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Modulation of physiological angiogenesis in skeletal muscle by mechanical forces: Involvement of VEGF and metalloproteinases

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Abstract

Growth factors are involved in physiological angiogenesis in female reproductive organs but their role in capillary growth in skeletal muscles during activity or exercise training is not proven. Evidence suggests that increases in muscle blood flow and accompanying capillary shear stress and/or wall tension, or mechanical stress due to sarcomere length changes during contraction/relaxation cycles are closely linked with angiogenesis. Time-dependent studies of rat muscles in models with increased shear stress (chronic vasodilator treatment with α1 antagonist prazosin), altered sarcomere length (stretch-induced overload with no increase in blood flow), or both (chronic electrical muscle stimulation) showed a similar increase in capillary supply in all models but by different modes of growth. With prazosin, it occurred by intra-luminal splitting of vessels, with stretch by abluminal sprouting, and in stimulated muscles by both methods. Whole muscle matrix metalloproteinase-2 (MMP-2) was elevated during sprouting growth induced by extravascular tensile forces but not during splitting growth induced by shear. Vascular endothelial growth factor (VEGF) protein was elevated at capillary sites in all three models but with different time courses. With shear as the stimulus, the increase occurred early although there was little capillary proliferation; it matched the rise in proliferation in stretched muscles but lagged behind proliferation in stimulated muscles. Mechanical forces therefore influence MMP and VEGF expression and capillary growth patterns in skeletal muscle differentially depending upon whether they act intra- or ab-luminally. In exercise-trained muscles, the type of capillary growth remains to be determined but the most likely stimuli for angiogenesis are increased blood flow and shear forces to vessel supplying the active fibres, probably linked with metabolic factors.

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References

  1. White FC, Bloor CM, McKirnan MD, Carroll SM. Exercise training in swine promotes growth of arteriolar bed and capillary angiogenesis in heart. J Appl Physiol 1998; 85: 1160–8.

    Google Scholar 

  2. Hudlicka O. The response of muscle to enhanced and reduced activity. Baillière’s Clin Endocrin Metab 1990; 4: 417–39.

    Google Scholar 

  3. Hudlicka O, Brown MD, Egginton S. Angiogenesis in skeletal and cardiac muscle. Physiol Rev 1992; 72: 369–417.

    Google Scholar 

  4. Ausprunck DH, Folkman J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 1977; 14: 53–66.

    Google Scholar 

  5. Rhodin J, Fujita H. Capillary growth in the mesentery of normal young rats. Intravital video and electron microscope analysis. J Submicrosc Cytol Pathol 1989; 21: 1–34.

    Google Scholar 

  6. Mignatti P, Rifkin DB. Plasminogen activators and matrix metalloproteinases in angiogenesis. Enzyme Protein 1996; 49: 117–37.

    Google Scholar 

  7. Kliche S, Waltenberger J. VEGF receptor signaling and endothelial function. Iumb Life 2001; 52: 61–6.

    Google Scholar 

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

    Google Scholar 

  9. Burri PH, Tarek MR. A novel mechanism of capillary growth in the rat pulmonary circulation. Anat Rec 1990; 228: 35–45.

    Google Scholar 

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

    Google Scholar 

  11. van Groningen JP, Wenink AVG, Testers LHM. Myocardial capillaries: Increase in number by splitting of vessels. Anat Embryol 1991; 184: 65–70.

    Google Scholar 

  12. Adair TH, Gay WJ, Montani J-P. Growth regulation of the vascular system: Evidence of a metabolic hypothesis. Am J Physiol 1990; 259: R393–404.

    Google Scholar 

  13. Hudlicka O. What makes blood vessels grow? J Physiol 1991; 444: 1–24.

    Google Scholar 

  14. Ando J, Nomura H, Kamiya A. The effect of fluid shear stress on the migration and proliferation of cultured endothelial cells. Microvasc Res 1987; 33: 62–70.

    Google Scholar 

  15. Resnick N, Gimbrone MA Jr. Hemodynamic forces are complex regulators of endothelial gene expression. FASEB J 1995; 9: 874–82.

    Google Scholar 

  16. Tardy Y, Resnick N, Nagel T et al. Shear stress gradients remodel endothelial monolayers in vitro via cell proliferationmigration-loss cycle. Arterio Thromb Vasc Biol 1997; 17: 3102–6.

    Google Scholar 

  17. Lehoux S, Tedgui A. Signal transduction and mechanical stresses in vascular wall. Hypert 1998; 32: 338–45.

    Google Scholar 

  18. Vouyouka AG, Powell RJ, Ricotta J et al. Ambient pulsatile pressure modulates endothelial cell proliferation. J Mol Cell Cardiol 1998; 30: 609–15.

    Google Scholar 

  19. Hudlicka O, Brown MD, Egginton S. The role of hemodynamic and mechanical factors in vascular growth and remodelling. In Lelkes P (ed): Mechanical Forces and the Endothelium. Amsterdam: Harwood Academic Publishers 1999; 291–359.

    Google Scholar 

  20. Adolfsson J. The time dependence of training-induced increase in skeletal muscle capillarization and the spatial capillary to fibre relationship in normal and neovascularized skeletal muscle of rats. Acta Physiol Scand 1986; 128: 259–66.

    Google Scholar 

  21. Andersen R, Henriksson J. Capillary supply of the quadriceps femoris muscle of man: Adaptive response to exercise. J Physiol 1977; 270: 677–90.

    Google Scholar 

  22. Suzuki J, Kobayashi T, Uruma T, Koyama T. Time-course changes in arteriolar and venular portions of capillary in young treadmill-trained rats. Acta Physiol Scand 2001; 171: 77–86.

    Google Scholar 

  23. Ljungqvist A, Unge G. Capillary proliferative activity in myocardium and skeletal muscle of exercised rats. J Appl Physiol 1977; 43: 306–7.

    Google Scholar 

  24. Ogawa Y. On the fine structural changes of the microvascular beds in skeletal muscle. J Yokohama City Univ Ser Sport Sci Med 1977; 6: 1–19.

    Google Scholar 

  25. Appell H-J. Morphological studies on skeletal muscle capillaries under conditions of high altitude training. Int J Sports Med 1980; 1: 103–9.

    Google Scholar 

  26. Schroeder W, Treumann F, Rathscheck W, Muller R. Muscle pO2 in trained and untrained non-anaesthetized guinea pigs and in men. Eur J Appl Physiol 1976; 35: 215–21.

    Google Scholar 

  27. Richardson RS, Noyszeski EA, Kendrick KF et al. Myoglobin O2 desaturation during exercise: Evidence of limited O2 transport. J Clin Invest 1995; 96: 1916–26.

    Google Scholar 

  28. Bockman EL, McKenzie JE. Tissue adenosine content in active soleus and gracilis muscles of cats. Am J Physiol 1983; 244: H552–9.

    Google Scholar 

  29. Meininger CJ, Schelling ME, Granger HJ. Adenosine and hypoxia stimulate proliferation and migration of endothelial cells. Am J Physiol 1988; 255: H554–62.

    Google Scholar 

  30. Ziada AMAR, Hudlicka O, Tyler KR, Wright AJ. The effect of long-term vasodilation on capillary growth and performance in rabbit heart and skeletal muscle. Cardiovasc Res 1984; 18: 724–32.

    Google Scholar 

  31. Breen EC, Johnson EX, Wagner H et al. Angiogenic growth factor mRNA in muscle a single bout of exercise. J Appl Physiol 1996; 81: 355–61.

    Google Scholar 

  32. Gustafsson T, Puntschart A, Kaijser L et al. Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle. Am J Physiol 1999; 276: H679–85.

    Google Scholar 

  33. Richardson RS, Wagner H, Mudaliar SRD et al. Human VEGF gene expression in skeletal muscle: The effect of acute normoxic and hypoxic exercise. Am J Physiol 1999; 277: H2247–52.

    Google Scholar 

  34. Amaral SL, Papanek PE, Greene AS. Angiotensin II and VEGF are involved in angiogenesis induced by short-term exercise training. Am J Physiol 2001; 281: H1163–9.

    Google Scholar 

  35. Gavin TP, Wagner PD. Effect of short-term exercise training on angiogenic growth factor gene responses in rats. J Appl Physiol 2001; 90: 1219–26.

    Google Scholar 

  36. Richardson RS, Wagner H, Mudaliar SRD et al. Exercise adaptation attenuates VEGF gene expression in human skeletal muscle. Am J Physiol 1999; 279: H772–8.

    Google Scholar 

  37. Olfert IM, Breen EC, Mathieu-Costello O, Wagner PD. Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia. J Appl Physiol 2001; 91: 1176–84.

    Google Scholar 

  38. Ingjer F. Effects of endurance training on muscle fibre ATPase activity, capillary supply and mitochondria in man. J Physiol 1979; 294: 419–32.

    Google Scholar 

  39. Laughlin MH, Armstrong RB. Muscle blood flow distribution patterns as a function of running speed in rats. Am J Physiol 1982; 243: H296–306.

    Google Scholar 

  40. Armstrong RB, Laughlin MH. Exercise blood flow patterns within and among rat muscles after training. Am J Physiol 1984; 246: H59–68.

    Google Scholar 

  41. Gute DC, Laughlin MH, Amann JF. Regional distribution of capillary angiogenesis in interval-sprint and low-intensity endurance training. Microcirc 1994; 1: 183–93.

    Google Scholar 

  42. Gute DC, Fraga C, Laughlin MH, Amman JF. Regional changes in capillary supply in skeletal muscle of high-intensity endurancetrained rats. J Appl Physiol 1996; 81: 619–26.

    Google Scholar 

  43. Hudlicka O, Brown MD. Hemodynamic forces, exercise and angiogenesis. In Dormandy JA, Dole WP, Rubanyi GM (eds): Therapeutic Angiogenesis. Berlin: Springer-Verlag 1999; 87–123.

    Google Scholar 

  44. Booth FW, Thomason DB. Molecular and cellular adaptation of muscle in response to exercise: Perspectives of various models. Physiol Rev 1991; 541–85.

  45. Brown MD, Cotter M, Hudlicka O, Vrbova G. The effects of different patterns of muscle activity on capillary density, mechanical properties and structure of slow and fast rabbit muscles. Pflügers Arch 1976; 361: 241–50.

    Google Scholar 

  46. Brown MD, Hudlicka O, Makki RF, Weiss JB. Low-molecularmass-endothelial cell-stimulating angiogenic factor in relation to capillary growth induced in rat skeletal muscle by low-frequency electrical stimulation. Int J Microcirc Clin Exp 1995; 15: 111–6.

    Google Scholar 

  47. Myrhage R, Hudlicka O. Capillary growth in chronically stimulated adult skeletal muscle as studied by intravital microscopy and histological methods in rabbits and rats. Microvasc Res 1978; 16: 73–90.

    Google Scholar 

  48. Pearce SC, Hudlicka O, Brown MD. Effect of indomethacin on capillary growth and microvasculature in chronically stimulated rat skeletal muscles. J Physiol 2000; 526: 435–43.

    Google Scholar 

  49. Hudlicka O, Milkiewicz M, Cotter MA, Brown MD. Hypoxia and expression of VEGF-A protein in relation to capillary growth in electrically stimulated rat and rabbit skeletal muscles. Exp Physiol 2001; 87: 373–81.

    Google Scholar 

  50. Brown MD, Walter H, Hansen-Smith FM et al. Lack of involvement of basic fibroblast growth factor (FGF-2) in capillary growth in skeletal muscles exposed to long-term contractile activity. Angiogenesis 1998; 2: 81–91.

    Google Scholar 

  51. Hang J, Kong L, Gu JW, Adair TH. VEGF gene expression is upregulated in electrically stimulated rat skeletal muscle. Am J Physiol 1995; 269: H1827–31.

    Google Scholar 

  52. Skorjanc D, Jaschinski F, Heine G, Pette D. Sequential increases in capillarization and mitochondrial enzymes in low-frequency stimulated rabbit muscle. Am J Physiol 1998; 274: C810–218.

    Google Scholar 

  53. Annex BH, Torgan CE, Lin P et al. Induction and maintenance of increased VEGF protein by chronic motor nerve stimulation in skeletal muscle. Am J Physiol 1998; 274: H860–7.

    Google Scholar 

  54. Amaral SL, Linderman JR, Morse MM, Greene AS. Angiogenesis induced by electrical stimulation is mediated by angiotensin II and VEGF. Microcirc 2001; 8: 57–67.

    Google Scholar 

  55. Milkiewicz M, Brown MD, Egginton S, Hudlicka O. Association between shear stress, angiogenesis and VEGF in skeletal muscles in vivo. Microcirc 2001; 8: 229–41.

    Google Scholar 

  56. Hudlicka O, Brown MD, Silgram H. Inhibition of capillary growth in chronically stimulated rat muscles by NG-nitro-Larginine (L-NNA), nitric oxide synthase inhibitor. Microvasc Res 2000; 59: 45–51.

    Google Scholar 

  57. Koller A, Kaley G. Shear stress dependent regulation of vascular resistance in health and disease; role of endothelium. Endothelium 1996; 4: 247–72.

    Google Scholar 

  58. Slaaf DW, Oude Egbrink MG. Capillaries and flow distribution play an important role in muscle blood flow reserve capacity. J Mal Vascul 2002; 27: 63–7.

    Google Scholar 

  59. Ellis CG, Mathieu-Costello O, Potter RF et al. Effect of sarcomere length on total capillary length in skeletal muscle: In vivo evidence for longitudinal stretching of capillaries. Microvasc Res 1990; 40: 63–72.

    Google Scholar 

  60. Groom AC, Ellis CG, Potter RF. Microvascular architecture and red cell perfusion in skeletal muscle: Changes during shortening and possible improvement of oxygen transport to tissue. Progr Appl Microcirc 1984; 5: 64–83.

    Google Scholar 

  61. Hudlicka O. Is physiological angiogenesis in skeletal muscle regulated by changes in microcirculation? Microcirc 1998; 5: 7–23.

    Google Scholar 

  62. Ziada AMAR, Hudlicka O, Tyler KR. The effect of long-term administration of a1–blocker prazosin on capillary density in cardiac and skeletal muscle. Pflügers Arch 1989; 415: 355–60.

    Google Scholar 

  63. Fulgenzi G, Graciotti L, Collis MG, Hudlicka O. The effect of alpha1 adrenoceptor antagonist prazosin on capillary supply, blood flow and performance in a rat model of chronic muscle ischaemia. Eur J Endovasc Surg 1998; 16: 71–7.

    Google Scholar 

  64. Ohyanagi M, Faber JE, Nishigaki K. Differential activation of alpha1–and alpha2–adrenoceptors on microvascular smooth muscle during sympathetic nerve stimulation. Circ Res 1991; 68: 232–44.

    Google Scholar 

  65. Marshall JM, Tandon HC. Direct observations of muscle arterioles and venules following contraction of skeletal muscle fibres in the rat. J Physiol 1984; 350: 447–59.

    Google Scholar 

  66. Williams DA, Segal SS. Feed artery role in blood flow control to rat hindlimb skeletal muscles. J Physiol 1993; 463: 631–46.

    Google Scholar 

  67. Egginton S, Hudlicka O, Brown MD et al. Capillary growth in relation to blood flow and performance in overloaded rat skeletal muscle. J Appl Physiol 1998; 856: 2025–32.

    Google Scholar 

  68. Hudlicka O, Brown MD, Cotter M et al. The effect of long-term stimulation of fast muscles on their blood flow, metabolism and ability to withstand fatigue.Pflüger’s Arch 1977; 369: 141–9.

    Google Scholar 

  69. Egginton S, Hudlicka O. Early changes in performance, blood flow and capillary fine structure in rat fast muscles induced by electrical stimulation. J Physiol 1999; 515: 265–75.

    Google Scholar 

  70. Warhol MJ, Siegel AJ, Evans WJ, Silverman LM. Skeletal muscle injury and repair in marathon runners after competition. Am J Pathol 1985; 118: 331–9.

    Google Scholar 

  71. Dawson JM, Hudlicka O. Can changes in microcirculation explain capillary growth in skeletal muscle? Int J Exp Path 1993; 74: 65–71.

    Google Scholar 

  72. Hawker MJ, Egginton S. The effect of stimulation frequency on blood flow in rat fast skeletal muscles. Exp Physiol 1999; 84: 941–6.

    Google Scholar 

  73. Poole DC, Musch TI, Kindig CA. In vivo microvascular structural and functional consequences of muscle length changes. Am J Physiol 1997; 272: H2107–14.

    Google Scholar 

  74. Kinding CA, Poole DC. Sarcomere length-induced alterations of capillary hemodynamics in rat spinotrapezius muscle: Vasoactive vs. passive control. Microvasc Res 2001; 61: 64–5.

    Google Scholar 

  75. Maspers M, Bjornberg J, Mellander S. Relation between capillary pressure and vascular tone over the range from maximum dilation to maximum constriction in cat skeletal muscle. Acta Physiol Scand 1990; 140: 73–83.

    Google Scholar 

  76. Rivilis I, Milkiewicz M, Boyd P et al. Differential involvement of MMP-2 and VEGF during muscle stretch versus shear stressinduced angiogenesis. Am J Physiol 2002; 283: H143–83.

    Google Scholar 

  77. Egginton S, Zhou A-L, Brown MD, Hudlicka O. Unorthodox angiogenesis in skeletal muscle. Cardiovasc Res 2001; 49: 634–46.

    Google Scholar 

  78. Zhou A-L, Egginton S. Immunolabelling of proliferating cells during skeletal muscle angiogenesis. J Vasc Res 1998; 35: 386 (abstract).

    Google Scholar 

  79. Zhou A-L, Egginton S, Hudlicka O, Brown MD. Internal division of capillaries in rat skeletal muscle in response to chronic vasodilator treatment with α1–antagonist prazosin. Cell Tiss Res 1998; 293: 293–303.

    Google Scholar 

  80. Zhou A-L, Egginton S, Brown MD, Hudlicka O. Capillary growth in overloaded, hypertrophic adult rat skeletal muscle: An ultrastructural study. Anat Rec 1998; 252: 49–63.

    Google Scholar 

  81. Hansen-Smith FM, Hudlicka O, Egginton S. In vivo angiogenesis in adult rat skeletal muscle: Early changes in capillary network architecture and ultrastructure. Cell Tiss Res 1996; 286: 123–36.

    Google Scholar 

  82. Hansen-Smith FM. Capillary network patterning during angiogenesis. Clin Exp Pharmacol Physiol 2000; 27: 830–5.

    Google Scholar 

  83. Hiraoka N, Allken E, Apel IJ et al. Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysis. Cell 1998; 95: 365–77.

    Google Scholar 

  84. Lafleur MA, Forsyth PA, Atkinson SJ et al. Perivascular cells regulate endothelial membrane type-1 matrix metalloproteinase activity. Biochem Biophys Res Comm 2001; 282: 463–73.

    Google Scholar 

  85. Stetler-Stevenson WG. Matrix metalloproteinases in angiogenesis: A moving target for therapeutic intervention. J Clin Invest 1999; 103: 1237–41.

    Google Scholar 

  86. Haas TL, Madri JA. Extracellular matrix-driven metalloproteinase production in endothelial cells: Implication for angiogenesis. Trend Cardiovasc Med 1999; 9: 70–7.

    Google Scholar 

  87. Pepper MS. Extracellular proteolysis and angiogenesis. Thromb Haemostas 2001; 86: 346–55.

    Google Scholar 

  88. Nguyen M, Arkell J, Jackson CJ. Human endothelial gelatinases and angiogenesis. Int J Biochem Cell Biol 2001; 33: 960–70.

    Google Scholar 

  89. Jia MC, Schwartz MA, Sang QA. Suppression of human microvascular endothelial cell invasion and morphogenesis with matrixin inhibitors. Adv Exp Med Biol 2000; 476: 181–94.

    Google Scholar 

  90. Abruzzeese TA, Guzman RJ, Martin RL et al. Matrix metalloproteinase inhibition limits arterial enlargement in a rodent arteriovenous fistula model. Surgery 1998; 124: 328–34.

    Google Scholar 

  91. Haas TL, Milkiewicz M, Davis SJ et al. Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle. Am J Physiol 2000; 279: H1540–47.

    Google Scholar 

  92. Haas TL, Davis SJ, Madri JA. Three-dimensional type I collagen lattices induce coordinate expression of matrix metalloproteinases MT1–MMP and MMP-2 in microvascular endothelial cells. J Biol Chem 1998; 273: 3604–10.

    Google Scholar 

  93. Meng X, Mavromatis K, Galis ZS. Mechanical stretching of human saphenous vein grafts induces expression and activation of matrix-degrading enzymes associated with vascular tissue injury and repair. Exp Mol Pathol 1999; 66: 227–37.

    Google Scholar 

  94. Yamaguchi S, Yamaguchi M, Yatsuyanagi E et al. Cyclic strain stimulates early growth response gene product 1–mediated expression of membrane type 1 matrix metalloproteinase in endothelium. Lab Invest 2002; 82: 856–948.

    Google Scholar 

  95. Tyagi Sc, Lewis K, Pikes D et al. Stretch-induced membrane type matrix metalloproteinase and tissue plasminogen activator in cardiac fibroblast cells. J Cell Physiol 1998; 176: 374–82.

    Google Scholar 

  96. Koskinen SO, Hoyhtya M, Turpeenniemi-Hujanen T et al. Serum concentrations of collagen degrading enzymes and their inhibitors after downhill running. Scand J Med Sci Sports 2001; 11: 9–15.

    Google Scholar 

  97. Bassiouny HS, Song RH, Hong XF et al. Flow regulation of 72–kD collagenase IV (MMP-2) after experimental arterial injury. Circ 1998; 98: 157–63.

    Google Scholar 

  98. Patterson MA, Leville CD, Hower CD et al. Shear force regulates matrix metalloproteinase activity in human saphenous vein organ culture. J Surg Res 2001; 95: 67–2.

    Google Scholar 

  99. Van Gieson EJ, Skalak TC. Chronic vasodilation induces matrix metalloproteinase 9 (MMP-9) expression during microvascular remodelling in rat skeletal muscle. Microcirc 2001; 8: 25–31.

    Google Scholar 

  100. Hansen-Smith FM, Egginton S, Hudlicka O. Growth of arterioles in chronically stimulated adult rat skeletal muscle. Microcirc 1998; 5: 49–59.

    Google Scholar 

  101. Hansen-Smith F, Egginton S, Zhou A-L, Hudlicka O. Growth of arterioles precedes that of capillaries in stretch-induced angiogenesis in skeletal muscle. Microvasc Res 2001; 62: 1–14.

    Google Scholar 

  102. Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol 2001; 280: C1358–66.

    Google Scholar 

  103. Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Molec Med 1999; 77: 527–43.

    Google Scholar 

  104. Wang H, Keiser JA. Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle: Role of flt-1. Circ Res 1998; 83: 832–40.

    Google Scholar 

  105. Lamoreaux WJ, Fitzgerald ME, Reiner A et al. Vascular endothelial growth factor increases release of gelatinase A and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro. Microvasc Res 1998; 55: 29–42.

    Google Scholar 

  106. Conklin BS, Zhong DS, Zhao W et al. Shear stress regulates occludin and VEGF expression in porcine arterial endothelial cells. J Surg Res 2002; 102: 13–21.

    Google Scholar 

  107. Gan L, Miocic M, Doroudi R et al. Distinct regulation of vascular endothelial growth factor in intact human conduit vessels exposed to laminar fluid shear stress and pressure. Biochem Biophys Res Comm 2000; 272: 490–6.

    Google Scholar 

  108. Miquerol J, Gerstenstein M, Harpal K et al. Multiple development roles of VEGF suggested by a Lac Z-tagged allele. Dev Biol 1999; 212: 307–22.

    Google Scholar 

  109. Roca J, Gavin TP, Jordan M et al. Angiogenic growth factor mRNA responses to passive and contraction-induced hyperperfusion in skeletal muscle. J Appl Physiol 1998; 85: 1142–9.

    Google Scholar 

  110. Benoit H, Jordan M, Wagner H, Wagner PD. Effect of NO, prostaglandins and adenosine on skeletal muscle angiogenic growth factor gene expression. J Appl Physiol 1999; 86: 1513–8.

    Google Scholar 

  111. Papapetropoulos A, Garcia-Gardena G, Madri JA, Sessa WC. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 1997; 100: 3131–9.

    Google Scholar 

  112. Hood JD, Meininger CJ, Ziche M, Granger HJ. VEGF upregulates ecNOS message, protein and NO production in human endothelial cells. Am J Physiol 1998; 274: H1054–8.

    Google Scholar 

  113. Ziche M, Morbidelli L, Choudhouri R et al. Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 1997; 99: 2625–34.

    Google Scholar 

  114. Gavin TP, Spector DA, Wagner H, Breen EC, Wagner PD. Nitric oxide synthase inhibition attenuates the skeletal muscle VEGF mRNA response to exercise. J Appl Physiol 2000; 88: 1192–8.

    Google Scholar 

  115. Seko Y, Takahashi N, Shibuya M, Yazaki Y. Pulsatile stretch stimulates vascular endothelial growth factor (VEGF) secretion by cultured rat cardiac myocytes. Biochem Biophys Res Comm 1999; 254: 462–5.

    Google Scholar 

  116. Zheng W, Brown MD, Brock TA et al. Bradycardia-induced coronary angiogenesis is dependent on vascular endothelial growth factor. Circ Res 1999; 85: 192–8.

    Google Scholar 

  117. Kim CH, Cho YS, Chun YS et al. Early expression of myocardial HIF-1 alpha in response to mechanical stresses: Regulation by stretch-activated channels and the phosphatidylinositol 3–kinase signalling pathway. Circ Res 2002; 90: E25–33.

    Google Scholar 

  118. Shyu KG, Chang ML, Wang BW et al. Cyclical mechanical stretching increases the expression of vascular endothelial growth factor in rat vascular smooth muscle cells. J Formosan Med Assoc 2001; 100: 741–7.

    Google Scholar 

  119. Quinn TP, Schlueter M, Soifer SJ, Gutierrez JA. Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells. Am J Physiol 2002; 282: L897–903.

    Google Scholar 

  120. Smith JD, Davies N, Willis AL et al. Cyclic stretch induces the expression of vascular endothelial growth factor in vascular smooth muscle cells. Endothelium; J Endo Cell Res 2001; 8: 41–8.

    Google Scholar 

  121. Zheng W, Seftor EA, Meininger CJ et al. Mechanisms of coronary angiogenesis in response to stretch; role of VEGF and TGF-b. Am J Physiol 2001; 280: H909–17.

    Google Scholar 

  122. Deryugina EI, Soroceanu L, Strongin AY. Up-regulation of vascular endothelial growth factor by membrane-type 1 matrix metalloproteinase stimulates human glioma xenograft growth and angiogenesis. Cancer Res 2002; 62: 580–8.

    Google Scholar 

  123. Sounni NE, Devy L, Hajitou A et al. MT1–MMP expression promotes tumour growth and angiogenesis through of vascular endothelial growth factor expression. FASEB J 2002; 16: 555–64.

    Google Scholar 

  124. Brown MD, Milkiewicz M, Hudlicka O. Multiple sources and roles for VEGF in activity-induced angiogenesis in skeletal muscles. J Physiol 2001; 536(P): 12S–13S (Abstract).

    Google Scholar 

  125. Verhaeg J, Milkiewicz M, Brown MD et al. Proliferation of capillaries induced by electrical stimulation in relation to muscle fibre type in rats. J Vasc Res 2001; 38: 409 (Abstract).

    Google Scholar 

  126. Chen BP, Li YS, Zhao Y et al. DNA microarray analysis of gene expression in endothelial cells in response to 24h shear stress. Physiol Genomics 2001; 7: 55–63.

    Google Scholar 

  127. Da Silva-Azevedo L, Baum O, Zakrewicz A, Pries AR. Vascular endothelial growth factor is expressed in endothelial cells isolated from skeletal muscles of nitric oxide synthase knockout mice during prazosin-induced angiogenesis. Biochem Biophys Res Comm 2002; 297: 1270–6.

    Google Scholar 

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  1. School of Sport and Exercise Sciences, University of Birmingham, Birmingham, UK

    M.D. Brown

  2. Department of Physiology, University of Birmingham, Medical School, Birmingham, B15 2TT, UK

    O. Hudlicka

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Brown, M., Hudlicka, O. Modulation of physiological angiogenesis in skeletal muscle by mechanical forces: Involvement of VEGF and metalloproteinases. Angiogenesis 6, 1–14 (2003). https://doi.org/10.1023/A:1025809808697

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