Cellular and Molecular Neurobiology

, Volume 31, Issue 2, pp 175–193 | Cite as

Brain Pericytes: Emerging Concepts and Functional Roles in Brain Homeostasis

  • Masahiro Kamouchi
  • Tetsuro Ago
  • Takanari Kitazono
Review Paper


Brain pericytes are an important constituent of neurovascular unit. They encircle endothelial cells and contribute to the maturation and stabilization of the capillaries in the brain. Recent studies have revealed that brain pericytes play pivotal roles in a variety of brain functions, such as regulation of capillary flow, angiogenesis, blood brain barrier, immune responses, and hemostasis. In addition, brain pericytes are pluripotent and can differentiate into different lineages similar to mesenchymal stem cells. The brain pericytes are revisited as a key player to maintain brain function and repair brain damage.


Angiogenesis Blood brain barrier Mesenchymal stem cell Microvasculature Pericyte 



This study was partially supported by Coordination, Support and Training Program for Translational Research and Grant-in-Aid for Scientific Research (C 19590992, C 22590937) from The Japanese Ministry of Education, Culture, Sports, Science and Technology. We are grateful to Dr. Masanori Wakisaka for his helpful comments.

Conflict of interest



  1. Abraham S, Kogata N, Fassler R, Adams RH (2008) Integrin β1 subunit controls mural cell adhesion, spreading, and blood vessel wall stability. Circ Res 102:562–570PubMedCrossRefGoogle Scholar
  2. Abramsson A, Kurup S, Busse M, Yamada S, Lindblom P, Schallmeiner E, Stenzel D, Sauvaget D, Ledin J, Ringvall M, Landegren U, Kjellen L, Bondjers G, Li JP, Lindahl U, Spillmann D, Betsholtz C, Gerhardt H (2007) Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development. Genes Dev 21:316–331PubMedCrossRefGoogle Scholar
  3. Allende ML, Proia RL (2002) Sphingosine-1-phosphate receptors and the development of the vascular system. Biochim Biophys Acta 1582:222–227PubMedGoogle Scholar
  4. Allende ML, Yamashita T, Proia RL (2003) G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation. Blood 102:3665–3667PubMedCrossRefGoogle Scholar
  5. Allt G, Lawrenson JG (2001) Pericytes: cell biology and pathology. Cells Tissues Organs 169:1–11PubMedCrossRefGoogle Scholar
  6. Andrae J, Gallini R, Betsholtz C (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22:1276–1312PubMedCrossRefGoogle Scholar
  7. Antonelli-Orlidge A, Saunders KB, Smith SR, D’Amore PA (1989) An activated form of transforming growth factor β is produced by cocultures of endothelial cells and pericytes. Proc Natl Acad Sci USA 86:4544–4548PubMedCrossRefGoogle Scholar
  8. Armulik A, Abramsson A, Betsholtz C (2005) Endothelial/pericyte interactions. Circ Res 97:512–523PubMedCrossRefGoogle Scholar
  9. Augustin HG, Reiss Y (2003) EphB receptors and ephrinB ligands: regulators of vascular assembly and homeostasis. Cell Tissue Res 314:25–31PubMedCrossRefGoogle Scholar
  10. Bababeygy SR, Cheshier SH, Hou LC, Higgins DM, Weissman IL, Tse VC (2008) Hematopoietic stem cell-derived pericytic cells in brain tumor angio-architecture. Stem Cells Dev 17:11–18PubMedCrossRefGoogle Scholar
  11. Bagley RG, Honma N, Weber W, Boutin P, Rouleau C, Shankara S, Kataoka S, Ishida I, Roberts BL, Teicher BA (2008) Endosialin/TEM 1/CD248 is a pericyte marker of embryonic and tumor neovascularization. Microvasc Res 76:180–188PubMedCrossRefGoogle Scholar
  12. Balabanov R, Dore-Duffy P (1998) Role of the CNS microvascular pericyte in the blood-brain barrier. J Neurosci Res 53:637–644PubMedCrossRefGoogle Scholar
  13. Balabanov R, Beaumont T, Dore-Duffy P (1999) Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T-lymphocytes. J Neurosci Res 55:578–587PubMedCrossRefGoogle Scholar
  14. Ball SG, Shuttleworth CA, Kielty CM (2007) Mesenchymal stem cells and neovascularization: role of platelet-derived growth factor receptors. J Cell Mol Med 11:1012–1030PubMedCrossRefGoogle Scholar
  15. Bandopadhyay R, Orte C, Lawrenson JG, Reid AR, De Silva S, Allt G (2001) Contractile proteins in pericytes at the blood-brain and blood-retinal barriers. J Neurocytol 30:35–44PubMedCrossRefGoogle Scholar
  16. Beck L Jr, D’Amore PA (1997) Vascular development: cellular and molecular regulation. FASEB J 11:365–373PubMedGoogle Scholar
  17. Bendayan R, Ronaldson PT, Gingras D, Bendayan M (2006) In situ localization of P-glycoprotein (ABCB1) in human and rat brain. J Histochem Cytochem 54:1159–1167PubMedCrossRefGoogle Scholar
  18. Benjamin LE, Hemo I, Keshet E (1998) A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125:1591–1598PubMedGoogle Scholar
  19. Berezowski V, Landry C, Dehouck MP, Cecchelli R, Fenart L (2004) Contribution of glial cells and pericytes to the mRNA profiles of P-glycoprotein and multidrug resistance-associated proteins in an in vitro model of the blood-brain barrier. Brain Res 1018:1–9PubMedCrossRefGoogle Scholar
  20. Berger M, Bergers G, Arnold B, Hammerling GJ, Ganss R (2005) Regulator of G-protein signaling-5 induction in pericytes coincides with active vessel remodeling during neovascularization. Blood 105:1094–1101PubMedCrossRefGoogle Scholar
  21. Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 7:452–464PubMedCrossRefGoogle Scholar
  22. Bernacki J, Dobrowolska A, Nierwinska K, Malecki A (2008) Physiology and pharmacological role of the blood-brain barrier. Pharmacol Rep 60:600–622PubMedGoogle Scholar
  23. Bertolino P, Deckers M, Lebrin F, ten Dijke P (2005) Transforming growth factor-β signal transduction in angiogenesis and vascular disorders. Chest 128:585S–590SPubMedCrossRefGoogle Scholar
  24. Bexell D, Gunnarsson S, Tormin A, Darabi A, Gisselsson D, Roybon L, Scheding S, Bengzon J (2009) Bone marrow multipotent mesenchymal stroma cells act as pericyte-like migratory vehicles in experimental gliomas. Mol Ther 17:183–190PubMedCrossRefGoogle Scholar
  25. Boado RJ, Pardridge WM (1994) Differential expression of α-actin mRNA and immunoreactive protein in brain microvascular pericytes and smooth muscle cells. J Neurosci Res 39:430–435PubMedCrossRefGoogle Scholar
  26. Bondjers C, He L, Takemoto M, Norlin J, Asker N, Hellstrom M, Lindahl P, Betsholtz C (2006) Microarray analysis of blood microvessels from PDGF-B and PDGF-Rβ mutant mice identifies novel markers for brain pericytes. FASEB J 20:1703–1705PubMedCrossRefGoogle Scholar
  27. Brachvogel B, Moch H, Pausch F, Schlotzer-Schrehardt U, Hofmann C, Hallmann R, von der Mark K, Winkler T, Poschl E (2005) Perivascular cells expressing annexin A5 define a novel mesenchymal stem cell-like population with the capacity to differentiate into multiple mesenchymal lineages. Development 132:2657–2668PubMedCrossRefGoogle Scholar
  28. Brachvogel B, Pausch F, Farlie P, Gaipl U, Etich J, Zhou Z, Cameron T, von der Mark K, Bateman JF, Poschl E (2007) Isolated Anxa5+/Sca-1+ perivascular cells from mouse meningeal vasculature retain their perivascular phenotype in vitro and in vivo. Exp Cell Res 313:2730–2743PubMedCrossRefGoogle Scholar
  29. Braun A, Xu H, Hu F, Kocherlakota P, Siegel D, Chander P, Ungvari Z, Csiszar A, Nedergaard M, Ballabh P (2007) Paucity of pericytes in germinal matrix vasculature of premature infants. J Neurosci 27:12012–12024PubMedCrossRefGoogle Scholar
  30. Cai J, Kehoe O, Smith GM, Hykin P, Boulton ME (2008) The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. Invest Ophthalmol Vis Sci 49:2163–2171PubMedCrossRefGoogle Scholar
  31. Cao R, Brakenhielm E, Pawliuk R, Wariaro D, Post MJ, Wahlberg E, Leboulch P, Cao Y (2003) Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2. Nat Med 9:604–613PubMedCrossRefGoogle Scholar
  32. Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3:229–230PubMedCrossRefGoogle Scholar
  33. Caplan AI (2009) Why are MSCs therapeutic? New data: new insight. J Pathol 217:318–324PubMedCrossRefGoogle Scholar
  34. Cardoso FL, Brites D, Brito MA (2010) Looking at the blood-brain barrier: molecular anatomy and possible investigation approaches. Brain Res Rev 64:328–363PubMedCrossRefGoogle Scholar
  35. Carnevale E, Fogel E, Aplin AC, Gelati M, Howson KM, Zhu WH, Nicosia RF (2007) Regulation of postangiogenic neovessel survival by β1 and β3 integrins in collagen and fibrin matrices. J Vasc Res 44:40–50PubMedCrossRefGoogle Scholar
  36. Carvalho RL, Jonker L, Goumans MJ, Larsson J, Bouwman P, Karlsson S, Dijke PT, Arthur HM, Mummery CL (2004) Defective paracrine signalling by TGFβ in yolk sac vasculature of endoglin mutant mice: a paradigm for hereditary haemorrhagic telangiectasia. Development 131:6237–6247PubMedCrossRefGoogle Scholar
  37. Cecchelli R, Berezowski V, Lundquist S, Culot M, Renftel M, Dehouck MP, Fenart L (2007) Modelling of the blood-brain barrier in drug discovery and development. Nat Rev Drug Discov 6:650–661PubMedCrossRefGoogle Scholar
  38. Chae SS, Paik JH, Furneaux H, Hla T (2004) Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference. J Clin Invest 114:1082–1089PubMedGoogle Scholar
  39. Chakravarthy U, Gardiner TA, Anderson P, Archer DB, Trimble ER (1992) The effect of endothelin 1 on the retinal microvascular pericyte. Microvasc Res 43:241–254PubMedCrossRefGoogle Scholar
  40. Chantrain CF, Henriet P, Jodele S, Emonard H, Feron O, Courtoy PJ, DeClerck YA, Marbaix E (2006) Mechanisms of pericyte recruitment in tumour angiogenesis: a new role for metalloproteinases. Eur J Cancer 42:310–318PubMedCrossRefGoogle Scholar
  41. Cho H, Kozasa T, Bondjers C, Betsholtz C, Kehrl JH (2003) Pericyte-specific expression of RGS5: implications for PDGF and EDG receptor signaling during vascular maturation. FASEB J 17:440–442PubMedGoogle Scholar
  42. Christian S, Winkler R, Helfrich I, Boos AM, Besemfelder E, Schadendorf D, Augustin HG (2008) Endosialin (Tem1) is a marker of tumor-associated myofibroblasts and tumor vessel-associated mural cells. Am J Pathol 172:486–494PubMedCrossRefGoogle Scholar
  43. Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313PubMedCrossRefGoogle Scholar
  44. da Silva Meirelles L, Caplan AI, Nardi NB (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26:2287–2299PubMedCrossRefGoogle Scholar
  45. Darland DC, D’Amore PA (2001) TGF β is required for the formation of capillary-like structures in three-dimensional cocultures of 10T1/2 and endothelial cells. Angiogenesis 4:11–20PubMedCrossRefGoogle Scholar
  46. Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD (1996) Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 87:1161–1169PubMedCrossRefGoogle Scholar
  47. De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M, Naldini L (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8:211–226PubMedCrossRefGoogle Scholar
  48. Dejana E (2004) Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol 5:261–270PubMedCrossRefGoogle Scholar
  49. Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E, Sacchetti B, Perani L, Innocenzi A, Galvez BG, Messina G, Morosetti R, Li S, Belicchi M, Peretti G, Chamberlain JS, Wright WE, Torrente Y, Ferrari S, Bianco P, Cossu G (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 9:255–267PubMedCrossRefGoogle Scholar
  50. Dewever J, Frerart F, Bouzin C, Baudelet C, Ansiaux R, Sonveaux P, Gallez B, Dessy C, Feron O (2007) Caveolin-1 is critical for the maturation of tumor blood vessels through the regulation of both endothelial tube formation and mural cell recruitment. Am J Pathol 171:1619–1628PubMedCrossRefGoogle Scholar
  51. Ding R, Darland DC, Parmacek MS, D’Amore PA (2004) Endothelial-mesenchymal interactions in vitro reveal molecular mechanisms of smooth muscle/pericyte differentiation. Stem Cells Dev 13:509–520PubMedGoogle Scholar
  52. Dohgu S, Takata F, Yamauchi A, Nakagawa S, Egawa T, Naito M, Tsuruo T, Sawada Y, Niwa M, Kataoka Y (2005) Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-β production. Brain Res 1038:208–215PubMedCrossRefGoogle Scholar
  53. Dore-Duffy P (2008) Pericytes: pluripotent cells of the blood brain barrier. Curr Pharm Des 14:1581–1593PubMedCrossRefGoogle Scholar
  54. Dore-Duffy P, Katychev A, Wang X, Van Buren E (2006) CNS microvascular pericytes exhibit multipotential stem cell activity. J Cereb Blood Flow Metab 26:613–624PubMedCrossRefGoogle Scholar
  55. Dufraine J, Funahashi Y, Kitajewski J (2008) Notch signaling regulates tumor angiogenesis by diverse mechanisms. Oncogene 27:5132–5137PubMedCrossRefGoogle Scholar
  56. Dumont DJ, Yamaguchi TP, Conlon RA, Rossant J, Breitman ML (1992) tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors. Oncogene 7:1471–1480PubMedGoogle Scholar
  57. Edelman DA, Jiang Y, Tyburski J, Wilson RF, Steffes C (2006) Pericytes and their role in microvasculature homeostasis. J Surg Res 135:305–311PubMedCrossRefGoogle Scholar
  58. Enge M, Bjarnegard M, Gerhardt H, Gustafsson E, Kalen M, Asker N, Hammes HP, Shani M, Fassler R, Betsholtz C (2002) Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J 21:4307–4316PubMedCrossRefGoogle Scholar
  59. Erber R, Eichelsbacher U, Powajbo V, Korn T, Djonov V, Lin J, Hammes HP, Grobholz R, Ullrich A, Vajkoczy P (2006) EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. EMBO J 25:628–641PubMedCrossRefGoogle Scholar
  60. Farrington-Rock C, Crofts NJ, Doherty MJ, Ashton BA, Griffin-Jones C, Canfield AE (2004) Chondrogenic and adipogenic potential of microvascular pericytes. Circulation 110:2226–2232PubMedCrossRefGoogle Scholar
  61. Fernandez LA, Sanz-Rodriguez F, Blanco FJ, Bernabeu C, Botella LM (2006) Hereditary hemorrhagic telangiectasia, a vascular dysplasia affecting the TGF-β signaling pathway. Clin Med Res 4:66–78CrossRefGoogle Scholar
  62. Ferrari-Dileo G, Davis EB, Anderson DR (1996) Glaucoma, capillaries and pericytes. 3. Peptide hormone binding and influence on pericytes. Ophthalmologica 210:269–275PubMedCrossRefGoogle Scholar
  63. Fiedler U, Augustin HG (2006) Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol 27:552–558PubMedCrossRefGoogle Scholar
  64. Foo SS, Turner CJ, Adams S, Compagni A, Aubyn D, Kogata N, Lindblom P, Shani M, Zicha D, Adams RH (2006) Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly. Cell 124:161–173PubMedCrossRefGoogle Scholar
  65. Frank RN, Dutta S, Mancini MA (1987) Pericyte coverage is greater in the retinal than in the cerebral capillaries of the rat. Invest Ophthalmol Vis Sci 28:1086–1091PubMedGoogle Scholar
  66. Fukushi J, Makagiansar IT, Stallcup WB (2004) NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and α3β1 integrin. Mol Biol Cell 15:3580–3590PubMedCrossRefGoogle Scholar
  67. Gaengel K, Genove G, Armulik A, Betsholtz C (2009) Endothelial-mural cell signaling in vascular development and angiogenesis. Arterioscler Thromb Vasc Biol 29:630–638PubMedCrossRefGoogle Scholar
  68. Gale NW, Baluk P, Pan L, Kwan M, Holash J, DeChiara TM, McDonald DM, Yancopoulos GD (2001) Ephrin-B2 selectively marks arterial vessels and neovascularization sites in the adult, with expression in both endothelial and smooth-muscle cells. Dev Biol 230:151–160PubMedCrossRefGoogle Scholar
  69. Garmy-Susini B, Jin H, Zhu Y, Sung RJ, Hwang R, Varner J (2005) Integrin α4β1-VCAM-1-mediated adhesion between endothelial and mural cells is required for blood vessel maturation. J Clin Invest 115:1542–1551PubMedCrossRefGoogle Scholar
  70. Gerhardt H, Betsholtz C (2003) Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314:15–23PubMedCrossRefGoogle Scholar
  71. Gerhardt H, Wolburg H, Redies C (2000) N-cadherin mediates pericytic-endothelial interaction during brain angiogenesis in the chicken. Dev Dyn 218:472–479PubMedCrossRefGoogle Scholar
  72. Goumans MJ, Liu Z, ten Dijke P (2009) TGF-β signaling in vascular biology and dysfunction. Cell Res 19:116–127PubMedCrossRefGoogle Scholar
  73. Grazioli A, Alves CS, Konstantopoulos K, Yang JT (2006) Defective blood vessel development and pericyte/pvSMC distribution in α 4 integrin-deficient mouse embryos. Dev Biol 293:165–177PubMedCrossRefGoogle Scholar
  74. Greenberg JI, Shields DJ, Barillas SG, Acevedo LM, Murphy E, Huang J, Scheppke L, Stockmann C, Johnson RS, Angle N, Cheresh DA (2008) A role for VEGF as a negative regulator of pericyte function and vessel maturation. Nature 456:809–813PubMedCrossRefGoogle Scholar
  75. Gridley T (2007) Notch signaling in vascular development and physiology. Development 134:2709–2718PubMedCrossRefGoogle Scholar
  76. Guillemin GJ, Brew BJ (2004) Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukoc Biol 75:388–397PubMedCrossRefGoogle Scholar
  77. Hall AP (2006) Review of the pericyte during angiogenesis and its role in cancer and diabetic retinopathy. Toxicol Pathol 34:763–775PubMedCrossRefGoogle Scholar
  78. Hammes HP, Lin J, Wagner P, Feng Y, Vom Hagen F, Krzizok T, Renner O, Breier G, Brownlee M, Deutsch U (2004) Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy. Diabetes 53:1104–1110PubMedCrossRefGoogle Scholar
  79. Hamzah J, Jugold M, Kiessling F, Rigby P, Manzur M, Marti HH, Rabie T, Kaden S, Grone HJ, Hammerling GJ, Arnold B, Ganss R (2008) Vascular normalization in RGS5-deficient tumours promotes immune destruction. Nature 453:410–414PubMedCrossRefGoogle Scholar
  80. Hartmann C, Zozulya A, Wegener J, Galla HJ (2007) The impact of glia-derived extracellular matrices on the barrier function of cerebral endothelial cells: an in vitro study. Exp Cell Res 313:1318–1325PubMedCrossRefGoogle Scholar
  81. Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57:173–185PubMedCrossRefGoogle Scholar
  82. Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C (1999) Role of PDGF-B and PDGFR-β in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126:3047–3055PubMedGoogle Scholar
  83. Hellstrom M, Gerhardt H, Kalen M, Li X, Eriksson U, Wolburg H, Betsholtz C (2001) Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol 153:543–553PubMedCrossRefGoogle Scholar
  84. Hirase H, Creso J, Singleton M, Bartho P, Buzsaki G (2004) Two-photon imaging of brain pericytes in vivo using dextran-conjugated dyes. Glia 46:95–100PubMedCrossRefGoogle Scholar
  85. Hirschi KK, D’Amore PA (1996) Pericytes in the microvasculature. Cardiovasc Res 32:687–698PubMedGoogle Scholar
  86. Hirschi KK, Rohovsky SA, D’Amore PA (1998) PDGF, TGF-β, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J Cell Biol 141:805–814PubMedCrossRefGoogle Scholar
  87. Hirschi KK, Rohovsky SA, Beck LH, Smith SR, D’Amore PA (1999) Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact. Circ Res 84:298–305PubMedGoogle Scholar
  88. Hirschi KK, Burt JM, Hirschi KD, Dai C (2003) Gap junction communication mediates transforming growth factor-β activation and endothelial-induced mural cell differentiation. Circ Res 93:429–437PubMedCrossRefGoogle Scholar
  89. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549–580PubMedCrossRefGoogle Scholar
  90. Hori S, Ohtsuki S, Hosoya K, Nakashima E, Terasaki T (2004) A pericyte-derived angiopoietin-1 multimeric complex induces occludin gene expression in brain capillary endothelial cells through Tie-2 activation in vitro. J Neurochem 89:503–513PubMedCrossRefGoogle Scholar
  91. Howson KM, Aplin AC, Gelati M, Alessandri G, Parati EA, Nicosia RF (2005) The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture. Am J Physiol Cell Physiol 289:C1396–C1407PubMedCrossRefGoogle Scholar
  92. Iurlaro M, Scatena M, Zhu WH, Fogel E, Wieting SL, Nicosia RF (2003) Rat aorta-derived mural precursor cells express the Tie2 receptor and respond directly to stimulation by angiopoietins. J Cell Sci 116:3635–3643PubMedCrossRefGoogle Scholar
  93. Jariyapongskul A, Nakano A, Yamaguchi S, Nageswari K, Niimi H (2003) Maturity of pericytes in cerebral neocapillaries induced by growth factors: fluorescence immuno-histochemical analysis using confocal laser microscopy. Clin Hemorheol Microcirc 29:417–421PubMedGoogle Scholar
  94. Jones N, Voskas D, Master Z, Sarao R, Jones J, Dumont DJ (2001) Rescue of the early vascular defects in Tek/Tie2 null mice reveals an essential survival function. EMBO Rep 2:438–445PubMedGoogle Scholar
  95. Kamouchi M, Kitazono T, Ago T, Wakisaka M, Ooboshi H, Ibayashi S, Iida M (2004) Calcium influx pathways in rat CNS pericytes. Brain Res Mol Brain Res 126:114–120PubMedCrossRefGoogle Scholar
  96. Kamouchi M, Kitazono T, Ago T, Wakisaka M, Kuroda J, Nakamura K, Hagiwara N, Ooboshi H, Ibayashi S, Iida M (2007) Hydrogen peroxide-induced Ca2+ responses in CNS pericytes. Neurosci Lett 416:12–16PubMedCrossRefGoogle Scholar
  97. Kano MR, Morishita Y, Iwata C, Iwasaka S, Watabe T, Ouchi Y, Miyazono K, Miyazawa K (2005) VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFRβ signaling. J Cell Sci 118:3759–3768PubMedCrossRefGoogle Scholar
  98. Kim H, Lee JM, Park JS, Jo SA, Kim YO, Kim CW, Jo I (2008) Dexamethasone coordinately regulates angiopoietin-1 and VEGF: a mechanism of glucocorticoid-induced stabilization of blood-brain barrier. Biochem Biophys Res Commun 372:243–248PubMedCrossRefGoogle Scholar
  99. Kim JH, Yu YS, Kim DH, Kim KW (2009) Recruitment of pericytes and astrocytes is closely related to the formation of tight junction in developing retinal vessels. J Neurosci Res 87:653–659PubMedCrossRefGoogle Scholar
  100. Kokovay E, Li L, Cunningham LA (2006) Angiogenic recruitment of pericytes from bone marrow after stroke. J Cereb Blood Flow Metab 26:545–555PubMedCrossRefGoogle Scholar
  101. Krueger M, Bechmann I (2010) CNS pericytes: concepts, misconceptions, and a way out. Glia 58:1–10PubMedCrossRefGoogle Scholar
  102. Kuijper S, Turner CJ, Adams RH (2007) Regulation of angiogenesis by Eph-ephrin interactions. Trends Cardiovasc Med 17:145–151PubMedCrossRefGoogle Scholar
  103. Kunz J, Krause D, Kremer M, Dermietzel R (1994) The 140-kDa protein of blood-brain barrier-associated pericytes is identical to aminopeptidase N. J Neurochem 62:2375–2386PubMedCrossRefGoogle Scholar
  104. Lai CH, Kuo KH (2005) The critical component to establish in vitro BBB model: Pericyte. Brain Res Brain Res Rev 50:258–265PubMedCrossRefGoogle Scholar
  105. Lamagna C, Bergers G (2006) The bone marrow constitutes a reservoir of pericyte progenitors. J Leukoc Biol 80:677–681PubMedCrossRefGoogle Scholar
  106. Larsson J, Goumans MJ, Sjostrand LJ, van Rooijen MA, Ward D, Leveen P, Xu X, ten Dijke P, Mummery CL, Karlsson S (2001) Abnormal angiogenesis but intact hematopoietic potential in TGF-β type I receptor-deficient mice. EMBO J 20:1663–1673PubMedCrossRefGoogle Scholar
  107. Lee TS, Hu KQ, Chao T, King GL (1989) Characterization of endothelin receptors and effects of endothelin on diacylglycerol and protein kinase C in retinal capillary pericytes. Diabetes 38:1643–1646PubMedCrossRefGoogle Scholar
  108. Li Q, Puro DG (2001) Adenosine activates ATP-sensitive K+ currents in pericytes of rat retinal microvessels: role of A1 and A2a receptors. Brain Res 907:93–99PubMedCrossRefGoogle Scholar
  109. Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP (1999) Defective angiogenesis in mice lacking endoglin. Science 284:1534–1537PubMedCrossRefGoogle Scholar
  110. Li JL, Sainson RC, Shi W, Leek R, Harrington LS, Preusser M, Biswas S, Turley H, Heikamp E, Hainfellner JA, Harris AL (2007) Delta-like 4 Notch ligand regulates tumor angiogenesis, improves tumor vascular function, and promotes tumor growth in vivo. Cancer Res 67:11244–11253PubMedCrossRefGoogle Scholar
  111. Lindahl P, Johansson BR, Leveen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245PubMedCrossRefGoogle Scholar
  112. Lindskog H, Athley E, Larsson E, Lundin S, Hellstrom M, Lindahl P (2006) New insights to vascular smooth muscle cell and pericyte differentiation of mouse embryonic stem cells in vitro. Arterioscler Thromb Vasc Biol 26:1457–1464PubMedCrossRefGoogle Scholar
  113. Liu Y, Wada R, Yamashita T, Mi Y, Deng CX, Hobson JP, Rosenfeldt HM, Nava VE, Chae SS, Lee MJ, Liu CH, Hla T, Spiegel S, Proia RL (2000) Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J Clin Invest 106:951–961PubMedCrossRefGoogle Scholar
  114. Liu H, Kennard S, Lilly B (2009) NOTCH3 expression is induced in mural cells through an autoregulatory loop that requires endothelial-expressed JAGGED1. Circ Res 104:466–475PubMedCrossRefGoogle Scholar
  115. Lombard JH (2006) A novel mechanism for regulation of retinal blood flow by lactate: gap junctions, hypoxia, and pericytes. Am J Physiol Heart Circ Physiol 290:H921–H922PubMedCrossRefGoogle Scholar
  116. MacFadyen J, Savage K, Wienke D, Isacke CM (2007) Endosialin is expressed on stromal fibroblasts and CNS pericytes in mouse embryos and is downregulated during development. Gene Expr Patterns 7:363–369PubMedCrossRefGoogle Scholar
  117. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60PubMedCrossRefGoogle Scholar
  118. Mathiisen TM, Lehre KP, Danbolt NC, Ottersen OP (2010) The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 58:1094–1103PubMedCrossRefGoogle Scholar
  119. Matsugi T, Chen Q, Anderson DR (1997) Contractile responses of cultured bovine retinal pericytes to angiotensin II. Arch Ophthalmol 115:1281–1285PubMedGoogle Scholar
  120. McGinty A, Scholfield CN, Liu WH, Anderson P, Hoey DE, Trimble ER (1999) Effect of glucose on endothelin-1-induced calcium transients in cultured bovine retinal pericytes. J Biol Chem 274:25250–25253PubMedCrossRefGoogle Scholar
  121. Mitchell TS, Bradley J, Robinson GS, Shima DT, Ng YS (2008) RGS5 expression is a quantitative measure of pericyte coverage of blood vessels. Angiogenesis 11:141–151PubMedCrossRefGoogle Scholar
  122. Morgan J, Muntoni F (2007) Mural cells paint a new picture of muscle stem cells. Nat Cell Biol 9:249–251PubMedCrossRefGoogle Scholar
  123. Nakagawa S, Deli MA, Nakao S, Honda M, Hayashi K, Nakaoke R, Kataoka Y, Niwa M (2007) Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. Cell Mol Neurobiol 27:687–694PubMedCrossRefGoogle Scholar
  124. Nakagawa S, Deli MA, Kawaguchi H, Shimizudani T, Shimono T, Kittel A, Tanaka K, Niwa M (2009) A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochem Int 54:253–263PubMedCrossRefGoogle Scholar
  125. Nakamura K, Kamouchi M, Kitazono T, Kuroda J, Matsuo R, Hagiwara N, Ishikawa E, Oobosi H, Ibayashi S, Iida M (2008) Role of NHE1 in calcium signaling and cell proliferation in human CNS pericytes. Am J Physiol Heart Circ Physiol 294:H1700–H1707PubMedCrossRefGoogle Scholar
  126. Nakamura K, Kamouchi M, Kitazono T, Kuroda J, Shono Y, Hagiwara N, Ago T, Ooboshi H, Ibayashi S, Iida M (2009) Amiloride inhibits hydrogen peroxide-induced Ca2+ responses in human CNS pericytes. Microvasc Res 77:327–334PubMedCrossRefGoogle Scholar
  127. Nayak RC, Berman AB, George KL, Eisenbarth GS, King GL (1988) A monoclonal antibody (3G5)-defined ganglioside antigen is expressed on the cell surface of microvascular pericytes. J Exp Med 167:1003–1015PubMedCrossRefGoogle Scholar
  128. Nehls V, Drenckhahn D (1991) Heterogeneity of microvascular pericytes for smooth muscle type α-actin. J Cell Biol 113:147–154PubMedCrossRefGoogle Scholar
  129. Nisancioglu MH, Mahoney WM Jr, Kimmel DD, Schwartz SM, Betsholtz C, Genove G (2008) Generation and characterization of RGS5 mutant mice. Mol Cell Biol 28:2324–2331PubMedCrossRefGoogle Scholar
  130. Nissen LJ, Cao R, Hedlund EM, Wang Z, Zhao X, Wetterskog D, Funa K, Brakenhielm E, Cao Y (2007) Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. J Clin Invest 117:2766–2777PubMedCrossRefGoogle Scholar
  131. Noguera-Troise I, Daly C, Papadopoulos NJ, Coetzee S, Boland P, Gale NW, Lin HC, Yancopoulos GD, Thurston G (2006) Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 444:1032–1037PubMedCrossRefGoogle Scholar
  132. Nomura M, Yamagishi S, Harada S, Hayashi Y, Yamashima T, Yamashita J, Yamamoto H (1995) Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes. J Biol Chem 270:28316–28324PubMedCrossRefGoogle Scholar
  133. Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (2000) Activin receptor-like kinase 1 modulates transforming growth factor-β 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci USA 97:2626–2631PubMedCrossRefGoogle Scholar
  134. Oishi K, Kamiyashiki T, Ito Y (2007) Isometric contraction of microvascular pericytes from mouse brain parenchyma. Microvasc Res 73:20–28PubMedCrossRefGoogle Scholar
  135. Okazaki T, Ni A, Baluk P, Ayeni OA, Kearley J, Coyle AJ, Humbles A, McDonald DM (2009) Capillary defects and exaggerated inflammatory response in the airways of EphA2-deficient mice. Am J Pathol 174:2388–2399PubMedCrossRefGoogle Scholar
  136. Ozerdem U, Stallcup WB (2003) Early contribution of pericytes to angiogenic sprouting and tube formation. Angiogenesis 6:241–249PubMedCrossRefGoogle Scholar
  137. Ozerdem U, Stallcup WB (2004) Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan. Angiogenesis 7:269–276PubMedCrossRefGoogle Scholar
  138. Paik JH, Skoura A, Chae SS, Cowan AE, Han DK, Proia RL, Hla T (2004) Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. Genes Dev 18:2392–2403PubMedCrossRefGoogle Scholar
  139. Pallone TL, Huang JM (2002) Control of descending vasa recta pericyte membrane potential by angiotensin II. Am J Physiol Renal Physiol 282:F1064–F1074PubMedGoogle Scholar
  140. Pallone TL, Silldorff EP, Zhang Z (2000) Inhibition of calcium signaling in descending vasa recta endothelia by ANG II. Am J Physiol Heart Circ Physiol 278:H1248–H1255PubMedGoogle Scholar
  141. Paquet-Fifield S, Schluter H, Li A, Aitken T, Gangatirkar P, Blashki D, Koelmeyer R, Pouliot N, Palatsides M, Ellis S, Brouard N, Zannettino A, Saunders N, Thompson N, Li J, Kaur P (2009) A role for pericytes as microenvironmental regulators of human skin tissue regeneration. J Clin Invest 119:2795–2806PubMedGoogle Scholar
  142. Parkinson FE, Hacking C (2005) Pericyte abundance affects sucrose permeability in cultures of rat brain microvascular endothelial cells. Brain Res 1049:8–14PubMedCrossRefGoogle Scholar
  143. Patan S (1998) TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth. Microvasc Res 56:1–21PubMedCrossRefGoogle Scholar
  144. Peppiatt CM, Howarth C, Mobbs P, Attwell D (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443:700–704PubMedCrossRefGoogle Scholar
  145. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD (2006) Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 1:223–236PubMedCrossRefGoogle Scholar
  146. Piquer-Gil M, Garcia-Verdugo JM, Zipancic I, Sanchez MJ, Alvarez-Dolado M (2009) Cell fusion contributes to pericyte formation after stroke. J Cereb Blood Flow Metab 29:480–485PubMedCrossRefGoogle Scholar
  147. Puri MC, Partanen J, Rossant J, Bernstein A (1999) Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development. Development 126:4569–4580PubMedGoogle Scholar
  148. Puro DG (2007) Physiology and pathobiology of the pericyte-containing retinal microvasculature: new developments. Microcirculation 14:1–10PubMedCrossRefGoogle Scholar
  149. Rajantie I, Ilmonen M, Alminaite A, Ozerdem U, Alitalo K, Salven P (2004) Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells. Blood 104:2084–2086PubMedCrossRefGoogle Scholar
  150. Reddy K, Cao Y, Zhou Z, Yu L, Jia SF, Kleinerman ES (2008a) VEGF165 expression in the tumor microenvironment influences the differentiation of bone marrow-derived pericytes that contribute to the Ewing’s sarcoma vasculature. Angiogenesis 11:257–267PubMedCrossRefGoogle Scholar
  151. Reddy K, Zhou Z, Schadler K, Jia SF, Kleinerman ES (2008b) Bone marrow subsets differentiate into endothelial cells and pericytes contributing to Ewing’s tumor vessels. Mol Cancer Res 6:929–936PubMedCrossRefGoogle Scholar
  152. Reinmuth N, Liu W, Ahmad SA, Fan F, Stoeltzing O, Parikh AA, Bucana CD, Gallick GE, Nickols MA, Westlin WF, Ellis LM (2003) αvβ3 integrin antagonist S247 decreases colon cancer metastasis and angiogenesis and improves survival in mice. Cancer Res 63:2079–2087PubMedGoogle Scholar
  153. Rouget C (1873) Memoire sur le developpement, la structure et les proprietes physiologiques des capillaries sanguins et lymphatiques. Arch Physiol Norm Pathol 5:603–661Google Scholar
  154. Rouget C (1879) Sur la contractilite des capillaires sanguins. CR Acad Sci 88:916–918Google Scholar
  155. Rucker HK, Wynder HJ, Thomas WE (2000) Cellular mechanisms of CNS pericytes. Brain Res Bull 51:363–369PubMedCrossRefGoogle Scholar
  156. Sainson RC, Harris AL (2007) Anti-Dll4 therapy: can we block tumour growth by increasing angiogenesis? Trends Mol Med 13:389–395PubMedCrossRefGoogle Scholar
  157. Sainson RC, Harris AL (2008) Regulation of angiogenesis by homotypic and heterotypic notch signalling in endothelial cells and pericytes: from basic research to potential therapies. Angiogenesis 11:41–51PubMedCrossRefGoogle Scholar
  158. Sakagami K, Wu DM, Puro DG (1999) Physiology of rat retinal pericytes: modulation of ion channel activity by serum-derived molecules. J Physiol 521(Pt 3):637–650PubMedCrossRefGoogle Scholar
  159. Salvucci O, Maric D, Economopoulou M, Sakakibara S, Merlin S, Follenzi A, Tosato G (2009) EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structures. Blood 114:1707–1716PubMedCrossRefGoogle Scholar
  160. Sato Y, Rifkin DB (1989) Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-β 1-like molecule by plasmin during co-culture. J Cell Biol 109:309–315PubMedCrossRefGoogle Scholar
  161. Sato Y, Tsuboi R, Lyons R, Moses H, Rifkin DB (1990) Characterization of the activation of latent TGF-β by co-cultures of endothelial cells and pericytes or smooth muscle cells: a self-regulating system. J Cell Biol 111:757–763PubMedCrossRefGoogle Scholar
  162. Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, Gridley T, Wolburg H, Risau W, Qin Y (1995) Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 376:70–74PubMedCrossRefGoogle Scholar
  163. Saunders WB, Bohnsack BL, Faske JB, Anthis NJ, Bayless KJ, Hirschi KK, Davis GE (2006) Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J Cell Biol 175:179–191PubMedCrossRefGoogle Scholar
  164. Scehnet JS, Jiang W, Kumar SR, Krasnoperov V, Trindade A, Benedito R, Djokovic D, Borges C, Ley EJ, Duarte A, Gill PS (2007) Inhibition of Dll4-mediated signaling induces proliferation of immature vessels and results in poor tissue perfusion. Blood 109:4753–4760PubMedCrossRefGoogle Scholar
  165. Schlingemann RO, Oosterwijk E, Wesseling P, Rietveld FJ, Ruiter DJ (1996) Aminopeptidase A is a constituent of activated pericytes in angiogenesis. J Pathol 179:436–442PubMedCrossRefGoogle Scholar
  166. Semela D, Das A, Langer D, Kang N, Leof E, Shah V (2008) Platelet-derived growth factor signaling through ephrin-B2 regulates hepatic vascular structure and function. Gastroenterology 135:671–679PubMedCrossRefGoogle Scholar
  167. Shepro D, Morel NM (1993) Pericyte physiology. FASEB J 7:1031–1038PubMedGoogle Scholar
  168. Shih SC, Ju M, Liu N, Mo JR, Ney JJ, Smith LE (2003) Transforming growth factor β1 induction of vascular endothelial growth factor receptor 1: mechanism of pericyte-induced vascular survival in vivo. Proc Natl Acad Sci USA 100:15859–15864PubMedCrossRefGoogle Scholar
  169. Shim WS, Ho IA, Wong PE (2007) Angiopoietin: a TIE(d) balance in tumor angiogenesis. Mol Cancer Res 5:655–665PubMedCrossRefGoogle Scholar
  170. Shimizu F, Sano Y, Maeda T, Abe MA, Nakayama H, Takahashi R, Ueda M, Ohtsuki S, Terasaki T, Obinata M, Kanda T (2008) Peripheral nerve pericytes originating from the blood-nerve barrier expresses tight junctional molecules and transporters as barrier-forming cells. J Cell Physiol 217:388–399PubMedCrossRefGoogle Scholar
  171. Sieczkiewicz GJ, Herman IM (2003) TGF-β 1 signaling controls retinal pericyte contractile protein expression. Microvasc Res 66:190–196PubMedCrossRefGoogle Scholar
  172. Silva R, D’Amico G, Hodivala-Dilke KM, Reynolds LE (2008) Integrins: the keys to unlocking angiogenesis. Arterioscler Thromb Vasc Biol 28:1703–1713PubMedCrossRefGoogle Scholar
  173. Simonavicius N, Robertson D, Bax DA, Jones C, Huijbers IJ, Isacke CM (2008) Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma. Mod Pathol 21:308–315PubMedCrossRefGoogle Scholar
  174. Smith MW, Gumbleton M (2006) Endocytosis at the blood-brain barrier: from basic understanding to drug delivery strategies. J Drug Target 14:191–214PubMedCrossRefGoogle Scholar
  175. Song S, Ewald AJ, Stallcup W, Werb Z, Bergers G (2005) PDGFRβ+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 7:870–879PubMedCrossRefGoogle Scholar
  176. Song N, Huang Y, Shi H, Yuan S, Ding Y, Song X, Fu Y, Luo Y (2009) Overexpression of platelet-derived growth factor-BB increases tumor pericyte content via stromal-derived factor-1α/CXCR4 axis. Cancer Res 69:6057–6064PubMedCrossRefGoogle Scholar
  177. Sorensen LK, Brooke BS, Li DY, Urness LD (2003) Loss of distinct arterial and venous boundaries in mice lacking endoglin, a vascular-specific TGFβ coreceptor. Dev Biol 261:235–250PubMedCrossRefGoogle Scholar
  178. Stallcup WB, Huang FJ (2008) A role for the NG2 proteoglycan in glioma progression. Cell Adh Migr 2:192–201PubMedCrossRefGoogle Scholar
  179. Stockmann C, Doedens A, Weidemann A, Zhang N, Takeda N, Greenberg JI, Cheresh DA, Johnson RS (2008) Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature 456:814–818PubMedCrossRefGoogle Scholar
  180. Stratman AN, Malotte KM, Mahan RD, Davis MJ, Davis GE (2009a) Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood 114:5091–5101PubMedCrossRefGoogle Scholar
  181. Stratman AN, Saunders WB, Sacharidou A, Koh W, Fisher KE, Zawieja DC, Davis MJ, Davis GE (2009b) Endothelial cell lumen and vascular guidance tunnel formation requires MT1-MMP-dependent proteolysis in 3-dimensional collagen matrices. Blood 114:237–247PubMedCrossRefGoogle Scholar
  182. Sundberg C, Kowanetz M, Brown LF, Detmar M, Dvorak HF (2002) Stable expression of angiopoietin-1 and other markers by cultured pericytes: phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo. Lab Invest 82:387–401PubMedCrossRefGoogle Scholar
  183. Sundberg C, Friman T, Hecht LE, Kuhl C, Solomon KR (2009) Two different PDGF β-receptor cohorts in human pericytes mediate distinct biological endpoints. Am J Pathol 175:171–189PubMedCrossRefGoogle Scholar
  184. 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 87:1171–1180PubMedCrossRefGoogle Scholar
  185. Takagi H, King GL, Aiello LP (1996) Identification and characterization of vascular endothelial growth factor receptor (Flt) in bovine retinal pericytes. Diabetes 45:1016–1023PubMedCrossRefGoogle Scholar
  186. Takahashi K, Brooks RA, Kanse SM, Ghatei MA, Kohner EM, Bloom SR (1989) Production of endothelin 1 by cultured bovine retinal endothelial cells and presence of endothelin receptors on associated pericytes. Diabetes 38:1200–1202PubMedCrossRefGoogle Scholar
  187. Takata F, Dohgu S, Yamauchi A, Sumi N, Nakagawa S, Naito M, Tsuruo T, Shuto H, Kataoka Y (2007) Inhibition of transforming growth factor-β production in brain pericytes contributes to cyclosporin A-induced dysfunction of the blood-brain barrier. Cell Mol Neurobiol 27:317–328PubMedCrossRefGoogle Scholar
  188. Takuwa Y, Okamoto Y, Yoshioka K, Takuwa N (2008) Sphingosine-1-phosphate signaling and biological activities in the cardiovascular system. Biochim Biophys Acta 1781:483–488PubMedGoogle Scholar
  189. Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, Tallquist MD, Graff JM (2008) White fat progenitor cells reside in the adipose vasculature. Science 322:583–586PubMedCrossRefGoogle Scholar
  190. Thomas WE (1999) Brain macrophages: on the role of pericytes and perivascular cells. Brain Res Brain Res Rev 31:42–57PubMedCrossRefGoogle Scholar
  191. Tigges U, Hyer EG, Scharf J, Stallcup WB (2008) FGF2-dependent neovascularization of subcutaneous Matrigel plugs is initiated by bone marrow-derived pericytes and macrophages. Development 135:523–532PubMedCrossRefGoogle Scholar
  192. Tillet E, Vittet D, Feraud O, Moore R, Kemler R, Huber P (2005) N-cadherin deficiency impairs pericyte recruitment, and not endothelial differentiation or sprouting, in embryonic stem cell-derived angiogenesis. Exp Cell Res 310:392–400PubMedCrossRefGoogle Scholar
  193. Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, Johnstone BH, March KL (2008) A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res 102:77–85PubMedCrossRefGoogle Scholar
  194. Urness LD, Sorensen LK, Li DY (2000) Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet 26:328–331PubMedCrossRefGoogle Scholar
  195. van Hinsbergh VW, Engelse MA, Quax PH (2006) Pericellular proteases in angiogenesis and vasculogenesis. Arterioscler Thromb Vasc Biol 26:716–728PubMedCrossRefGoogle Scholar
  196. Verbeek MM, Otte-Holler I, Wesseling P, Ruiter DJ, de Waal RM (1994) Induction of α-smooth muscle actin expression in cultured human brain pericytes by transforming growth factor-β 1. Am J Pathol 144:372–382PubMedGoogle Scholar
  197. Vikkula M, Boon LM, Carraway KL 3rd, 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 87:1181–1190PubMedCrossRefGoogle Scholar
  198. Virgintino D, Girolamo F, Errede M, Capobianco C, Robertson D, Stallcup WB, Perris R, Roncali L (2007) An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis. Angiogenesis 10:35–45PubMedCrossRefGoogle Scholar
  199. von Tell D, Armulik A, Betsholtz C (2006) Pericytes and vascular stability. Exp Cell Res 312:623–629CrossRefGoogle Scholar
  200. Wakisaka M, Kitazono T, Kato M, Nakamura U, Yoshioka M, Uchizono Y, Yoshinari M (2001) Sodium-coupled glucose transporter as a functional glucose sensor of retinal microvascular circulation. Circ Res 88:1183–1188PubMedCrossRefGoogle Scholar
  201. Wakui S, Furusato M, Muto T, Ohshige H, Takahashi H, Ushigome S (1997) Transforming growth factor-β and urokinase plasminogen activator presents at endothelial cell-pericyte interdigitation in human granulation tissue. Microvasc Res 54:262–269PubMedCrossRefGoogle Scholar
  202. Wakui S, Yokoo K, Muto T, Suzuki Y, Takahashi H, Furusato M, Hano H, Endou H, Kanai Y (2006) Localization of Ang-1, -2, Tie-2, and VEGF expression at endothelial-pericyte interdigitation in rat angiogenesis. Lab Invest 86:1172–1184PubMedGoogle Scholar
  203. Wang YL, Hui YN, Guo B, Ma JX (2007) Strengthening tight junctions of retinal microvascular endothelial cells by pericytes under normoxia and hypoxia involving angiopoietin-1 signal way. Eye 21:1501–1510PubMedCrossRefGoogle Scholar
  204. Watanabe S, Morisaki N, Tezuka M, Fukuda K, Ueda S, Koyama N, Yokote K, Kanzaki T, Yoshida S, Saito Y (1997) Cultured retinal pericytes stimulate in vitro angiogenesis of endothelial cells through secretion of a fibroblast growth factor-like molecule. Atherosclerosis 130:101–107PubMedCrossRefGoogle Scholar
  205. Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553–563PubMedGoogle Scholar
  206. Wu DM, Kawamura H, Sakagami K, Kobayashi M, Puro DG (2003) Cholinergic regulation of pericyte-containing retinal microvessels. Am J Physiol Heart Circ Physiol 284:H2083–H2090PubMedGoogle Scholar
  207. Yamanishi S, Katsumura K, Kobayashi T, Puro DG (2006) Extracellular lactate as a dynamic vasoactive signal in the rat retinal microvasculature. Am J Physiol Heart Circ Physiol 290:H925–H934PubMedCrossRefGoogle Scholar
  208. Yan Q, Sage EH (1998) Transforming growth factor-β1 induces apoptotic cell death in cultured retinal endothelial cells but not pericytes: association with decreased expression of p21waf1/cip1. J Cell Biochem 70:70–83PubMedCrossRefGoogle Scholar
  209. Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T (2009) Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med 15:1031–1037PubMedCrossRefGoogle Scholar
  210. Yonekura H, Sakurai S, Liu X, Migita H, Wang H, Yamagishi S, Nomura M, Abedin MJ, Unoki H, Yamamoto Y, Yamamoto H (1999) Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes. Implication in autocrine and paracrine regulation of angiogenesis. J Biol Chem 274:35172–35178PubMedCrossRefGoogle Scholar
  211. Zhang J, Cao R, Zhang Y, Jia T, Cao Y, Wahlberg E (2009) Differential roles of PDGFR-α and PDGFR-β in angiogenesis and vessel stability. FASEB J 23:153–163PubMedCrossRefGoogle Scholar
  212. Zimmerman K (1923) Der peinere bau der blutcapillaren. A Anat Entwicklungsgesch 68:29–109CrossRefGoogle Scholar
  213. Zlokovic BV (2006) Remodeling after stroke. Nat Med 12:390–391PubMedCrossRefGoogle Scholar
  214. Zlokovic BV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178–201PubMedCrossRefGoogle Scholar
  215. Zozulya A, Weidenfeller C, Galla HJ (2008) Pericyte-endothelial cell interaction increases MMP-9 secretion at the blood-brain barrier in vitro. Brain Res 1189:1–11PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Masahiro Kamouchi
    • 1
  • Tetsuro Ago
    • 1
  • Takanari Kitazono
    • 1
  1. 1.Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityHigashi-kuJapan

Personalised recommendations