Cell Biochemistry and Biophysics

, Volume 43, Issue 1, pp 1–15 | Cite as

The art of arteriogenesis

Original Article


The identification of collateral artery growth (arteriogenesis) as the only mechanism to compensate for the loss of an occluded artery forced us to define the mechanisms responsible for this type of vessel growth. To achieve this, a variety of coronary as well as peripheral models of arteriogenesis have been developed. Based on these studies it is obvious that arteriogenesis obeys different mechanisms than angiogenesis, the sprouting of capillaries. Upon occlusion of an artery, the blood flow is redirected into preexisting arteriolar anastomoses that experience increased mechanical forces such as shear stress and circum ferential wall stress. The endothelium of the arteriolar connections is then activated, resulting in an increased release of monocyte-attracting proteins as well as an upregulation of adhesion molecules. Upon adherence and extravasation, monocytes promote arteriogenesis by supplying growth factors and cytokines that bind to receptors that are expressed on vascular cells within a limited time frame. Animal studies evidenced that factors, such as monocyte chemoattractant protein-1, granulocyte-monocyte colony-stimulating factor, or transforming growth factor-β1, that either attract or prolong the lifetime of monocytes efficiently enhance collateral artery growth, an effect that was seen only to a minor degree after application of a single growth factor. Bone marrow-derived stems cells and endothelial progenitor cells do not incorporate in growing arteries but, rather, function as supporting cells. Complete elucidation of the mechanisms of arteriogenesis may lead to efficacious therapies counteracting the devastating consequences of vascular occlusive diseases.

Index Entries

Arteriogenesis collateral arteries monocytes mechanical forces hypoxia stem cells vascular endothelial growth factor fibroblast growth factor urokinase plasminogen activator cofilin 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Schaper, W., DeBrabander, M., and Lewi, P. (1971) DNA-synthesis and mitoses in coronary collateral vessels of the dog. Circ. Res. 28, 671–679.PubMedGoogle Scholar
  2. 2.
    Wolf, C., Cai, J. W., Vosschulte, R., et al. (1998) Vascular remodeling and altered protein expression during growth of coronary collateral arteries. J. Mol. Cell. Cardiol. 30, 2291–2305.PubMedCrossRefGoogle Scholar
  3. 3.
    Scholz, D., Ziegelhoeffer, T., Helisch, A., et al. (2002) Contribution of arteriogenesis and angiogenesis to postocclusive hindlimb perfusion in mice. J. Mol. Cell. Cardiol. 34, 775–787.PubMedCrossRefGoogle Scholar
  4. 4.
    Herzog, S., Sager, H., Khmelevski, E., Deylig, A., and Ito, W. D. (2002) Collateral arteries grow from preexisting anastomoses in the rat hindlimb. Am. J. Physiol. Heart Circ. Physiol. 283, H2012-H2020.PubMedGoogle Scholar
  5. 5.
    Ito, W. D., Arras, M., Winkler, B., Scholz, D., Schaper, J., and Schaper, W. (1997) Monocyte chemotactic protein-1 increases collateral and peripheral conductance after femoral artery occlusion. Circ. Res. 80, 829–837.PubMedGoogle Scholar
  6. 6.
    Schaper, W., Pipp, F., Scholz, D., et al. (2004) Physical forces and their translation into molecular mechanisms, in Arteriogenesis, (Schaper, W. and Schaper, J. eds.) Kluwer Academic, Boston, pp. 73–114.CrossRefGoogle Scholar
  7. 7.
    Neufeld, G., Cohen, T., Gengrinovitch, S., and Poltorak, Z. (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13, 9–22.PubMedGoogle Scholar
  8. 8.
    Fulton, W. F. M. (1965) The Coronary Arteries, Charles C. Thomas., Springfield, IL.Google Scholar
  9. 9.
    Schaper, W. and Schaper, J. (1993) Collateral Circulation—Heart, Brain, Kidney, Limbs. Kluwer Academic, Boston.Google Scholar
  10. 10.
    Paskins-Hurlburt, A. and Hollenberg, N. K. (1992) “Tissue need” and limb collateral arterial growth: skeletal contractile power and perfusion during collateral development in the rat. Circ. Res. 70, 546–553.PubMedGoogle Scholar
  11. 11.
    Henry, T. D., Annex, B. H., McKendall, G. R., et al. (2003) The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation 107, 1359–1365.PubMedCrossRefGoogle Scholar
  12. 12.
    Makinen, K., Manninen, H., Hedman, M., et al. (2002) Increased vascularity detected by digital substraction angiography after VEGF gene transfer to human lower limb artery: a randomized., placebo-controlled, double-blinded phase II study. Mol. Ther. 6, 127–133.PubMedCrossRefGoogle Scholar
  13. 13.
    Rajagopalan, S., Mohler, E. R., 3rd., Lederman, R. J., et al. (2003) Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication. Circulation 108, 1933–1938.PubMedCrossRefGoogle Scholar
  14. 14.
    Kastrup, J. (2003) Therapeutic angiogenesis in ischemic heart disease: gene or recombinant vascular growth factor protein therapy? Curr. Gene Ther. 3, 197–206.PubMedCrossRefGoogle Scholar
  15. 15.
    Lee, C. W., Stabile, E., Kinnaird, T., et al. (2004) Temporal patterns of gene expression after acute hindlimb ischemia in mice: insights into the genomic program for collateral vessel development. J. Am. Coll. Cardiol. 43, 474–482.PubMedCrossRefGoogle Scholar
  16. 16.
    Ito, W. D., Arras, M., Scholz, D., Winkler, B., Htun, P., and Schaper, W. (1997) Angiogenesis but not collateral growth is associated with ischemia after femoral artery occlusion. Am. J. Physiol. 273, H1255-H1265.PubMedGoogle Scholar
  17. 17.
    Deindl, E. and Schaper, W. (1999) Collateral and capillary formation—a comparison, in Therapeutic Angiogenesis, Ernst Schering Research Foundation—Workshop 28 (Dormandy, J. A., Dole, W. P., and Rubanyi, G. M., eds.), Springer, Berlin, pp. 67–86.Google Scholar
  18. 18.
    Deindl, E., Buschmann, I., Hoefer, I. E., et al. (2001) Role of ischemia and hypoxia-inducible genes in arteriogenesis after femoral artery occlusion in the rabbit. Circ. Res. 89, 779–786.PubMedCrossRefGoogle Scholar
  19. 19.
    Deindl, E., Helisch, A., Scholz, D., Heil, M., Wagner, S., and Schaper, W. (2004) Role of hypoxia/ischemia/VEGF-A and strain differences, in Arteriogenesis, (Schaper, W. and Schaper, J., eds.) Kluwer Academic, Boston, pp. 115–130.CrossRefGoogle Scholar
  20. 20.
    Scholz, D., Ito, W., Fleming, I., Deindl, E., Sauer, A., Wiesnet, M., Busse, R., Schaper, J., and Schaper, W. (2000) Ultrastructure and molecular histology of rabbit hindlimb collateral artery growth (arteriogenesis). Virchows Arch. 436, 257–270.PubMedCrossRefGoogle Scholar
  21. 21.
    Arras, M., Ito, W. D., Scholz, D., Winkler, B., Schaper, J., and Schaper, W. (1998) Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb. J. Clin. Invest. 101, 41–50.Google Scholar
  22. 22.
    Ziegelhoeffer, T., Fernandez, B., Kostin, S., et al. (2004) Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ. Res. 94, 230–238.PubMedCrossRefGoogle Scholar
  23. 23.
    Busse, R. and Fleming, I. (2003) Regulation of endothelium-derived vasoactive autacoid production by hemodynamic forces. Trends Pharmacol. Sci. 24, 24–29.PubMedCrossRefGoogle Scholar
  24. 24.
    Galbraith, C. G., Skalak, R., and Chien, S. (1998) Shear stress induces spatial reorganization of the endothelial cell cytoskeleton. Cell. Motil. Cytoskel. 40, 317–330.CrossRefGoogle Scholar
  25. 25.
    Moon, A. and Drubin, D. G. (1995) The ADF/cofilin proteins: stimulus-responsive modulators of actin dynamics. Mol. Biol. Cell. 6, 1423–1431.PubMedGoogle Scholar
  26. 26.
    Theriot, J. A. (1997) Accelerating on a treadmill: ADF/cofilin promotes rapid actin turnover in the dynamic cytoskeleton. J. Cell Biol. 136, 1165–1168.PubMedCrossRefGoogle Scholar
  27. 27.
    Yonezawa, N., Nishida, E., and Sakai, H. (1985) pH control of actin polymerization by cofilin. J. Biol. Chem. 260, 14,410–14,412.Google Scholar
  28. 28.
    Toshima, J., Toshima, J. Y., Amano, T., Yang, N., Narumiya, S., and Mizundo, K. (2001) Cofilin phosphorylation by protein kinase testicular protein kinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation. Mol. Biol. Cell 12, 1131–1145.PubMedGoogle Scholar
  29. 29.
    Arber, S., Barbayannis, F. A., Hanser, H., et al. (1998) Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 393, 805–809.PubMedCrossRefGoogle Scholar
  30. 30.
    Niwa, R., Nagata-Ohashi, K., Takeichi, M., Mizundo, K., and Uemura, T. (2002) Control of actin reorganization by slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell 108, 233–246.PubMedCrossRefGoogle Scholar
  31. 31.
    Ono, S., Minami, N., Abe, H., and Obinata, T. (1994) Characterization of a novel cofilin isoform that is predominantely expressed in mammilian skeletal muscle. J. Biol. Chem. 269, 15,280–15,286.Google Scholar
  32. 32.
    Boengler, K., Pipp, F., Broich, K., Fernandez, B., Schaper, W., and Deindl, E. (2003) Identification of differentially expressed genes like cofilin2 in growing collateral arteries. Biochem. Biophys. Res. Commun. 17, 751–756.CrossRefGoogle Scholar
  33. 33.
    Vartiainen, M. K., Mustonen, T., Mattila, P. K., et al. (2002) The three mouse actin-depolymerizing factor/cofilins evolved to fullfill cell-type-specific requirements for actin dynamics. Mol. Biol. Cell 13, 725–732.CrossRefGoogle Scholar
  34. 34.
    Baird, A. and Klagsbrunn, M. (1991) The fibroblast growth factor family. Cancer Cells 3, 239–243.PubMedGoogle Scholar
  35. 35.
    Fernig, D. G. and Gallagher, J. T. (1994) Fibroblast growth factors and their receptors: an information network controlling tissue growth, morphogenesis and repair. Prog. Growth Factor Res. 5, 353–377.PubMedCrossRefGoogle Scholar
  36. 36.
    Givol, D. and Yayon, A. (1992) Complexity of FGF receptors: genetic basis for structural diversity and functional specificity. FASEB J. 6, 3362–3369.PubMedGoogle Scholar
  37. 37.
    Partanen, J., Vainikka, S., Korhonen, J., Armstrong, E., and Alitalo, K. (1992) Diverse receptors for fibroblast growth factors. Prog. Growth Factors Res. 4, 69–83.CrossRefGoogle Scholar
  38. 38.
    Schumacher, B., Pecher, P., von Specht, B. U., and Stegmann, T. (1998) Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heart disease. Circulation 97, 645–650.PubMedGoogle Scholar
  39. 39.
    Unger, E. F., Banai, S., Shou, M., et al. (1994) Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. Am. J. Physiol. 266, H1588-H1595.PubMedGoogle Scholar
  40. 40.
    Yang, H. T., Deschenes, M. R., Ogilvie, R. W., and Terjung, R. L. (1996) Basic fibroblast growth factor increases collateral blood flow in rats with femoral arterial ligation. Circ. Res. 79, 62–69.PubMedGoogle Scholar
  41. 41.
    Rajanayagam, M. A., Shou, M., Thirumurti, V., et al. (2000) Intracoronary basic fibroblast growth factor enhances myocardial collateral perfusion in dog. J. Am. Coll. Cardiol. 35, 519–526.PubMedCrossRefGoogle Scholar
  42. 42.
    Horvath, K. A., Doukas, J., Lu, CY., et al. (2002) Myocardial function recovery after fibroblast growth factor 2 gene therapy as assessed by echocardiography and magnetic resonance imaging. Ann. Thorac. Surg. 74, 481–486.PubMedCrossRefGoogle Scholar
  43. 43.
    Simons, M., Annex, B. H., Laham, R. J., et al. (2002) Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial. Circulation 105, 788–793.PubMedCrossRefGoogle Scholar
  44. 44.
    Lederman, R. J., Mendelsohn, F. O., Anderson, R. D., et al. (2002) Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial. Lancet 359, 2053–2058.PubMedCrossRefGoogle Scholar
  45. 45.
    Burgess, W. H. and Maciag, T. (1989) The heparin-binding (fibroblast) growth factor family of proteins. Annu. Rev. Biochem. 58, 575–606.PubMedCrossRefGoogle Scholar
  46. 46.
    Basilico, C. and Moscatelli, D. (1992) The FGF family of growth factors and oncogenes. Adv. Cancer Res. 59, 115–165.PubMedGoogle Scholar
  47. 47.
    Johnson, D. E. and Williams, L. T. (1993) Structural and functional diversity in the FGF receptor multigene family growth factors and oncogenes. Adv. Cancer Res. 60, 1–60.PubMedGoogle Scholar
  48. 48.
    Jin, Y., Pasumarthi, B. S., Bock, M. E., Lytras, A., Kardami, E., and Cattini, P. A. (1994) Cloning and expression of fibroblast growth factor receptor-1 isoforms in the mouse heart: evidence for isoform switching during heart development. J. Mol. Cell. Cardiol. 26, 1449–1459.PubMedCrossRefGoogle Scholar
  49. 49.
    Wang, J.-K., Gao, G., and Goldfarb, M. (1994) Fibroblast growth factor receptors have different signaling and mitogenic potentials. Mol. Cell. Biol. 14, 181–188.PubMedGoogle Scholar
  50. 50.
    Abraham, J. A., Mergia, A., Whang, J. L., Tumola, A., Gospodarowicz, D., and Fiddes, J. C. (1986) Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science 233, 545–548.PubMedCrossRefGoogle Scholar
  51. 51.
    Muthukrishan, L., Warder, E., and McNeil, P. L. (1991) Basic fibroblast growth factor is efficiently released from cytosolic storage sites through plasma membrane disruptions of endothelial cells. J. Cell. Physiol. 148, 1–16.CrossRefGoogle Scholar
  52. 52.
    McNeil, P. L., Muthukrishnan, W. E., and D'Amore, P. A. (1989) Growth factors are released by mechanically wounded endothelial cells. J. Cell Biol. 109, 811–821.PubMedCrossRefGoogle Scholar
  53. 53.
    Mignatti, P., Morimoto, T., and Rifkin, D. B. (1992) Basic fibroblast growth factor, a protein devoid of of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex. J. Cell. Physiol. 151, 81–93.PubMedCrossRefGoogle Scholar
  54. 54.
    Gloe, T., Sohn, H. Y., Meininger, G. A., and Pohl, U. (2002) Shear stress-induced release of basic fibroblast growth factor from endothelial cells is mediated by matrix interaction via Integrin αvβ3. J. Biol. Chem. 277, 23,453–23,458.CrossRefGoogle Scholar
  55. 55.
    Prudovsky, I., Bagala, C., Tarantini, F., Mandinova, A., Bellum, S., and Maciag, T. (2002) The intracellular translocation of the components of the fibroblast growth factor 1 release complex precedes their assembly prior to export. J. Cell Biol. 158, 201–208.PubMedCrossRefGoogle Scholar
  56. 56.
    Schlessinger, J. and Ullrich, A. (1992) Growth factor signaling by receptor tyrosine kinases. Neuron 9, 383–391.PubMedCrossRefGoogle Scholar
  57. 57.
    Schlessinger, J., Lax, I., and Lemmon, M. (1995) Regulation of growth factor activation by proteoglycans: what is the role of the low affinity receptors? Cell 83, 357–360.PubMedCrossRefGoogle Scholar
  58. 58.
    Friesel, R., and Maciag, T. (1999) Fibroblast growth factor prototype release and fibroblast growth factor receptor signaling. Thromb. Haemost. 82, 748–754.PubMedGoogle Scholar
  59. 59.
    Liekens, S., Neyts, J., Degréve, B., and De Clercq, E., (1997) The sulfonic acid polymers PAMPS [Poly(2-Acrylamido-2-Methyl-1-Propanesulfonoc Acid] and related analogons are highly potent inhibitors of angiogenesis. Oncol. Res. 9, 173–181.PubMedGoogle Scholar
  60. 60.
    Deindl, E., Hoefer, I. E., Fernandez, B., Barancik, M., Heil, M., Strniskova, M., and Schaper, W. (2003) Involvement of the fibroblast growth factor system in adaptive and chemokine-induced arteriogenesis. Circ. Res. 92, 561–568.PubMedCrossRefGoogle Scholar
  61. 61.
    Deindl, E., Fernandez, B., Ziegelhoeffer, T., and Schaper, W. (2001) Collateral artery growth is associated with an increased expression of Egr-1. FASEB J. 15, A1079Google Scholar
  62. 62.
    Vogel, S., Kubin, T., Barancik, M., Deindl, E., von der Ahe, D., and Zimmermann, R. (2004) Signal transduction pathways in smooth muscle cells involved in arteriogenesis, in Arteriogenesis, (Schaper, W. and Schaper, J., eds.) Kluwer Academic, Boston, pp. 213–232.CrossRefGoogle Scholar
  63. 63.
    Schwachtgen, J. L., Houston, P., Campbell, C., Sukhatme, V., and Braddock, M. (1998) Fluid shear stress activation of erg-1 transcription in cultured human endothelial and epithelial cells is mediated via the extracellular signalrelated kinase 1/2 mitogen-activated protein kinase pathway. J. Clin. Invest. 101, 2540–2549.PubMedGoogle Scholar
  64. 64.
    Collen, D. and Lijnen, H. R. (1991) Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 78, 3114–3124.PubMedGoogle Scholar
  65. 65.
    Vassalli, J. D. (1994) The urokinase receptor. Fibrinolysis, 8, 172–181.CrossRefGoogle Scholar
  66. 66.
    Carmeliet, P. and Collen, D. (1996) Gene manipulation and transfer of the plasminogen system and coagulation system in mice. Semin. Thromb. Hemost. 22, 525–542.PubMedCrossRefGoogle Scholar
  67. 67.
    Blasi, F., Conese, M., Moller, L. B., et al. (1994) The urokinase receptor: structure, regulation and inhibitor-mediated internalization. Fibrinolysis 8, 182–188.CrossRefGoogle Scholar
  68. 68.
    Behrendt, N., Ronne, E., and Dano, K. (1995) The structure and function of the urokinase receptor, a membrane protein governing plasminogen activation on the cell surface. Biol. Chem. Hoppe Seyler 376, 269–279.PubMedGoogle Scholar
  69. 69.
    Gyetko, M. R., Todd, R. F. I., Wilkinson, C. C., and Sitrin, R. G. (1994) The urokinase receptor is required for human monocyte chemotaxis in vitro. J. Clin. Invest. 93, 1380–1387.PubMedGoogle Scholar
  70. 70.
    Sitrin, R. G., Todd, R. F., Albrecht, E., and Gyetko, M. R. (1996) The urokinase receptor (CD87) facilitates CD11b/CD18-mediated adhesion of human monocytes. J. Clin. Invest. 97, 1942–1951.PubMedCrossRefGoogle Scholar
  71. 71.
    Waltz D. A., Sailor, L. Z., and Chapman, H. A. (1993) Cytokines induce urokinase-dependent adhesion of human myeloid cells: a regulatory role for plasminogen activator inhibitors. J. Clin. Invest. 91, 1541–1552.PubMedGoogle Scholar
  72. 72.
    Rao, N. K., Shi, G. P., and Chapman, H. A. (1995) Urokinase receptor is a multifunctional protein: influence of receptor occupancy on macrophage gene expression. J. Clin. Invest. 96, 464–474.Google Scholar
  73. 73.
    Sitrin, R. G., Shollenberger, S. B., Strieter, R. M., and Gyetko, M. R. (1996) Endogenously produced urokinase amplifies tumor necrosis factor-secretion by THP-1 mononuclear phagocytes. J. Leukoc. Biol. 59, 302–311.PubMedGoogle Scholar
  74. 74.
    Cao, D., Mizukami, I. F., Garni-Wagner, B. A., et al. (1995) Human urokinase-type plasminogen activator primes neutrophils for superoxide anion release. J. Immunol., 154, 1817–1829.PubMedGoogle Scholar
  75. 75.
    Cai, W. J., Koltai, S., Kocsis, E., et al. (2003) Remodeling of the adventitia during coronary arteriogenesis. Am. J. Physiol. Heart Circ. Physiol. 284, H31-H40.PubMedGoogle Scholar
  76. 76.
    Deindl, E., Ziegelhoffer, T., Kanse, S. M., et al. (2003) Receptor-independent role of the urokinase-type plasminogen activator during arteriogenesis. FASEB J. 17, 1174–1176.PubMedGoogle Scholar
  77. 77.
    Carmeliet, P., Moons, L., Herbert, J.-M., et al. (1997) Urokinase-type but not tissue-type plasminogen activator mediates arterial neointima formation in mice. Circ. Res. 81, 829–839.PubMedGoogle Scholar
  78. 78.
    Syrovets, T., Rohwedder, A., Werchau, H., and Simmet, T. (1997) Plasmin triggers proinflammtory stimulation of human peripheral monocytes including cytokine expression. Naunyn Schmiedebergs Arch. Pharmacol. 312.Google Scholar
  79. 79.
    van Roven, N., Hoefer, I., Buschmann, I., et al. (2002) Exogenous application of transforming growth factor beta 1 stimulates arteriogenesis in the peripheral circulation. FASEB J. 16, 432–434.Google Scholar
  80. 80.
    Buschmann, I. R., Hoefer, I. E., van Royen, N., Katzer, E., Braun-Dulleaus, R., Heil, M., Kostin, S., Bode, C., and Schaper, W. (2001) GM-CSF: a strong arteriogenic factor acting by amplification of monocyte function. Atherosclerosis 159, 343–356.PubMedCrossRefGoogle Scholar
  81. 81.
    Seiler, C., Pohl, T., Wustmann, K., Hutter, D., Nicolet, P. A., Windecker, S., Eberli, F. R., and Meier, B. (2001) Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease: a randomized, double-blind, placebo-controlled study. Circulation 23, 2012–2017.CrossRefGoogle Scholar
  82. 82.
    Heil, M., Ziegelhoeffer, T., Wagner, S., Fernandez, B., Helisch, A., Martin, S., Tribulova, S., Kuziel, W. A., Bachmann, G., and Schaper, W. (2004) Collateral artery growth (arteriogenesis) after experimental arterial occlusion is impaired in mice lacking CC-chemokine receptor-2. Circ. Res. 94, 671–677.PubMedCrossRefGoogle Scholar
  83. 83.
    Hoefer, I. E., van Royen, N., Rectenwald, J. E., et al. (2004) Arteriogenesis proceeds via ICAM-1/Mac-1-mediated mechanisms. Circ. Res. 94, 1179–1185.PubMedCrossRefGoogle Scholar
  84. 84.
    van Roven, N., Voskuil, M., Hoefer, I., et al. (2004) CD44 regulates arteriogenesis in mice and is differentially expressed in patients with poor and good collateralization. Circulation 109, 1647–1652.CrossRefGoogle Scholar
  85. 85.
    Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., and Isner, J. M. (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275, 964–967.PubMedCrossRefGoogle Scholar
  86. 86.
    Shi, Q., Rafii, S., Wu, M. H., et al. (1998) Evidence for circulating bone marrow-derived endothelial cells. Blood 92, 362–367.PubMedGoogle Scholar
  87. 87.
    Orlic, D., Kajstura, J., Chimenti, S., et al. (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc. Natl. Acad. Sci. USA 98, 10,344–10,349CrossRefGoogle Scholar
  88. 88.
    Kalka, C., Masuda, H., Takahashi, T., et al. (2000) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc. Natl. Acad. Sci. USA 97, 3422–3427.PubMedCrossRefGoogle Scholar
  89. 89.
    Orlic, D., Kajstura, J., Chimenti, S., Bodine, D. M., Leri, A., and Anversa, P. (2001) Transplanted adult bone marrow cells repair myocardial infarcts in mice. Ann. NY Acad. Sci. 938, 221–229.PubMedCrossRefGoogle Scholar
  90. 90.
    Kocher, A. A., Schuster, M. D., Szabolcs, M. J., et al. (2001) Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat. Med. 7, 430–436.PubMedCrossRefGoogle Scholar
  91. 91.
    Shintani, S., Murohara T., Ikeda H., et al. (2001) Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation 103, 897–903.PubMedCrossRefGoogle Scholar
  92. 92.
    Kawamoto, A., Gwon, H. C., Iwaguro, H., et al. (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 103, 634–637.PubMedGoogle Scholar
  93. 93.
    Balsam, L. B., Wagers, A. J., Christensen, J. L., Kofidis, T., Weissman, I. L., and Robbins, R. C. (2004) Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428, 668–673.PubMedCrossRefGoogle Scholar
  94. 94.
    Voswinckel, R., Ziegelhoeffer, T., Heil, M., et al. (2003) Circulating vascular progenitor cells do not contribute to compensatory lung growth. Circ. Res. 93, 372–379.PubMedCrossRefGoogle Scholar
  95. 95.
    Beck, H., Voswinckel, R., Wagner, S., et al. (2003) Participation of bone marrow-derived cells in long-term repair processes after experimental stroke. J. Cereb. Blood Flow Metab. 23, 709–717.PubMedCrossRefGoogle Scholar
  96. 96.
    Castro, R. F., Jackson, K. A., Goodell, M. A., Robertson, C. S., Liu, H., and Shine, H. D. (2002) Failure of bone marrow cells to transdifferentiate into neural cells in vivo. Science 297, 1299.PubMedCrossRefGoogle Scholar
  97. 97.
    Wagers, A. J., Sherwood, R. I., Christensen, J. L., and Weissman, I. L. (2002) Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297, 2256–2259.PubMedCrossRefGoogle Scholar
  98. 98.
    Rehman, J., Li, J., Orschell, C. M., and March, K. L. (2003) Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 107, 1164–1169.PubMedCrossRefGoogle Scholar
  99. 99.
    Kinnaird, T., Stabile, E., Burnett, M. S., et al. (2004) Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109, 1543–1549.PubMedCrossRefGoogle Scholar
  100. 100.
    Boengler, K., Pipp, F., Fernandez, B., Ziegelhoeffer, T., Schaper, W., and Deindl, E. (2003) Arteriogenesis is associated with an induction of the cardiac ankyrin repeat protein (carp). Cardiovasc. Res. 59, 573–581.PubMedCrossRefGoogle Scholar
  101. 101.
    Zimmermann, R., Boengler, K., Kampmann, A., et al. (2004) Expression profiling of growing arteries/hunting for new genes involved in arteriogenesis, in Arteriogenesis, (Schaper, W. and Schaper, J., eds.) Kluwer Academic, Boston, pp. 233–252.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  1. 1.Klinikum Grosshadern, Medical Clinic 1Ludwig-Maximilians-UniversityMunichGermany
  2. 2.Department of Experimental CardiologyMax-Planck-Institute for Physiological and Clinical ResearchBad NauheimGermany

Personalised recommendations