonic stem cells. Development 131(11):2749–2762PubMedGoogle Scholar
  35. 35.
    Lugus JJ, Chung YS, Mills JC, Kim SI, Grass J, Kyba M, Doherty JM, Bresnick EH, Choi K (2007) GATA2 functions at multiple steps in hemangioblast development and differentiation. Development 134(2):393–405PubMedGoogle Scholar
  36. 36.
    Pelosi E, Valtieri M, Coppola S, Botta R, Gabbianelli M, Lulli V, Marziali G, Masella B, Muller R, Sgadari C, Testa U, Bonanno G, Peschle C (2002) Identification of the hemangioblast in postnatal life. Blood 100(9):3203–3208PubMedGoogle Scholar
  37. 37.
    Gunsilius E, Duba HC, Petzer AL, Kahler CM, Grunewald K, Stockhammer G, Gabl C, Dirnhofer S, Clausen J, Gastl G (2000) Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells. Lancet 355(9216):1688–1691PubMedGoogle Scholar
  38. 38.
    Lugus JJ, Park C, Ma YD, Choi K (2009) Both primitive and definitive blood cells are derived from Flk-1+ mesoderm. Blood 113(3):563–566PubMedGoogle Scholar
  39. 39.
    de Bruijn MF, Speck NA, Peeters MC, Dzierzak E (2000) Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo. EMBO J 19(11):2465–2474PubMedGoogle Scholar
  40. 40.
    Tavian M, Coulombel L, Luton D, Clemente HS, Dieterlen-Lievre F, Peault B (1996) Aorta-associated CD34+ hematopoietic cells in the early human embryo. Blood 87(1):67–72PubMedGoogle Scholar
  41. 41.
    Marshall CJ, Thrasher AJ (2001) The embryonic origins of human haematopoiesis. Br J Haematol 112(4):838–850PubMedGoogle Scholar
  42. 42.
    Tavian M, Cortes F, Charbord P, Labastie MC, Peault B (1999) Emergence of the haematopoietic system in the human embryo and foetus. Haematologica 84(Suppl EHA-4):1–3PubMedGoogle Scholar
  43. 43.
    Jaffredo T, Gautier R, Eichmann A, Dieterlen-Lievre F (1998) Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny. Development 125(22):4575–4583PubMedGoogle Scholar
  44. 44.
    Lancrin C, Sroczynska P, Stephenson C, Allen T, Kouskoff V, Lacaud G (2009) The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage. Nature 457(7231):892–895PubMedCentralPubMedGoogle Scholar
  45. 45.
    Oberlin E, Tavian M, Blazsek I, Peault B (2002) Blood-forming potential of vascular endothelium in the human embryo. Development 129(17):4147–4157PubMedGoogle Scholar
  46. 46.
    Eilken HM, Nishikawa S, Schroeder T (2009) Continuous single-cell imaging of blood generation from haemogenic endothelium. Nature 457(7231):896–900PubMedGoogle Scholar
  47. 47.
    Chen MJ, Yokomizo T, Zeigler BM, Dzierzak E, Speck NA (2009) Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature 457(7231):887–891PubMedCentralPubMedGoogle Scholar
  48. 48.
    Zovein AC, Hofmann JJ, Lynch M, French WJ, Turlo KA, Yang Y, Becker MS, Zanetta L, Dejana E, Gasson JC, Tallquist MD, Iruela-Arispe ML (2008) Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 3(6):625–636PubMedCentralPubMedGoogle Scholar
  49. 49.
    Sroczynska P, Lancrin C, Kouskoff V, Lacaud G (2009) The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis. Blood 114(26):5279–5289PubMedGoogle Scholar
  50. 50.
    Yokomizo T, Ogawa M, Osato M, Kanno T, Yoshida H, Fujimoto T, Fraser S, Nishikawa S, Okada H, Satake M, Noda T, Ito Y (2001) Requirement of Runx1/AML1/PEBP2alphaB for the generation of haematopoietic cells from endothelial cells. Genes Cells 6(1):13–23PubMedGoogle Scholar
  51. 51.
    Mukouyama Y, Chiba N, Hara T, Okada H, Ito Y, Kanamaru R, Miyajima A, Satake M, Watanabe T (2000) The AML1 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic aorta-gonad-mesonephros region. Dev Biol 220(1):27–36PubMedGoogle Scholar
  52. 52.
    North TE, de Bruijn MF, Stacy T, Talebian L, Lind E, Robin C, Binder M, Dzierzak E, Speck NA (2002) Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity 16(5):661–672PubMedGoogle Scholar
  53. 53.
    Nadin BM, Goodell MA, Hirschi KK (2003) Phenotype and hematopoietic potential of side population cells throughout embryonic development. Blood 102(7):2436–2443PubMedGoogle Scholar
  54. 54.
    Goldie LC, Lucitti JL, Dickinson ME, Hirschi KK (2008) Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis. Blood 112(8):3194–3204PubMedGoogle Scholar
  55. 55.
    Pearson JD (2010) Endothelial progenitor cells—an evolving story. Microvasc Res 79(3):162–168PubMedGoogle Scholar
  56. 56.
    Grochot-Przeczek A, Dulak J, Jozkowicz A (2013) Therapeutic angiogenesis for revascularization in peripheral artery disease. Gene 525(2):220–228PubMedGoogle Scholar
  57. 57.
    Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967PubMedGoogle Scholar
  58. 58.
    Stump MM, Jordan GL Jr, Debakey ME, Halpert B (1963) Endothelium grown from circulating blood on isolated intravascular Dacron hub. Am J Pathol 43:361–367PubMedGoogle Scholar
  59. 59.
    Shi Q, Wu MH, Hayashida N, Wechezak AR, Clowes AW, Sauvage LR (1994) Proof of fallout endothelialization of impervious Dacron grafts in the aorta and inferior vena cava of the dog. J Vasc Surg 20(4):546–556, discussion 556–547PubMedGoogle Scholar
  60. 60.
    Shi Q, Rafii S, Wu MH, Wijelath ES, Yu C, Ishida A, Fujita Y, Kothari S, Mohle R, Sauvage LR, Moore MA, Storb RF, Hammond WP (1998) Evidence for circulating bone marrow-derived endothelial cells. Blood 92(2):362–367PubMedGoogle Scholar
  61. 61.
    Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85(3):221–228PubMedGoogle Scholar
  62. 62.
    Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18(14):3964–3972PubMedGoogle Scholar
  63. 63.
    Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T (1999) Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5(4):434–438PubMedGoogle Scholar
  64. 64.
    Pearson JD (2009) Endothelial progenitor cells – hype or hope? J Thromb Haemost 7(2):255–262PubMedGoogle Scholar
  65. 65.
    Loomans CJ, Wan H, de Crom R, van Haperen R, de Boer HC, Leenen PJ, Drexhage HA, Rabelink TJ, van Zonneveld AJ, Staal FJ (2006) Angiogenic murine endothelial progenitor cells are derived from a myeloid bone marrow fraction and can be identified by endothelial NO synthase expression. Arterioscler Thromb Vasc Biol 26(8):1760–1767PubMedGoogle Scholar
  66. 66.
    Hristov M, Erl W, Weber PC (2003) Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol 23(7):1185–1189PubMedGoogle Scholar
  67. 67.
    Hur J, Yoon CH, Kim HS, Choi JH, Kang HJ, Hwang KK, Oh BH, Lee MM, Park YB (2004) Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol 24(2):288–293PubMedGoogle Scholar
  68. 68.
    Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, Li F, Krasich R, Temm CJ, Prchal JT, Ingram DA (2007) Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 109(5):1801–1809PubMedGoogle Scholar
  69. 69.
    Rohde E, Malischnik C, Thaler D, Maierhofer T, Linkesch W, Lanzer G, Guelly C, Strunk D (2006) Blood monocytes mimic endothelial progenitor cells. Stem Cells 24(2):357–367PubMedGoogle Scholar
  70. 70.
    Kim SJ, Kim JS, Papadopoulos J, Wook Kim S, Maya M, Zhang F, He J, Fan D, Langley R, Fidler IJ (2009) Circulating monocytes expressing CD31: implications for acute and chronic angiogenesis. Am J Pathol 174(5):1972–1980PubMedGoogle Scholar
  71. 71.
    Prokopi M, Pula G, Mayr U, Devue C, Gallagher J, Xiao Q, Boulanger CM, Westwood N, Urbich C, Willeit J, Steiner M, Breuss J, Xu Q, Kiechl S, Mayr M (2009) Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures. Blood 114(3):723–732PubMedGoogle Scholar
  72. 72.
    Raemer PC, Haemmerling S, Giese T, Canaday DH, Katus HA, Dengler TJ, Sivanandam VG (2009) Endothelial progenitor cells possess monocyte-like antigen-presenting and T-cell-co-stimulatory capacity. Transplantation 87(3):340–349PubMedGoogle Scholar
  73. 73.
    Harvey W (1957) Movement of the heart and blood in animals: an anatomical essay. Blackwell Scientific, Oxford, UKGoogle Scholar
  74. 74.
    Lawson ND, Weinstein BM (2002) Arteries and veins: making a difference with zebrafish. Nat Rev Genet 3(9):674–682PubMedGoogle Scholar
  75. 75.
    Thompson MA, Ransom DG, Pratt SJ, MacLennan H, Kieran MW, Detrich HW III, Vail B, Huber TL, Paw B, Brownlie AJ, Oates AC, Fritz A, Gates MA, Amores A, Bahary N, Talbot WS, Her H, Beier DR, Postlethwait JH, Zon LI (1998) The cloche and spadetail genes differentially affect hematopoiesis and vasculogenesis. Dev Biol 197(2):248–269PubMedGoogle Scholar
  76. 76.
    You LR, Lin FJ, Lee CT, DeMayo FJ, Tsai MJ, Tsai SY (2005) Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature 435(7038):98–104PubMedGoogle Scholar
  77. 77.
    Odenthal J, Haffter P, Vogelsang E, Brand M, van Eeden FJ, Furutani-Seiki M, Granato M, Hammerschmidt M, Heisenberg CP, Jiang YJ, Kane DA, Kelsh RN, Mullins MC, Warga RM, Allende ML, Weinberg ES, Nusslein-Volhard C (1996) Mutations affecting the formation of the notochord in the zebrafish, Danio rerio. Development 123:103–115PubMedGoogle Scholar
  78. 78.
    Fan CM, Tessier-Lavigne M (1994) Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog. Cell 79(7):1175–1186PubMedGoogle Scholar
  79. 79.
    Ericson J, Morton S, Kawakami A, Roelink H, Jessell TM (1996) Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Cell 87(4):661–673PubMedGoogle Scholar
  80. 80.
    Schauerte HE, van Eeden FJ, Fricke C, Odenthal J, Strahle U, Haffter P (1998) Sonic hedgehog is not required for the induction of medial floor plate cells in the zebrafish. Development 125(15):2983–2993PubMedGoogle Scholar
  81. 81.
    Lawson ND, Vogel AM, Weinstein BM (2002) sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation. Dev Cell 3(1):127–136PubMedGoogle Scholar
  82. 82.
    Lawson ND, Scheer N, Pham VN, Kim CH, Chitnis AB, Campos-Ortega JA, Weinstein BM (2001) Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development 128(19):3675–3683PubMedGoogle Scholar
  83. 83.
    Zhong TP, Childs S, Leu JP, Fishman MC (2001) Gridlock signalling pathway fashions the first embryonic artery. Nature 414(6860):216–220PubMedGoogle Scholar
  84. 84.
    Moyon D, Pardanaud L, Yuan L, Breant C, Eichmann A (2001) Plasticity of endothelial cells during arterial-venous differentiation in the avian embryo. Development 128(17):3359–3370PubMedGoogle Scholar
  85. 85.
    Albrecht I, Christofori G (2011) Molecular mechanisms of lymphangiogenesis in development and cancer. Int J Dev Biol 55(4–5):483–494PubMedGoogle Scholar
  86. 86.
    Potente M, Gerhardt H, Carmeliet P (2011) Basic and therapeutic aspects of angiogenesis. Cell 146(6):873–887PubMedGoogle Scholar
  87. 87.
    Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev 6(4):273–286Google Scholar
  88. 88.
    Fagiani E, Christofori G (2013) Angiopoietins in angiogenesis. Cancer Lett 328(1):18–26PubMedGoogle Scholar
  89. 89.
    Rey S, Semenza GL (2010) Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling. Cardiovasc Res 86(2):236–242PubMedGoogle Scholar
  90. 90.
    Semenza GL (2007) Vasculogenesis, angiogenesis, and arteriogenesis: mechanisms of blood vessel formation and remodeling. J Cell Biochem 102(4):840–847PubMedGoogle Scholar
  91. 91.
    Al Haj Zen A, Madeddu P (2009) Notch signalling in ischaemia-induced angiogenesis. Biochem Soc Trans 37(Pt 6):1221–1227PubMedCentralPubMedGoogle Scholar
  92. 92.
    Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM (1998) Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91(10):3527–3561PubMedGoogle Scholar
  93. 93.
    Ferrara N (2009) VEGF-A: a critical regulator of blood vessel growth. Eur Cytokine Netw 20(4):158–163PubMedGoogle Scholar
  94. 94.
    Jakobsson L, Bentley K, Gerhardt H (2009) VEGFRs and Notch: a dynamic collaboration in vascular patterning. Biochem Soc Trans 37(Pt 6):1233–1236PubMedGoogle Scholar
  95. 95.
    Ucuzian AA, Gassman AA, East AT, Greisler HP (2010) Molecular mediators of angiogenesis. J Burn Care Res 31(1):158–175PubMedCentralPubMedGoogle Scholar
  96. 96.
    Davis GE, Senger DR (2008) Extracellular matrix mediates a molecular balance between vascular morphogenesis and regression. Curr Opin Hematol 15(3):197–203PubMedGoogle Scholar
  97. 97.
    Lamalice L, Le Boeuf F, Huot J (2007) Endothelial cell migration during angiogenesis. Circ Res 100(6):782–794PubMedGoogle Scholar
  98. 98.
    Davis GE, Stratman AN, Sacharidou A, Koh W (2011) Molecular basis for endothelial lumen formation and tubulogenesis during vasculogenesis and angiogenic sprouting. Int Rev Cell Mol Biol 288:101–165PubMedCentralPubMedGoogle Scholar
  99. 99.
    Domigan CK, Iruela-Arispe ML (2012) Recent advances in vascular development. Curr Opin Hematol 19(3):176–183PubMedCentralPubMedGoogle Scholar
  100. 100.
    Ribatti D, Nico B, Crivellato E (2011) The role of pericytes in angiogenesis. Int J Dev Biol 55(3):261–268PubMedGoogle Scholar
  101. 101.
    Aird WC (2007) Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ Res 100(2):174–190PubMedGoogle Scholar
  102. 102.
    Aird WC (2012) Endothelial cell heterogeneity. Cold Spring Harb Perspect Med 2(1):a006429PubMedGoogle Scholar
  103. 103.
    Sumpio BE, Riley JT, Dardik A (2002) Cells in focus: endothelial cell. Int J Biochem Cell Biol 34(12):1508–1512PubMedGoogle Scholar
  104. 104.
    Ordonez NG (2012) Immunohistochemical endothelial markers: a review. Adv Anat Pathol 19(5):281–295PubMedGoogle Scholar
  105. 105.
    Aird WC (2008) Endothelium in health and disease. Pharmacol Rep 60(1):139–143PubMedGoogle Scholar
  106. 106.
    Tse D, Stan RV (2010) Morphological heterogeneity of endothelium. Semin Thromb Hemost 36(3):236–245PubMedGoogle Scholar
  107. 107.
    Chavez A, Smith M, Mehta D (2011) New insights into the regulation of vascular permeability. Int Rev Cell Mol Biol 290:205–248PubMedGoogle Scholar
  108. 108.
    Dyer LA, Patterson C (2010) Development of the endothelium: an emphasis on heterogeneity. Semin Thromb Hemost 36(3):227–235PubMedCentralPubMedGoogle Scholar
  109. 109.
    Davies PF, Civelek M, Fang Y, Guerraty MA, Passerini AG (2010) Endothelial heterogeneity associated with regional athero-susceptibility and adaptation to disturbed blood flow in vivo. Semin Thromb Hemost 36(3):265–275PubMedGoogle Scholar
  110. 110.
    dela Paz NG, D’Amore PA (2009) Arterial versus venous endothelial cells. Cell Tissue Res 335(1):5–16PubMedGoogle Scholar
  111. 111.
    Triggle CR, Samuel SM, Ravishankar S, Marei I, Arunachalam G, Ding H (2012) The endothelium: influencing vascular smooth muscle in many ways. Can J Physiol Pharmacol 90(6):713–738PubMedGoogle Scholar
  112. 112.
    van Hinsbergh VW (2011) Endothelium – role in regulation of coagulation and inflammation. Semin Immunopathol 34(1):93–106PubMedCentralPubMedGoogle Scholar
  113. 113.
    Lee S, Choi I, Hong YK (2010) Heterogeneity and plasticity of lymphatic endothelial cells. Semin Thromb Hemost 36(3):352–361PubMedCentralPubMedGoogle Scholar
  114. 114.
    Kume T (2010) Specification of arterial, venous, and lymphatic endothelial cells during embryonic development. Histol Histopathol 25(5):637–646PubMedCentralPubMedGoogle Scholar
  115. 115.
    Quadri SK (2012) Cross talk between focal adhesion kinase and cadherins: role in regulating endothelial barrier function. Microvasc Res 83(1):3–11PubMedCentralPubMedGoogle Scholar
  116. 116.
    Curry FE, Adamson RH (2012) Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng 40(4):828–839PubMedGoogle Scholar
  117. 117.
    Bates DO (2010) Vascular endothelial growth factors and vascular permeability. Cardiovasc Res 87(2):262–271PubMedGoogle Scholar
  118. 118.
    Young MR (2012) Endothelial cells in the eyes of an immunologist. Cancer Immunol Immunother 61(10):1609–1616PubMedCentralPubMedGoogle Scholar
  119. 119.
    Williams MR, Azcutia V, Newton G, Alcaide P, Luscinskas FW (2011) Emerging mechanisms of neutrophil recruitment across endothelium. Trends Immunol 32(10):461–469PubMedCentralPubMedGoogle Scholar
  120. 120.
    Molema G (2010) Heterogeneity in endothelial responsiveness to cytokines, molecular causes, and pharmacological consequences. Semin Thromb Hemost 36(3):246–264PubMedGoogle Scholar
  121. 121.
    Barton M (2011) The discovery of endothelium-dependent contraction: the legacy of Paul M. Vanhoutte. Pharmacol Res 63(6):455–462PubMedGoogle Scholar
  122. 122.
    Schwartz BG, Economides C, Mayeda GS, Burstein S, Kloner RA (2010) The endothelial cell in health and disease: its function, dysfunction, measurement and therapy. Int J Impot Res 22(2):77–90PubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Anna Grochot-Przęczek
    • 1
    • 2
  • Magdalena Kozakowska
    • 1
    • 2
  • Józef Dulak
    • 1
  • Alicja Józkowicz
    • 1
    Email author
  1. 1.Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and BiotechnologyJagiellonian UniversityKrakówPoland
  2. 2.Jagiellonian Centre for Experimental TherapeuticsJagiellonian UniversityKrakówPoland

Personalised recommendations