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ECM Remodeling in Angiogenesis

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Mechanical and Chemical Signaling in Angiogenesis

Part of the book series: Studies in Mechanobiology, Tissue Engineering and Biomaterials ((SMTEB,volume 12))

Abstract

Remodeling of the extracellular matrix (ECM) is an essential component of the complex vascular biology that drives each step within the angiogenic cascade. The process of angiogenesis involves a series of events that depend heavily on proteinases and their ability to remodel the ECM, originating with degradation of the basement membrane to allow for endothelial cell (EC) breakthrough, migration, and proliferation. This is followed by organization into nascent blood vessel sprouts, vessel maturation and stabilization, deposition of basement membrane around the new vessels, and finally pruning or remodeling of the new vasculature for physiological needs. There is evidence that ECs cooperate with supporting stromal cells to orchestrate these remodeling events and ultimately to create pericyte-stabilized functional networks of vessels. During angiogenesis, proteinases not only directly breakdown the ECM to create a physical path for new EC sprouts, they also indirectly expose cryptic sites hidden within the ECM to alter the adhesive microenvironment for pericytes and endothelial cells during sprouting. Physiological control of angiogenesis is achieved in part by the angiogenic switch, in which a balance of pro- and anti-angiogenic factors serves to maintain vessel homeostasis under normal conditions. Proteinases, and certain matrix metalloproteinases (MMPs) in particular, function on both sides of the angiogenic switch. They degrade the basement membrane and nearby ECM surrounding established blood vessels at the onset of angiogenesis, and release pro-angiogenic growth factors that would remain otherwise bound to the ECM. However, they also negatively control angiogenesis, as some proteolytic fragments of the ECM possess anti-angiogenic properties. In addition to the chemical specificity of proteinases, emerging evidence suggests that their ability to proteolytically remodel the ECM during angiogenesis may also depend on the physical properties of the ECM. In this chapter, we will discuss the important factors that govern ECM remodeling during angiogenesis, focusing on the links between proteinases, stromal cells, and matrix physical properties. The impact of these possible links on therapeutic and pathologic angiogenesis will also be discussed.

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References

  1. Jain, R.: Molecular regulation of vessel maturation. Nat. Med. 9, 685–693 (2003)

    Google Scholar 

  2. Carmeliet, P., Jain, R.: Angiogenesis in cancer and other diseases. Nature 407, 249–257 (2000)

    Google Scholar 

  3. Adams, R., Alitalo, K.: Molecular regulation of angiogenesis and lymphangiogenesis. Nat. Rev. Mol. Cell Biol. 8, 464–478 (2007)

    Google Scholar 

  4. Page-McCaw, A., Ewalk, A., Werb, Z.: Matrix metalloproteinases and the regulation of tissue remodeling. Nat. Rev. Mol. Cell. Biol. 8, 221–233 (2007)

    Google Scholar 

  5. Ghajar, C., George, S., Putnam, A.: Matrix metalloproteinase control of capillary morphogenesis. Crit. Rev. Eukaryot. Gene. Expr. 18(3), 251–278 (2008)

    Google Scholar 

  6. Ausprunk, D., Folkman, J.: Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc. Res. 14, 53–65 (1977)

    Google Scholar 

  7. Davis, G., Senger, D.: Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ. Res. 97, 1093–1107 (2005)

    Google Scholar 

  8. Roovers, K., Assoian, R.: Integrating the MAP kinase signal into the G1 phase cell cycle machinery. Bioessays 22, 818–826 (2000)

    Google Scholar 

  9. Seger, R., Krebs, E.: The MAPK signaling cascade. FASEB J. 9, 726–735 (1995)

    Google Scholar 

  10. Vinals, F., Pouyssegur, J.: Confluence of vascular endothelial cells induces cell cycle exit by inhibiting p42/p44 mitogen-activated protein kinase activity. Mol. Cell. Biol. 19, 2763–2772 (1999)

    Google Scholar 

  11. Assoian, R., Schwartz, M.: Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression. Curr. Opin. Genet. Dev. 11, 48–53 (2001)

    Google Scholar 

  12. Akiyama, S., Yamada, S., Chen, W., Yamada, K.: Analysis of fibronectin receptor function with monoclonal antibodies: roles in cell adhesion, migration, matrix assembly, and cytoskeletal organization. J. Cell Biol. 109, 863–875 (1989)

    Google Scholar 

  13. Meredith, J., Schwartz, M.: Integrins, adhesion and apoptosis. Trends Cell Biol. 7, 146–150 (1997)

    Google Scholar 

  14. Giancotti, F., Ruoslahti, R.: Integrin signaling. Science 285, 1028–1032 (1999)

    Google Scholar 

  15. Wary, K., Mainiero, F., Isakoff, S., Marcantonion, E., Giancotti, F.: The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Cell 87, 733–743 (1996)

    Google Scholar 

  16. Liu, Y., Senger, D.: Matrix-specific activation of Src and Rho initiates capillary morphogenesis of endothelial cells. FASEB J. 18, 457–468 (2004)

    Google Scholar 

  17. Davis, G., Bayless, K., Mavila, A.: Molecular basis of endothelial cell morphogenesis in three-dimensional extracellular matrices. Anat. Rec. 268, 252–275 (2002)

    Google Scholar 

  18. Vernon, R., Sage, H.: A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices. Microvasc. Res. 57(2), 118–133 (1999)

    Google Scholar 

  19. Ingber, D., Folkman, J.: Inhibition of angiogenesis through modulation of collagen metabolism. Lab Invest. 59, 44–51 (1988)

    Google Scholar 

  20. Whelan, M., Senger, D.: Collagen I initiates endothelial cell morphogenesis by inducing actin polymerization through suppression of cyclic AMP and protein kinase A. J. Biol. Chem. 278, 327–334 (2003)

    Google Scholar 

  21. Montesano, R., Orci, L., Vassalli, P.: In vitro rapid organization of endothelial cells into capillary-like networks is promotoed by collagen matrices. J. Cell Biol. 97, 1648–1652 (1983)

    Google Scholar 

  22. Senger, D., Perruzzi, C., Streit, M., Koteliansky, V., Fougerolles, A.d., Detmar, M.: The alpha1beta1 and alpha2beta1 integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis. Am. J. Pathhol. 160, 195–204 (2002)

    Google Scholar 

  23. Davis, G., Camarillo, C.: An alpha2beta1 integrin-dependent pinocytic mechanism involving intracellular vacuole formation and coalescence regulates capillary lumen and tube formation in three-dimensional collagen matrix. Exp. Cell Res. 224, 39–51 (1996)

    Google Scholar 

  24. Senger, D., Claffey, K., Benes, J., Perruzzi, C., Sergiou, A., Detmar, M.: Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins. Proc. Natl. Acad. Sci. USA 94, 13612–13617 (1997)

    Google Scholar 

  25. Bayless, J., Davis, G.: The Cdc42 and Rac1 GTPases are required for capillary lumen formation in three-dimensional extracellular matrices. J. Cell Sci. 115, 1123–1136 (2002)

    Google Scholar 

  26. Davis, G., Bayless, K.: An integrin and Rho GTPase-dependent pinocytic vacuole mechanism controls capillary lumen formation in collagen and fibrin matrices. Microcirculation 10, 27–44 (2003)

    Google Scholar 

  27. Yurchenco, P., Amenta, P., Patton, B.: Basement membrane assembly, stability and activities observed through a developmental lens. Matrix Biol. 276, 521–538 (2004)

    Google Scholar 

  28. Fujiwara, H., Kikkawa, Y., Sanzen, N., Sekiguchi, K.: Purification and characterization of human laminin-8. Laminin-8 stimulates cell adhesion and migration through alpha3beta1 and alpha6beta1 integrins. J. Biol. Chem. 276, 17550–17558 (2001)

    Google Scholar 

  29. Mettouchi, A., Klein, S., Guo, W., Lopez-Lago, M., Lemichez, E., Westwick, J., Giancotti, F.: Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle. Mol. Cell. 8, 115–127 (2001)

    Google Scholar 

  30. Klein, S., de Fougerolles, A.R., Blaikie, P., Khan, L., Pepe, A., Green, C., Koteliansky, V., Giancotti, F.: Alpha5 beta1 integrin activates an NF-kappa B-dependent program of gene expression important for angiogenesis and inflammation. Mol. Cell. Biol. 22, 5912–5922 (2002)

    Google Scholar 

  31. Nagase, H., Woessner, J.: Matrix metalloproteinases. J. Biol. Chem. 274, 21491–21494 (1999)

    Google Scholar 

  32. Stamenkovic, I.: Extracellular matrix remodeling: the role of matrix metalloproteinases. J. Pathol. 200, 448–464 (2003)

    Google Scholar 

  33. Sternlicht, M., Werb, Z.: How matrix metalloproteinases regulate cell behavior. Ann. Rev. Cell Dev. Biol. 17, 463–516 (2001)

    Google Scholar 

  34. van Hinsbergh, V., Englese, M., Quax, P.: Pericellular proteases in angiogenesis and vasculogenesis. Arterioscler. Thromb. Vasc. Biol. 26, 716–728 (2006)

    Google Scholar 

  35. Bode, W., Fernandez-Catalan, C., Tschesche, H., Grams, F., Nagase, H., Maskos, K.: Structural properties of matrix metalloproteinases. Cell. Mol. Life Sci. 55, 639–652 (1999)

    Google Scholar 

  36. Kleiner, D., Stetler-Stevenson, W.: Structural biochemistry and activation of matrix metalloproteinases. Curr. Opin. Cell Biol. 5, 891–897 (1993)

    Google Scholar 

  37. McCawley, L., Matrisian, L.: Matrix metalloproteinases: they’re not just for matrix anymore! Curr. Opin. Cell Biol. 13, 534–540 (2001)

    Google Scholar 

  38. Lynch, C., Matrisian, L.: Matrix metalloproteinases in tumor-hose cell communication. Differentiation 70, 561–573 (2002)

    Google Scholar 

  39. Lee, M.-H., Murphy, G.: Matrix metalloproteinases at a glance. J. Cell Sci. 117, 4015–4016 (2004)

    Google Scholar 

  40. Visse, R., Nagase, H.: Matrix metalloproteinases and tissue inhibitors or metalloproteinases. Circ. Res. 92, 827–839 (2003)

    Google Scholar 

  41. Taraboletti, G., D’Ascenzo, S., Borsotti, P., Giavazzi, R., Pavan, A., Dolo, V.: Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. Am. J. Pathol. 160(2), 673–680 (2002)

    Google Scholar 

  42. Li, A., Dubey, S., Varney, M., Dave, B., Singh, R.: IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinase production and regulated angiogenesis. J. Immunol. 170, 3369–3376 (2003)

    Google Scholar 

  43. Nguyen, M., Arkell, J., Jackson, C.: Human endothelial gelatinases and angiogenesis. Int. J. Biochem. Cell Biol. 33, 960–970 (2001)

    Google Scholar 

  44. Nyberg, P., Xie, L., Kalluri, R.: Endogenous inhibitors of angiogenesis. Cancer Cell 3, 589–601 (2005)

    Google Scholar 

  45. Yana, I., Sagara, H., Takaki, S., Takatsu, K., Nakamura, K., Nakao, K., Katsuki, M., Taniguchi, S., Aoki, T., Sato, H., Weiss, S., Seiki, M.: Crosstalk between neovessels and mural cells directs the site-specific expression of MT1-MMP to endothelial tip cells. J. Cell Sci. 120, 1607–1614 (2007)

    Google Scholar 

  46. Kalluri, R.: Basement membranes: structure, assembly and role in tumor angiogenesis. Nat. Rev. Cancer 3, 422–433 (2003)

    Google Scholar 

  47. Jeong, J., Cha, H., Yu, D., Seiki, M., Kim, K.: Induction of membrane-type matrix metalloproteinase-1 stimulates angiogenic activities of bovine aortic endothelial cells. Angiogenesis 3, 167–174 (1999)

    Google Scholar 

  48. Tang, Y., Kesavan, P., Nakada, M., Yan, L.: Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol. Cancer Res. 2, 73–80 (2004)

    Google Scholar 

  49. Helm, C., Fleury, M., Zisch, A., Boschetti, F., Swartz, M.: Synergy between interstitial flow and VEGF directs capillary morphogenesis in vitro through a gradient amplification mechanism. Proc. Natl. Acad. Sci. USA 102, 15779–15784 (2005)

    Google Scholar 

  50. Carlson, M., Longaker, M.: The fibroblast-populated collagen matrix as a model of wound healing: a review of the evidence. Wound Repear Regen 12, 134–147 (2004)

    Google Scholar 

  51. Burbridge, M., Coge, F., Galizzi, J., Boutin, J., West, D., Tucker, G.: The role of the matrix metalloproteinases during in vitro vessel formation. Angiogenesis 5, 215–226 (2002)

    Google Scholar 

  52. Kachgal, S., Putnam, A.: Mesenchymal stem cells from adipose and bone marrow promote angiogenesis via distinct cytokine and protease expression mechanisms. Angiogenesis 14(1), 47–59 (2011)

    Google Scholar 

  53. Lee, S., Jilani, S., Nikolova, G., Carpizo, D., Iruela-Arispe, M.: Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J. Cell Biol. 169, 681–691 (2005)

    Google Scholar 

  54. Bergers, G., Brekken, R., McMahon, G., Vu, T., Itoh, T., Tamaki, K., Tanzawa, K., Thorpe, P., Itohara, S., Werb, Z., Hanahan, D.: Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat. Cell Biol. 2(10), 737–744 (2000)

    Google Scholar 

  55. Moses, M., Marikovsky, M., Harper, J., Vogt, P., Eriksson, E., Klagsbrun, M., Langer, R.: Temporal study of the activity of matrix metalloproteinases and their endogenous inhibitors during wound healing. J. Cell. Biochem. 60(3), 379–386 (1996)

    Google Scholar 

  56. Muhs, B., Plitas, G., Delgado, Y., Ianus, I., Shaw, J., Adelman, M., Lamparello, P., Shamamian, P., Gagne, P.: Temporal expression and activation of matrix metalloproteinases-2, -9, and membrane type 1-matrix metalloproteinase following acute hindlimb ischemia. J. Surg. Res. 111, 8–15 (2003)

    Google Scholar 

  57. Patterson, J., Hubbell, J.: Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2. Biomaterials 31, 7836–7845 (2010)

    Google Scholar 

  58. Moon, J., Saik, J., Poche, R., Leslie-Barbick, J., Lee, S., Smith, A., Dickinson, M., West, J.: Biomimetic hydrogels with pro-angiogenic properties. Biomaterials 31, 3840–3847 (2010)

    Google Scholar 

  59. Zisch, A., Lutolf, M., Ehrbar, M., Raeber, G., Rizzi, S., Davies, N., Schmokel, H., Bezuidenhout, D., Djonov, V., Zilla, P., Hubbell, J.: Cell-demanded release of VEGF from synthetic, biointeractive cell ingrowth matrices for vascularized tissue growth. FASEB J. 17(15), 2260–2262 (2003)

    Google Scholar 

  60. Davis, G., Allen, K., Salazar, R., Maxwell, S.: Matrix metalloproteinase-1 and -9 activation by plasmin regulates a novel endothelial cell-mediated mechanism of collagen gel contraction and capillary tube regression in three-dimensional collagen matrices. J. Cell Sci. 114, 917–930 (2001)

    Google Scholar 

  61. Zhu, W., Guo, X., Villaschi, S., Nicosia, R.: Regulation of vascular growth and regression by matrix metalloproteinases in the rat aorta model of angiogenesis. Lab. Invest. 80, 545–555 (2000)

    Google Scholar 

  62. Saunders, W., Bayless, J., Davis, G.: MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices. J. Cell Sci. 118, 2325–2340 (2005)

    Google Scholar 

  63. Davis, G., Saunders, W.: Molecular balance of capillary tube formation versus regression in wound repair: Role of matrix metalloproteinases and their inhibitors. J. Investig. Dermatol. Symp. Proc. 11, 44–56 (2006)

    Google Scholar 

  64. Hamano, Y., Zeisberg, M., Sugimoto, H., Lively, J., Maeshima, Y., Yang, C., Hynes, R., Werb, Z., Sudhakar, A., Kalluri, R.: Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell 3(6), 589–601 (2003)

    Google Scholar 

  65. Hangai, M., Kitaya, N., Xu, J., Chan, C., Kim, J., Werb, Z., Ryan, S., Brooks, P.: Matrix metalloproteinase-9-dependent exposure of a cryptic migratory control site in collagen is required before retinal angiogenesis. Am. J. Path. 161(4), 1429–1437 (2002)

    Google Scholar 

  66. Chang, J., Javier, J., Chang, G., Oliveira, H., Azar, D.: Functional characterization of neostatins, the MMP-derived, enzymatic cleavage products of type XVIII collagen. FEBS Lett. 579, 3601–3606 (2005)

    Google Scholar 

  67. Heljasvaara, R., Nyberg, P., Luostarinen, J., Parikka, M., Heikkila, P., Rehn, M., Sorsa, T., Salo, T., Pihlajaniemi, T.: Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases. Exp. Cell Res. 307(2), 292–304 (2005)

    Google Scholar 

  68. O’Reilly, M., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W., Flynn, E., Birkhead, J., Olsen, B., Folkman, J.: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88, 277–285 (1997)

    Google Scholar 

  69. Kim, Y., Jang, J., Lee, O., Yeon, J., Choi, E., Kim, K., Lee, S., Kwon, Y.: Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase 2. Cancer Res. 60, 5410–5413 (2000)

    Google Scholar 

  70. Vihinen, P., Kahari, V.-M.: Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets. Int. J. Cancer 99, 157–166 (2002)

    Google Scholar 

  71. Hellstrom, M., Gerhardt, H., Kalen, M., Li, X., Eriksson, U., Wolburg, H., Betsholtz, C.: Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J. Cell Biol. 153(3), 543–554 (2001)

    Google Scholar 

  72. Gerhardt, H., Betsholtz, C.: Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res. 314(1), 15–23 (2003)

    Google Scholar 

  73. Lehti, K., Birkedal-Hansen, E.A.H., Holmbeck, K., Miyake, Y., Chun, T., Weiss, S.: An MT1-MMP-PDGF receptor-beta axis regulates mural cell investment of the microvasculature. Genes Dev. 19, 979–991 (2005)

    Google Scholar 

  74. Ghajar, C.M., Kachgal, S., Kniazeva, E., Mori, H., Costes, S.V., George, S.C., Putnam, A.J.: Mesenchymal cells stimulate capillary morphogenesis via distinct proteolytic mechanisms. Exp. Cell Res. 316(5), 813–825 (2010)

    Google Scholar 

  75. Suri, C., Jones, P., Patan, S., Bartunkova, S., Mainsonpierre, P., Davis, S., Sato, T., Yancopoulos, G.: Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87, 1171–1180 (1996)

    Google Scholar 

  76. Kraling, B., Wiederschain, D., Boehm, T., Rehn, M., Mulliken, J., Moses, M.: The role of matrix metalloproteinase activity in the maturation of human capillary endothelial cells in vitro. J. Cell Sci. 112(Pt 10), 1599–1609 (1999)

    Google Scholar 

  77. Saunders, W., Bohnsack, B., Faske, J., Anthis, N., Bayless, K., Hirschi, K., Davis, G.: Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J. Cell Biol. 175(1), 179–191 (2006)

    Google Scholar 

  78. Lafleur, M., Forsyth, P., Atkinson, S., Murphy, G., Edwards, D.: Perivascular cells regulate endothelial membrane type-1 matrix metalloproteinase activity. Biochem. Biophys. Res. Commun. 282, 463–473 (2001)

    Google Scholar 

  79. Edwards, D., Handsley, M., Pennington, C.: The ADAM metalloproteinases. Mol. Aspects Med. 29(5), 258–289 (2008)

    Google Scholar 

  80. Roghani, M., Becherer, J., Moss, M., Atherton, R., Erdjument-Bromage, H., Arribas, J., Blackburn, R., Weskamp, G., Tempst, P., Blobel, C.: Metalloproteinase-disintegrin MDC9: intracellular maturation and catalytic activity. J. Biol. Chem. 6, 3531–3540 (1999)

    Google Scholar 

  81. Howard, L., Maciewicz, R., Blobel, C.: Cloning and characterization of ADAM28: evidence for autocatalytic pro-domain removal and for cell surface localization of mature ADAM28. Biochem. J. 348(Pt 1), 21–27 (2000)

    Google Scholar 

  82. Schlomann, U., Wildeboer, D., Webster, A., Antropova, O., Zeuschner, D., Knight, C., Docherty, A., Lambert, M., Skelton, L., Jockusch, H., Bartsch, J.: The metalloprotease disintegrin ADAM8. Processing by autocatalysis is required for proteolytic activity and cell adhesion. J. Biol. Chem. 50, 48210–48219 (2002)

    Google Scholar 

  83. White, J.: ADAMs: modulators of cell–cell and cell-matrix interactions. Curr. Opin. Cell Biol. 15(5), 598–606 (2003)

    Google Scholar 

  84. Niewiarowski, S., McLane, M., Kloczewiak, M., Stewart, G.: Disintegrins and other naturally occurring antagonists of platelet fibrinogen receptors. Semin. Hematol. 31(4), 289–300 (1994)

    Google Scholar 

  85. Mazzocca, A., Coppari, R., Franco, R.D., Cho, J., Libermann, T., Pinzani, M., Toker, A.: A secreted form of ADAM9 promotes carcinoma invasion through tumor-stromal interactions. Cancer Res. 65(11), 4728–4738 (2005)

    Google Scholar 

  86. Schulz, B., Pruessmeyer, J., Maretzky, T., Ludwig, A., Blobel, C., Saftig, P., Reiss, K.: ADAM10 regulates endothelial permeability and T-cell transmigration by proteolysis of vascular endothelial cadherin. Circ. Res. 102(10), 1192–1201 (2008)

    Google Scholar 

  87. Kenny, P., Bissell, M.: Targeting TACE-dependent EGFR ligand shedding in breast cancer. J. Clin. Invest. 117(2), 337–345 (2007)

    Google Scholar 

  88. Baker, A., Edwards, D., Murphy, G.: Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J. Cell Sci. 115, 3719–3727 (2002)

    Google Scholar 

  89. Chrico, R., Liu, X., Jung, K., Kim, H.: Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev. 25, 99–113 (2006)

    Google Scholar 

  90. Brew, K., Dinakarpandian, D., Nagase, H.: Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochem. Biophys. Acta 1477, 267–283 (2000)

    Google Scholar 

  91. Yu, W., Yu, S., Meng, Q., Brew, K., Woessner, J.: TIMP-3 binds to sulphated glycosaminoglycans of the extracellular matrix. J. Biol. Chem. 275, 31226–31232 (2000)

    Google Scholar 

  92. Will, H., Atkinson, S., Butler, G., Smith, B., Murphy, G.: The soluble catalytic domain of membrane type 1 matrix metalloproteinase cleaves the propeptide of progelatinase A and initiates autoproteolytic activation. Regulation by TIMP-2 and TIMP-3. J. Biol. Chem. 271, 17119–17123 (1996)

    Google Scholar 

  93. Amour, A., Knight, C., Webster, A., Slocombe, P., Stephens, P., Knauper, V., Docherty, A., Murphy, G.: The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3. FEBS Lett. 473, 275–279 (2000)

    Google Scholar 

  94. Goldberg, G., Marmer, B., Grant, G., Eisen, A., Wilhelm, S., He, C.: Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteinases designated TIMP-2. Proc. Natl. Acad. Sci. USA 86, 8207–8211 (1989)

    Google Scholar 

  95. Wilhelm, S., Collier, I., Marmer, B., Eisen, A., Grant, G., Goldberg, G.: SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J. Biol. Chem. 264(29), 17213–17221 (1989)

    Google Scholar 

  96. Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., Seiki, M.: A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature 370, 61–65 (1994)

    Google Scholar 

  97. Strongin, A., Collier, I., Bannikov, G., Marmer, B., Grant, G.: Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J. Biol. Chem. 270, 5331–5338 (1995)

    Google Scholar 

  98. Fernandez, C., Butterfield, C., Jackson, G., Moses, M.: Structural and functional uncoupling of the enzymatic and angiogenic inhibitory activities of tissue inhibitor metalloproteinase-2 (TIMP-2): loop 6 is a novel angiogenesis inhibitor. J. Biol. Chem. 278, 40989–40995 (2003)

    Google Scholar 

  99. Qi, J., Ebrahem, Q., Moore, N., Murphy, G., Claesson-Welsh, L., Bond, M., Baker, A., Anand-Apte, B.: A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat. Med. 9, 407–415 (2003)

    Google Scholar 

  100. Yu, W., Yu, S., Meng, Q., Brew, K., Woessner, J.: TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix. J. Biol. Chem. 275, 31226–31232 (2000)

    Google Scholar 

  101. Greene, J., Wang, M., Liu, Y., Raymond, L., Rosen, C., Shi, Y.: Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. J. Biol. Chem. 271(48), 30375–30380 (1996)

    Google Scholar 

  102. Fernandez, C., Moses, M.: Modulation of angiogenesis by tissue inhibitor of metalloproteinase-4. Biochem. Biophys. Res. Commun. 345, 523–529 (2006)

    Google Scholar 

  103. Koskivirta, I., Kassiri, Z., Rahkonen, O., Kiviranta, R., Oudir, G., McKee, T., Kyto, V., Saraste, A., Jokinen, E., Liu, P., Vuorio, E., Khokha, R.: Mice with tissue inhibitor of metalloproteinase 4 (Timp4) delection succumb to induced myocardial infarction but not to cardiac pressure overload. J. Biol. Chem. 285(32), 24487–24493 (2010)

    Google Scholar 

  104. Takahashi, C., Sheng, Z., Horan, T., Kitayama, H., Maki, M., Hitomi, K., Kitaura, Y., Takai, S., Sasahara, R., Horimoto, A., Ikawa, Y., Ratzkin, B., Arakawa, T., Noda, M.: Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proc. Natl. Acad. Sci. USA 95(22), 13221–13226 (1998)

    Google Scholar 

  105. Oh, J., Takahashi, R., Kondo, S., Mizoguchi, A., Adachi, E., Sasahara, R., Nishimura, S., Imamura, Y., Kitayama, H., Alexander, D., Ide, C., Horan, T., Arakawa, T., Yoshida, H., Nishikawa, S., Itoh, Y., Seiki, M., Itohara, S., Takahashi, C., Noda, M.: The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 107(6), 789–800 (2001)

    Google Scholar 

  106. Egeblad, M., Werb, Z.: New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2, 161–174 (2002)

    Google Scholar 

  107. Thurston, G.: Complementary actions of VEGF and Angiopoietin-1 on blood vessel growth and leakage. J. Anat. 200(6), 575–580 (2002)

    Google Scholar 

  108. Thomas, M., Augustin, H.: The role of the angiopoietins in vascular morphogenesis. Angiogenesis 12, 125–137 (2009)

    Google Scholar 

  109. Stratman, A., Malotte, K., Mahan, R., Davis, M., Davis, G.: Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood 114, 5091–5101 (2009)

    Google Scholar 

  110. Stratman, A., Saunders, W., Sacharidou, A., Koh, W., Fisher, K., Zawieja, D., Davis, M., Davis, G.: Endothelial cell lumen and vascular guidance tunnel formation requires MT1-MMP-dependent proteolysis in 3-dimensional collagen matrices. Blood 114, 237–247 (2009)

    Google Scholar 

  111. Stratman, A., Schwindt, A., Malotte, K., Davis, G.: Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization. Blood 116, 4720–4730 (2010)

    Google Scholar 

  112. Greenberg, J., Shields, D., Barillas, S., Acevedo, L., Murphy, E., Huang, J., Scheppke, L., Stockmann, C., Johnson, R., Angle, N., Charesh, D.: A role for VEGF as a negative regulator of pericyte function and vessel maturation. Nature 456(7223), 809–813 (2008)

    Google Scholar 

  113. Jain, R.: Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307, 58–62 (2005)

    Google Scholar 

  114. Miner, J., Yurchenco, P.: Laminin functions in tissue morphogenesis. Ann. Rev. Cell Dev. Biol. 20, 255–284 (2004)

    Google Scholar 

  115. Davis, G., Stratman, A., Sacharidou, A., Koh, W.: Molecular basis for endothelial lumen formation and tubulogenesis during vasculogenesis and angiogenic sprouting. Int. Rev. Cell Mol. Biol. 288, 101–165 (2011)

    Google Scholar 

  116. Quaegebeur, A., Segura, I., Carmeliet, P.: Pericytes: blood-brain barrier safeguards against neurodegeneration? Neuron 68(3), 321–323 (2010)

    Google Scholar 

  117. Brooks, P.C., Clark, R.A., Cheresh, D.A.: Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264(5158), 569–571 (1994)

    Google Scholar 

  118. Brooks, P.C., Montgomery, A.M., Rosenfeld, M., Reisfeld, R.A., Hu, T., Klier, G., Cheresh, D.A.: Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79(7), 1157–1164 (1994)

    Google Scholar 

  119. Kim, S., Bell, K., Mousa, S., Varner, J.: Regulation of angiogenesis in vivo by ligation of integrin alpha5-beta1 with the central cell-binding domain of fibronectin. Am. J. Pathol. 156, 1345–1362 (2000)

    Google Scholar 

  120. Ponce, M., Nomizu, M., Kleinman, H.: An angiogenic laminin site and its antagonist bind through the alphav-beta3 and alpha5-beta1 integrins. FASEB J. 15, 1389–1397 (2001)

    Google Scholar 

  121. Stupack, D.G., Cheresh, D.A.: Integrins and angiogenesis. Curr. Top. Dev. Biol. 64, 207–238 (2004)

    Google Scholar 

  122. Ingber, D., Folkman, J.: How does extracellular matrix control capillary morphogenesis? Cell 58, 803–805 (1989)

    Google Scholar 

  123. Deroanne, C.F., Lapiere, C.M., Nusgens, B.V.: In vitro tubulogenesis of endothelial cells by relaxation of the coupling extracellular matrix-cytoskeleton. Cardiovasc. Res. 49(3), 647–658 (2001)

    Google Scholar 

  124. Sieminski, A.L., Hebbel, R.P., Gooch, K.J.: The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro. Exp. Cell Res. 297(2), 574–584 (2004)

    Google Scholar 

  125. Vailhe, B., Lecomte, M., Wiernsperger, N., Tranqui, L.: The formation of tubular structures by endothelial cells is under the control of fibrinolysis and mechanical factors. Angiogenesis 2(4), 331–344 (1998)

    Google Scholar 

  126. Kniazeva, E., Putnam, A.J.: Endothelial cell traction and ECM density influence both capillary morphogenesis and maintenance in 3-D. Am. J. Physiol. Cell Physiol. 297(1), C179–C187 (2009)

    Google Scholar 

  127. Urech, L., Bittermann, A.G., Hubbell, J.A., Hall, H.: Mechanical properties, proteolytic degradability and biological modifications affect angiogenic process extension into native and modified fibrin matrices in vitro. Biomaterials 26(12), 1369–1379 (2005)

    Google Scholar 

  128. Fischer, R.S., Gardel, M., Ma, X., Adelstein, R.S., Waterman, C.M.: Local cortical tension by myosin II guides 3D endothelial cell branching. Current Biol.: CB 19(3), 260–265 (2009)

    Google Scholar 

  129. Mammoto, A., Connor, K.M., Mammoto, T., Yung, C.W., Huh, D., Aderman, C.M., Mostoslavsky, G., Smith, L.E.H., Ingber, D.E.: A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457, 1103–1108 (2009)

    Google Scholar 

  130. Califano, J.P., Reinhart-King, C.A.: The effects of substrate elasticity on endothelial cell network formation and traction force generation. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 3343–3345 (2009)

    Google Scholar 

  131. Kniazeva, E., Putnam, A.: Endothelial cell traction and ECM density influence both capillary morphogenesis and maintenance in 3-D. Am. J. Physiol. Cell Physiol. 297(1), C179–C187 (2009)

    Google Scholar 

  132. Lee, P.F., Yeh, A.T., Bayless, K.J.: Nonlinear optical microscopy reveals invading endothelial cells anisotropically alter three-dimensional collagen matrices. Exp. Cell Res. 315(3), 396–410 (2009)

    Google Scholar 

  133. Krishnan, L., Boying, J., Nguyen, H., Song, H., Weiss, J.: Interaction of angiogenic microvessels with the extracellular matrix. Am. J. Physiol. Heart Circ. Physiol. 293, H3650–H3658 (2007)

    Google Scholar 

  134. Vailhe, B., Ronot, X., Tracqui, P., Usson, Y., Tranqui, L.: In vitro angiogenesis is modulated by the mechanical properties of fibrin gels and is related to alpha(v)beta3 integrin localization. In Vitro Cell. Dev. Biol. Anim. 33, 763–773 (1997)

    Google Scholar 

  135. Vernon, R., Sage, E.: Contraction of fibrillar type I collagen by endothelial cells: a study in vitro. J. Cell. Biochem. 60, 185–197 (1996)

    Google Scholar 

  136. Ghajar, C.M., Blevins, K.S., Hughes, C.C., George, S.C., Putnam, A.J.: Mesenchymal stem cells enhance angiogenesis in mechanically viable prevascularized tissues via early matrix metalloproteinase upregulation. Tissue Eng. 12(10), 2875–2888 (2006)

    Google Scholar 

  137. Kilarski, W.W., Samolov, B., Petersson, L., Kvanta, A., Gerwins, P.: Biomechanical regulation of blood vessel growth during tissue vascularization. Nat. Med. 15(6), 657–664 (2009)

    Google Scholar 

  138. Benest, A.V., Augustin, H.G.: Tension in the vasculature. Nat. Med. 15(6), 608–610 (2009)

    Google Scholar 

  139. Gerwins, P., Skoldenberg, E., Claesson-Welsh, L.: Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis. Crit. Rev. Oncol. Hematol. 34(3), 185–194 (2000)

    Google Scholar 

  140. Spinale, F.G.: Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol. Rev. 87(4), 1285–1342 (2007)

    Google Scholar 

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Acknowledgments

The authors gratefully acknowledge funding from the National Heart, Lung, and Blood Institute (R01-HL-085339) and a CAREER award from the National Science Foundation (CBET-0968216). S.J.G. was supported by a predoctoral fellowship from NIH Cellular Biotechnology Training Grant (T32-GM-008353).

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  1. Department of Biomedical Engineering, University of Michigan, 1101 Beal Ave, Ann Arbor, MI, 48109, USA

    Stephanie J. Grainger & Andrew J. Putnam

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Correspondence to Andrew J. Putnam .

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    Cynthia A. Reinhart-King

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Grainger, S.J., Putnam, A.J. (2013). ECM Remodeling in Angiogenesis. In: Reinhart-King, C. (eds) Mechanical and Chemical Signaling in Angiogenesis. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30856-7_9

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