Skip to main content
SpringerLink
Log in

Biochemical Mechanisms of Exercise-Induced Angiogenesis

  • Chapter
  • First Online:
Biochemical Basis and Therapeutic Implications of Angiogenesis

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 6))

Abstract

Angiogenesis refers to the growth of new capillaries from a pre-existing capillary bed which can occur during normal physiological and pathological conditions by sprouting and non-sprouting processes, which are activated by different stimuli. Various studies have demonstrated that exercise increases the expression of several growth factors for both sprouting and non-sprouting angiogenesis, including vascular endothelial growth factor and other cytokines in skeletal and cardiac muscle, which are associated with an increase in the number of capillaries in the heart and skeletal muscle. Exercise is known to stimulate the release of several pro- and anti-angiogenic proteins and transcription factors and it appears that hypoxia and/or ischemia play a major role in the growth and expansion of new capillaries and has also been suggested that mechanical forces, such as shear stress or muscle overload, stimulate exercise-induced angiogenesis. More importantly, an in-depth understanding of the factors that influence exercise-induced angiogenesis may contribute to the development of potential therapeutic strategies for the treatment of different diseases including hypertension and ischemic heart disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 179.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9:653–660

    Article  PubMed  CAS  Google Scholar 

  2. Krogh A (1919) The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue. J Physiol 52:409–415

    PubMed  CAS  Google Scholar 

  3. Krogh A (1919) The rate of diffusion of gases through animal tissues, with some remarks on the coefficient of invasion. J Physiol 52:391–408

    PubMed  CAS  Google Scholar 

  4. Krogh A (1919) The supply of oxygen to the tissues and the regulation of the capillary circulation. J Physiol 52:457–474

    PubMed  CAS  Google Scholar 

  5. Krogh A (1922) The anatomy and physiology of capillaries. Yale University Press, New Haven, CT

    Google Scholar 

  6. Hertig A (1935) Angiogenesis in the early human chorion and in the primary placenta of the macaque monkey. Contrib Embryol 25:37–81

    Google Scholar 

  7. Sandison JC (1932) Contraction of blood vessels and observations on the circulation in the transparent chamber in the rabbit’s ear. Anat Rec 24:105–127

    Article  Google Scholar 

  8. Findlay JK (1986) Angiogenesis in reproductive tissues. J Endocrinol 111:357–366

    Article  PubMed  CAS  Google Scholar 

  9. Hudlicka O, Wright AJ, Ziada AM (1986) Angiogenesis in the heart and skeletal muscle. Can J Cardiol 2:120–123

    PubMed  CAS  Google Scholar 

  10. Kawamata T, Speliotes EK, Finklestein SP (1997) The role of polypeptide growth factors in recovery from stroke. Adv Neurol 73:377–382

    PubMed  CAS  Google Scholar 

  11. Kumar S, West D, Shahabuddin S et al (1983) Angiogenesis factor from human myocardial infarcts. Lancet 13:364–368

    Article  Google Scholar 

  12. Burgos H, Herd A, Bennett JP (1989) Placental angiogenic and growth factors in the treatment of chronic varicose ulcers: preliminary communication. J R Soc Med 82:598–599

    PubMed  CAS  Google Scholar 

  13. Baird A (1994) Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factors. Curr Opin Neurobiol 4:78–86

    Article  PubMed  CAS  Google Scholar 

  14. Folkman J, Merler E, Abernathy C et al (1971) Isolation of a tumor factor responsible for angiogenesis. J Exp Med 1:275–288

    Article  Google Scholar 

  15. Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31

    Article  PubMed  CAS  Google Scholar 

  16. Christou H, Yoshida A, Arthur V et al (1998) Increased vascular endothelial growth factor production in the lungs of rats with hypoxia-induced pulmonary hypertension. Am J Respir Cell Mol Biol 18:768–776

    PubMed  CAS  Google Scholar 

  17. Patz A (1978) Current concepts in ophthalmology. Retinal vascular diseases. N Engl J Med 298:1451–1454

    Article  PubMed  CAS  Google Scholar 

  18. Laughlin MH, Bowles DK, Duncker DJ (2012) The coronary circulation in exercise training. Am J Physiol Heart Circ Physiol 302:H10–H23

    Article  PubMed  CAS  Google Scholar 

  19. Savard R, Smith LJ, Palmer JE et al (1988) Site specific effects of acute exercise on muscle and adipose tissue metabolism in sedentary female rats. Physiol Behav 43:65–71

    Article  PubMed  CAS  Google Scholar 

  20. Dohm GL, Huston RL, Askew EW et al (1973) Effects of exercise, training, and diet on muscle citric acid cycle enzyme activity. Can J Biochem 51:849–854

    Article  PubMed  CAS  Google Scholar 

  21. Egginton S (2009) Invited review: activity-induced angiogenesis. Pflugers Arch 457:963–977

    Article  PubMed  CAS  Google Scholar 

  22. Hudlicka O, Brown M, Egginton S (1992) Angiogenesis in skeletal and cardiac muscle. Physiol Rev 72:369–417

    PubMed  CAS  Google Scholar 

  23. Sundberg CJ, Kaijser L (1992) Effects of graded restriction of perfusion on circulation and metabolism in the working leg; quantification of a human ischaemia-model. Acta Physiol Scand 146:1–9

    Article  PubMed  CAS  Google Scholar 

  24. Milkiewicz M, Ispanovic E, Doyle JL et al (2006) Regulators of angiogenesis and strategies for their therapeutic manipulation. Int J Biochem Cell Biol 38:333–357

    Article  PubMed  CAS  Google Scholar 

  25. Dvorak HF, Orenstein NS, Carvalho AC et al (1979) Induction of a fibrin-gel investment: an early event in line 10 hepatocarcinoma growth mediated by tumor-secreted products. J Immunol 122:166–174

    PubMed  CAS  Google Scholar 

  26. Dvorak HF, Brown LF, Detmar M et al (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029–1039

    PubMed  CAS  Google Scholar 

  27. Gustafsson T, Puntschart A, Kaijser L et al (1999) Exercise-induced expression of angiogenesis-­related transcription and growth factors in human skeletal muscle. Am J Physiol 276:H679–H685

    PubMed  CAS  Google Scholar 

  28. Richardson RS, Wagner H, Mudaliar SR et al (1999) Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise. Am J Physiol 277:H2247–H2252

    PubMed  CAS  Google Scholar 

  29. Gustafsson T, Knutsson A, Puntschart A et al (2002) Increased expression of vascular endothelial growth factor in human skeletal muscle in response to short-term one-legged exercise training. Pflugers Arch 444:752–759

    Article  PubMed  CAS  Google Scholar 

  30. Gavin TP, Robinson CB, Yeager RC et al (2004) Angiogenic growth factor response to acute systemic exercise in human skeletal muscle. J Appl Physiol 96:19–24

    Article  PubMed  CAS  Google Scholar 

  31. Jensen L, Pilegaard H, Neufer PD et al (2004) Effect of acute exercise and exercise training on VEGF splice variants in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 287:R397–R402

    Article  PubMed  CAS  Google Scholar 

  32. Jensen L, Bangsbo J, Hellsten Y (2004) Effect of high intensity training on capillarization and presence of angiogenic factors in human skeletal muscle. J Physiol 557:571–582

    Article  PubMed  CAS  Google Scholar 

  33. Gustafsson T, Ameln H, Fischer H et al (2005) VEGF-A splice variants and related receptor expression in human skeletal muscle following submaximal exercise. J Appl Physiol 98:2137–2146

    Article  PubMed  CAS  Google Scholar 

  34. Gustafsson T, Rundqvist H, Norrbom J et al (2007) The influence of physical training on the angiopoietin and VEGF-A systems in human skeletal muscle. J Appl Physiol 103:1012–1020

    Article  PubMed  CAS  Google Scholar 

  35. Egginton S, Zhou AL, Brown MD et al (2001) Unorthodox angiogenesis in skeletal muscle. Cardiovasc Res 49:634–646

    Article  PubMed  CAS  Google Scholar 

  36. Gustafsson T (2011) Vascular remodelling in human skeletal muscle. Biochem Soc Trans 39:1628–1632

    Article  PubMed  CAS  Google Scholar 

  37. Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307

    Article  PubMed  CAS  Google Scholar 

  38. Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447

    Article  PubMed  CAS  Google Scholar 

  39. Folkman J (1985) Toward an understanding of angiogenesis: search and discovery. Perspect Biol Med 29:10–36

    PubMed  CAS  Google Scholar 

  40. Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9:685–693

    Article  PubMed  CAS  Google Scholar 

  41. Prior BM, Yang HT, Terjung RL (2004) What makes vessels grow with exercise training? J Appl Physiol 97:1119–1128

    Article  PubMed  Google Scholar 

  42. Qutub AA, Mac Gabhann F, Karagiannis ED et al (2009) Multiscale models of angiogenesis. IEEE Eng Med Biol Mag 28:14–31

    Article  PubMed  Google Scholar 

  43. Yancopoulos GD, Davis S, Gale NW et al (2000) Vascular-specific growth factors and blood vessel formation. Nature 14:242–248

    Article  Google Scholar 

  44. Egginton S (2011) Physiological factors influencing capillary growth. Acta Physiol (Oxf) 202:225–239

    Article  CAS  Google Scholar 

  45. Djonov V, Baum O, Burri PH (2003) Vascular remodeling by intussusceptive angiogenesis. Cell Tissue Res 314:107–117

    Article  PubMed  Google Scholar 

  46. Gianni-Barrera R, Trani M, Reginato S et al (2011) To sprout or to split? VEGF, Notch and vascular morphogenesis. Biochem Soc Trans 39:1644–1648

    Article  PubMed  CAS  Google Scholar 

  47. Styp-Rekowska B, Hlushchuk R, Pries AR et al (2011) Intussusceptive angiogenesis: pillars against the blood flow. Acta Physiol (Oxf) 202:213–223

    Article  CAS  Google Scholar 

  48. Makanya AN, Hlushchuk R, Djonov VG (2009) Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling. Angiogenesis 12:113–123

    Article  PubMed  CAS  Google Scholar 

  49. Burri PH, Djonov V (2002) Intussusceptive angiogenesis—the alternative to capillary sprouting. Mol Aspects Med 23:S1–S27

    Article  PubMed  Google Scholar 

  50. Hobson B, Denekamp J (1984) Endothelial proliferation in tumours and normal tissues: continuous labelling studies. Br J Cancer 49:405–413

    Article  PubMed  CAS  Google Scholar 

  51. Haas TL, Milkiewicz M, Davis SJ et al (2000) Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle. Am J Physiol Heart Circ Physiol 279:H1540–H1547

    PubMed  CAS  Google Scholar 

  52. Hansen-Smith FM, Hudlicka O, Egginton S (1996) In vivo angiogenesis in adult rat skeletal muscle: early changes in capillary network architecture and ultrastructure. Cell Tissue Res 286:123–136

    Article  PubMed  CAS  Google Scholar 

  53. Paku S, Paweletz N (1991) First steps of tumor-related angiogenesis. Lab Invest 65:334–346

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  55. Gerhardt H, Golding M, Fruttiger M et al (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161:1163–1177

    Article  PubMed  CAS  Google Scholar 

  56. Benjamin LE, Golijanin D, Itin A et al (1999) Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 103:159–165

    Article  PubMed  CAS  Google Scholar 

  57. Dor Y, Djonov V, Abramovitch R et al (2002) Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy. EMBO J 21:1939–1947

    Article  PubMed  CAS  Google Scholar 

  58. Caduff JH, Fischer LC, Burri PH (1986) Scanning electron microscope study of the developing microvasculature in the postnatal rat lung. Anat Rec 216:154–164

    Article  PubMed  CAS  Google Scholar 

  59. Patan S, Haenni B, Burri PH (1996) Implementation of intussusceptive microvascular growth in the chicken chorioallantoic membrane (CAM): 1. pillar formation by folding of the capillary wall. Microvasc Res 51:80–98

    Article  PubMed  CAS  Google Scholar 

  60. Kauffman SL, Burri PH, Weibel ER (1974) The postnatal growth of the rat lung. II. Autoradiography. Anat Rec 180:63–76

    Article  PubMed  CAS  Google Scholar 

  61. Lloyd PG, Prior BM, Li H et al (2005) VEGF receptor antagonism blocks arteriogenesis, but only partially inhibits angiogenesis, in skeletal muscle of exercise-trained rats. Am J Physiol Heart Circ Physiol 288:H759–H768

    Article  PubMed  CAS  Google Scholar 

  62. Williams JL, Cartland D, Rudge JS et al (2006) VEGF trap abolishes shear stress- and overload-­dependent angiogenesis in skeletal muscle. Microcirculation 13:499–509

    Article  PubMed  CAS  Google Scholar 

  63. Olfert IM, Howlett RA, Wagner PD et al (2010) Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis. Am J Physiol Regul Integr Comp Physiol 299:R1059–R1067

    Article  PubMed  CAS  Google Scholar 

  64. Forsythe JA, Jiang BH, Iyer NV et al (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16:4604–4613

    PubMed  CAS  Google Scholar 

  65. Shweiki D, Itin A, Soffer D et al (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 29:843–845

    Article  Google Scholar 

  66. Richardson RS, Duteil S, Wary C et al (2006) Human skeletal muscle intracellular oxygenation: the impact of ambient oxygen availability. J Physiol 571:415–424

    Article  PubMed  CAS  Google Scholar 

  67. Richardson RS, Noyszewski EA, Kendrick KF et al (1995) Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport. J Clin Invest 96:1916–1926

    Article  PubMed  CAS  Google Scholar 

  68. Mason SD, Howlett RA, Kim MJ et al (2004) Loss of skeletal muscle HIF-1alpha results in altered exercise endurance. PLoS Biol 2:e288

    Article  PubMed  CAS  Google Scholar 

  69. Ameln H, Gustafsson T, Sundberg CJ et al (2005) Physiological activation of hypoxia inducible factor-1 in human skeletal muscle. FASEB J 19:1009–1011

    PubMed  CAS  Google Scholar 

  70. Fraisl P, Mazzone M, Schmidt T et al (2009) Regulation of angiogenesis by oxygen and metabolism. Dev Cell 16:167–179

    Article  PubMed  CAS  Google Scholar 

  71. Hardie DG (2003) Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology 144:5179–5183

    Article  PubMed  CAS  Google Scholar 

  72. Ouchi N, Shibata R, Walsh K (2005) AMP-activated protein kinase signaling stimulates VEGF expression and angiogenesis in skeletal muscle. Circ Res 29:838–846

    Article  CAS  Google Scholar 

  73. Jensen L, Schjerling P, Hellsten Y (2004) Regulation of VEGF and bFGF mRNA expression and other proliferative compounds in skeletal muscle cells. Angiogenesis 7:255–267

    Article  PubMed  CAS  Google Scholar 

  74. Arany Z, Foo SY, Ma Y et al (2008) HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 451:1008–1012

    Article  PubMed  CAS  Google Scholar 

  75. Richardson RS, Wagner H, Mudaliar SR, Saucedo E, Henry R, Wagner PD (2000) Exercise adaptation attenuates VEGF gene expression in human skeletal muscle. Am J Physiol Heart Circ Physiol 279:H772–H778

    PubMed  CAS  Google Scholar 

  76. Neufeld G, Cohen T, Gengrinovitch S et al (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22

    PubMed  CAS  Google Scholar 

  77. Hoier B, Nordsborg N, Andersen S et al (2012) Pro- and anti-angiogenic factors in human skeletal muscle in response to acute exercise and training. J Physiol 590:595–606

    PubMed  CAS  Google Scholar 

  78. Rullman E, Rundqvist H, Wagsater D et al (2007) A single bout of exercise activates matrix metalloproteinase in human skeletal muscle. J Appl Physiol 102:2346–2351

    Article  PubMed  CAS  Google Scholar 

  79. Wahl P, Zinner C, Achtzehn S et al (2011) Effects of acid–base balance and high or low intensity exercise on VEGF and bFGF. Eur J Appl Physiol 111:1405–1413

    Article  PubMed  CAS  Google Scholar 

  80. Gavin TP, Drew JL, Kubik CJ et al (2007) Acute resistance exercise increases skeletal muscle angiogenic growth factor expression. Acta Physiol (Oxf) 191:139–146

    Article  CAS  Google Scholar 

  81. Rojas Vega S, Knicker A, Hollmann W et al (2010) Effect of resistance exercise on serum levels of growth factors in humans. Horm Metab Res 42:982–986

    Article  PubMed  CAS  Google Scholar 

  82. Takano H, Morita T, Iida H et al (2005) Hemodynamic and hormonal responses to a short-­term low-intensity resistance exercise with the reduction of muscle blood flow. Eur J Appl Physiol 95:65–73

    Article  PubMed  CAS  Google Scholar 

  83. Timmons JA, Jansson E, Fischer H et al (2005) Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans. BMC Biol 3:19

    Article  PubMed  CAS  Google Scholar 

  84. Olsson AK, Dimberg A, Kreuger J et al (2006) VEGF receptor signalling—in control of vascular function. Nat Rev Mol Cell Biol 7:359–371

    Article  PubMed  CAS  Google Scholar 

  85. Chen X, Li Y (2009) Role of matrix metalloproteinases in skeletal muscle: migration, differentiation, regeneration and fibrosis. Cell Adh Migr 3:337–341

    Article  PubMed  Google Scholar 

  86. Baum O, Ganster M, Baumgartner I et al (2007) Basement membrane remodeling in skeletal muscles of patients with limb ischemia involves regulation of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases. J Vasc Res 44:202–213

    Article  PubMed  CAS  Google Scholar 

  87. Carmeli E, Moas M, Lennon S et al (2005) High intensity exercise increases expression of matrix metalloproteinases in fast skeletal muscle fibres. Exp Physiol 90:613–619

    Article  PubMed  CAS  Google Scholar 

  88. Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34

    Article  PubMed  CAS  Google Scholar 

  89. Rullman E, Norrbom J, Stromberg A et al (2009) Endurance exercise activates matrix metalloproteinases in human skeletal muscle. J Appl Physiol 106:804–812

    Article  PubMed  CAS  Google Scholar 

  90. Deus AP, Bassi D, Simoes RP et al (2012) MMP(−2) expression in skeletal muscle after strength training. Int J Sports Med 33:137–141

    Article  PubMed  CAS  Google Scholar 

  91. Heinemeier KM, Olesen JL, Haddad F et al (2007) Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types. J Physiol 582:1303–1316

    Article  PubMed  CAS  Google Scholar 

  92. Suhr F, Brixius K, de Marees M et al (2007) Effects of short-term vibration and hypoxia during high-intensity cycling exercise on circulating levels of angiogenic regulators in humans. J Appl Physiol 103:474–483

    Article  PubMed  CAS  Google Scholar 

  93. Urso ML, Pierce JR, Alemany JA et al (2009) Effects of exercise training on the matrix metalloprotease response to acute exercise. Eur J Appl Physiol 106:655–663

    Article  PubMed  CAS  Google Scholar 

  94. Haas TL, Davis SJ, Madri JA (1998) Three-dimensional type I collagen lattices induce coordinate expression of matrix metalloproteinases MT1-MMP and MMP-2 in microvascular endothelial cells. J Biol Chem 273:3604–3610

    Article  PubMed  CAS  Google Scholar 

  95. Yan C, Boyd DD (2007) Regulation of matrix metalloproteinase gene expression. J Cell Physiol 211:19–26

    Article  PubMed  CAS  Google Scholar 

  96. Mester J, Kleinoder H, Yue Z (2006) Vibration training: benefits and risks. J Biomech 39:1056–1065

    Article  PubMed  CAS  Google Scholar 

  97. Davis S, Aldrich TH, Jones PF et al (1996) Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 87:1161–1169

    Article  PubMed  CAS  Google Scholar 

  98. Maisonpierre PC, Suri C, Jones PF et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60

    Article  PubMed  CAS  Google Scholar 

  99. Holash J, Maisonpierre PC, Compton D et al (1999) Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284:1994–1998

    Article  PubMed  CAS  Google Scholar 

  100. Asahara T, Chen D, Takahashi T et al (1998) Tie2 receptor ligands, angiopoietin-1 and angiopoietin-­2, modulate VEGF-induced postnatal neovascularization. Circ Res 83:233–240

    Article  PubMed  CAS  Google Scholar 

  101. Bonsignore MR, Morici G, Riccioni R et al (2010) Hemopoietic and angiogenetic progenitors in healthy athletes: different responses to endurance and maximal exercise. J Appl Physiol 109:60–67

    Article  PubMed  CAS  Google Scholar 

  102. Dickson MC, Martin JS, Cousins FM et al (1995) Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 121:1845–1854

    PubMed  CAS  Google Scholar 

  103. Heinemeier KM, Bjerrum SS, Schjerling P et al (2011) Expression of extracellular matrix components and related growth factors in human tendon and muscle after acute exercise. Scand J Med Sci Sports 23:1–12

    Google Scholar 

  104. Czarkowska-Paczek B, Bartlomiejczyk I, Przybylski J (2006) The serum levels of growth factors: PDGF, TGF-beta and VEGF are increased after strenuous physical exercise. J Physiol Pharmacol 57:189–197

    PubMed  CAS  Google Scholar 

  105. Stavri GT, Zachary IC, Baskerville PA et al (1995) Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells. Synergistic interaction with hypoxia. Circulation 92:11–14

    Article  PubMed  CAS  Google Scholar 

  106. Babaei S, Teichert-Kuliszewska K, Monge JC et al (1998) Role of nitric oxide in the angiogenic response in vitro to basic fibroblast growth factor. Circ Res 82:1007–1015

    Article  PubMed  CAS  Google Scholar 

  107. Gu JW, Gadonski G, Wang J et al (2004) Exercise increases endostatin in circulation of healthy volunteers. BMC Physiol 4:2

    Article  PubMed  Google Scholar 

  108. Hajitou A, Grignet C, Devy L et al (2002) The antitumoral effect of endostatin and angiostatin is associated with a down-regulation of vascular endothelial growth factor expression in tumor cells. FASEB J 16:1802–1804

    PubMed  CAS  Google Scholar 

  109. Kim YM, Hwang S, Kim YM et al (2002) Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1. J Biol Chem 277:27872–27879

    Article  PubMed  CAS  Google Scholar 

  110. Lee SJ, Jang JW, Kim YM et al (2002) Endostatin binds to the catalytic domain of matrix metalloproteinase-2. FEBS Lett 519:147–152

    Article  PubMed  CAS  Google Scholar 

  111. Li C, Harris MB, Venema VJ et al (2005) Endostatin induces acute endothelial nitric oxide and prostacyclin release. Biochem Biophys Res Commun 329:873–878

    Article  PubMed  CAS  Google Scholar 

  112. Wenzel D, Schmidt A, Reimann K et al (2006) Endostatin, the proteolytic fragment of collagen XVIII, induces vasorelaxation. Circ Res 98:1203–1211

    Article  PubMed  CAS  Google Scholar 

  113. Brixius K, Schoenberger S, Ladage D et al (2008) Long-term endurance exercise decreases antiangiogenic endostatin signalling in overweight men aged 50–60 years. Br J Sports Med 42:126–129

    Article  PubMed  CAS  Google Scholar 

  114. Bornstein P (1992) Thrombospondins: structure and regulation of expression. FASEB J 6:3290–3299

    PubMed  CAS  Google Scholar 

  115. Iruela-Arispe ML, Luque A, Lee N (2004) Thrombospondin modules and angiogenesis. Int J Biochem Cell Biol 36:1070–1078

    Article  PubMed  CAS  Google Scholar 

  116. Bonnefoy A, Moura R, Hoylaerts MF (2008) The evolving role of thrombospondin-1 in hemostasis and vascular biology. Cell Mol Life Sci 65(5):713–727

    Article  PubMed  CAS  Google Scholar 

  117. Kazerounian S, Yee KO, Lawler J (2008) Thrombospondins in cancer. Cell Mol Life Sci 65:700–712

    Article  PubMed  CAS  Google Scholar 

  118. Olfert IM, Breen EC, Gavin TP, Wagner PD (2006) Temporal thrombospondin-1 mRNA response in skeletal muscle exposed to acute and chronic exercise. Growth Factors 24:253–259

    Article  PubMed  CAS  Google Scholar 

  119. Murphy G, Houbrechts A, Cockett MI et al (1991) The N-terminal domain of tissue inhibitor of metalloproteinases retains metalloproteinase inhibitory activity. Biochemistry 30:8097–8102

    Article  PubMed  CAS  Google Scholar 

  120. Stetler-Stevenson WG, Seo DW (2005) TIMP-2: an endogenous inhibitor of angiogenesis. Trends Mol Med 11:97–103

    Article  PubMed  CAS  Google Scholar 

  121. Frederiksen CB, Lomholt AF, Lottenburger T et al (2008) Assessment of the biological variation of plasma tissue inhibitor of metalloproteinases-1. Int J Biol Markers 23:42–47

    PubMed  CAS  Google Scholar 

  122. Koskinen SO, Heinemeier KM, Olesen JL et al (2004) Physical exercise can influence local levels of matrix metalloproteinases and their inhibitors in tendon-related connective tissue. J Appl Physiol 96:861–864

    Article  PubMed  CAS  Google Scholar 

  123. Koskinen SO, Wang W, Ahtikoski AM et al (2001) Acute exercise induced changes in rat skeletal muscle mRNAs and proteins regulating type IV collagen content. Am J Physiol Regul Integr Comp Physiol 280:R1292–R1300

    PubMed  CAS  Google Scholar 

  124. O’Reilly MS, Holmgren L, Shing Y et al (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315–328

    Article  PubMed  Google Scholar 

  125. Sonoda H, Ohta H, Watanabe K et al (2006) Multiple processing forms and their biological activities of a novel angiogenesis inhibitor vasohibin. Biochem Biophys Res Commun 342:640–646

    Article  PubMed  CAS  Google Scholar 

  126. Kishlyansky M, Vojnovic J, Roudier E et al (2010) Striated muscle angio-adaptation requires changes in Vasohibin-1 expression pattern. Biochem Biophys Res Commun 399:359–364

    Article  PubMed  CAS  Google Scholar 

  127. Ribatti D (2007) The discovery of endothelial progenitor cells. An historical review. Leuk Res 31:439–444

    Article  PubMed  CAS  Google Scholar 

  128. Asahara T, Murohara T, Sullivan A et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

    Article  PubMed  CAS  Google Scholar 

  129. Ii M, Nishimura H, Iwakura A et al (2005) Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via “imported” nitric oxide synthase activity. Circulation 111:1114–1120

    Article  PubMed  Google Scholar 

  130. Rehman J, Li J, Parvathaneni L, Karlsson G et al (2004) Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells. J Am Coll Cardiol 43:2314–2318

    Article  PubMed  Google Scholar 

  131. Van Craenenbroeck EM, Vrints CJ, Haine SE et al (2008) A maximal exercise bout increases the number of circulating CD34+/KDR+endothelial progenitor cells in healthy subjects. Relation with lipid profile. J Appl Physiol 104:1006–1013

    Article  PubMed  CAS  Google Scholar 

  132. Laufs U, Werner N, Link A et al (2004) Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation 109:220–226

    Article  PubMed  CAS  Google Scholar 

  133. Laufs U, Urhausen A, Werner N et al (2005) Running exercise of different duration and intensity: effect on endothelial progenitor cells in healthy subjects. Eur J Cardiovasc Prev Rehabil 12:407–414

    Article  PubMed  Google Scholar 

  134. Steiner S, Niessner A, Ziegler S et al (2005) Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease. Atherosclerosis 181:305–310

    Article  PubMed  CAS  Google Scholar 

  135. Schlager O, Giurgea A, Schuhfried O et al (2011) Exercise training increases endothelial progenitor cells and decreases asymmetric dimethylarginine in peripheral arterial disease: a randomized controlled trial. Atherosclerosis 217:240–248

    Article  PubMed  CAS  Google Scholar 

  136. Sarto P, Balducci E, Balconi G et al (2007) Effects of exercise training on endothelial progenitor cells in patients with chronic heart failure. J Card Fail 13:701–708

    Article  PubMed  CAS  Google Scholar 

  137. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  138. Lee Y, Ahn C, Han J et al (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419

    Article  PubMed  CAS  Google Scholar 

  139. Lund E, Guttinger S, Calado A et al (2004) Nuclear export of microRNA precursors. Science 303:95–98

    Article  PubMed  CAS  Google Scholar 

  140. Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436:214–220

    Article  PubMed  CAS  Google Scholar 

  141. Chen JF, Mandel EM, Thomson JM et al (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38:228–233

    Article  PubMed  CAS  Google Scholar 

  142. Keller P, Vollaard NB, Gustafsson T et al (2011) A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype. J Appl Physiol 110:46–59

    Article  PubMed  CAS  Google Scholar 

  143. Dews M, Homayouni A, Yu D et al (2006) Augmentation of tumor angiogenesis by a Myc-­activated microRNA cluster. Nat Genet 38:1060–1065

    Article  PubMed  CAS  Google Scholar 

  144. Fasanaro P, D’Alessandra Y, Di Stefano V et al (2008) MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 283:15878–15883

    Article  PubMed  CAS  Google Scholar 

  145. Poliseno L, Tuccoli A, Mariani L et al (2006) MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108:3068–3071

    Article  PubMed  CAS  Google Scholar 

  146. Wang CH, Lee DY, Deng Z et al (2008) MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression. PLoS One 3:e2420

    Article  PubMed  CAS  Google Scholar 

  147. Pin AL, Houle F, Guillonneau M et al (2012) miR-20a represses endothelial cell migration by targeting MKK3 and inhibiting p38 MAP kinase activation in response to VEGF. Angiogenesis 14:1–14

    Google Scholar 

  148. Hu S, Huang M, Li Z et al (2010) MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. Circulation 122:S124–S131

    Article  PubMed  CAS  Google Scholar 

  149. Baggish AL, Hale A, Weiner RB et al (2011) Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training. J Physiol 589:3983–3994

    Article  PubMed  CAS  Google Scholar 

  150. Warburton DE, Katzmarzyk PT, Rhodes RE et al (2007) Evidence-informed physical activity guidelines for Canadian adults. Can J Public Health 98:S16–S68

    PubMed  Google Scholar 

  151. Elsman P, van’t Hof AW, de Boer MJ et al (2004) Role of collateral circulation in the acute phase of ST-segment-elevation myocardial infarction treated with primary coronary intervention. Eur Heart J 25:854–858

    Article  PubMed  CAS  Google Scholar 

  152. Habib GB, Heibig J, Forman SA et al (1991) Influence of coronary collateral vessels on myocardial infarct size in humans. Results of phase I thrombolysis in myocardial infarction (TIMI) trial. The TIMI Investigators. Circulation 83:739–746

    Article  PubMed  CAS  Google Scholar 

  153. Sabia PJ, Powers ER, Ragosta M et al (1992) An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. N Engl J Med 327:1825–1831

    Article  PubMed  CAS  Google Scholar 

  154. Beck EB, Erbs S, Mobius-Winkler S et al (2012) Exercise training restores the endothelial response to vascular growth factors in patients with stable coronary artery disease. Eur J Prev Cardiol 19:412–418

    Article  PubMed  Google Scholar 

  155. Onkelinx S, Cornelissen V, Defoor J et al (2011) The CAREGENE study: genetic variants of the endothelium and aerobic power in patients with coronary artery disease. Acta Cardiol 66:407–414

    PubMed  Google Scholar 

  156. Gustafsson T, Bodin K, Sylven C et al (2001) Increased expression of VEGF following exercise training in patients with heart failure. Eur J Clin Invest 31:362–366

    Article  PubMed  CAS  Google Scholar 

  157. Testa M, Ennezat PV, Vikstrom KL et al (2000) Modulation of vascular endothelial gene expression by physical training in patients with chronic heart failure. Ital Heart J 1:426–430

    PubMed  CAS  Google Scholar 

  158. Gatta L, Armani A, Iellamo F et al (2012) Effects of a short-term exercise training on serum factors involved in ventricular remodelling in chronic heart failure patients. Int J Cardiol 155:409–413

    Article  PubMed  Google Scholar 

  159. Hansen AH, Nielsen JJ, Saltin B et al (2010) Exercise training normalizes skeletal muscle vascular endothelial growth factor levels in patients with essential hypertension. J Hypertens 28:1176–1185

    Article  PubMed  CAS  Google Scholar 

  160. Duscha BD, Robbins JL, Jones WS et al (2011) Angiogenesis in skeletal muscle precede improvements in peak oxygen uptake in peripheral artery disease patients. Arterioscler Thromb Vasc Biol 31:2742–2748

    Article  PubMed  CAS  Google Scholar 

  161. Lee BC, Hsu HC, Tseng WY et al (2009) Effect of cardiac rehabilitation on angiogenic cytokines in postinfarction patients. Heart 95:1012–1018

    Article  PubMed  CAS  Google Scholar 

  162. Sandri M, Adams V, Gielen S et al (2005) Effects of exercise and ischemia on mobilization and functional activation of blood-derived progenitor cells in patients with ischemic syndromes: results of 3 randomized studies. Circulation 111:3391–3399

    Article  PubMed  Google Scholar 

  163. Zbinden R, Zbinden S, Meier P et al (2007) Coronary collateral flow in response to endurance exercise training. Eur J Cardiovasc Prev Rehabil 14:250–257

    Article  PubMed  Google Scholar 

  164. Troidl K, Schaper W (2012) Arteriogenesis versus angiogenesis in peripheral artery disease. Diabetes Metab Res Rev 28:27–29

    Article  PubMed  Google Scholar 

  165. Ferrari R, Bachetti T, Agnoletti L et al (1998) Endothelial function and dysfunction in heart failure. Eur Heart J 19:G41–G47

    PubMed  CAS  Google Scholar 

  166. Drexler H, Riede U, Munzel T et al (1992) Alterations of skeletal muscle in chronic heart failure. Circulation 85:1751–1759

    Article  PubMed  CAS  Google Scholar 

  167. Piepoli M, Ponikowski P, Clark AL et al (1999) A neural link to explain the “muscle hypothesis” of exercise intolerance in chronic heart failure. Am Heart J 137:1050–1056

    Article  PubMed  CAS  Google Scholar 

  168. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    Article  PubMed  CAS  Google Scholar 

  169. Verma VK, Singh V, Singh MP et al (2009) Effect of physical exercise on tumor growth regulating factors of tumor microenvironment: implications in exercise-dependent tumor growth retardation. Immunopharmacol Immunotoxicol 31:274–282

    Article  PubMed  CAS  Google Scholar 

  170. Jones LW, Viglianti BL, Tashjian JA et al (2010) Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer. J Appl Physiol 108:343–348

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

TAD is supported by research funding from Manitoba Health and Research Council (MHRC) and the Canadian Institutes for Health Research (CIHR). DSK is supported by a MHRC Graduate Studentship. The infrastructural support during this study was provided by the St. Boniface Hospital Research Foundation.

Author information

Authors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, MB, Canada, R2H 2A6

    Dustin Scott Kehler & Todd A. Duhamel Ph.D.

  2. Health, Leisure and Human Performance Research Institute, University of Manitoba, Winnipeg, MB, Canada

    Dustin Scott Kehler & Todd A. Duhamel Ph.D.

  3. University of Manitoba, Winnipeg, MB, Canada

    Dustin Scott Kehler, Naranjan S. Dhalla & Todd A. Duhamel Ph.D.

  4. Institute of Cardiovascular Sciences St. Boniface Hospital Research, University of Manitoba, 351 Tache Avenue, Winnipeg, Manitoba, Canada, R2H 2A6

    Naranjan S. Dhalla

Authors
  1. Dustin Scott Kehler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naranjan S. Dhalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Todd A. Duhamel Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Todd A. Duhamel Ph.D. .

Editor information

Editors and Affiliations

  1. Div. of Cardiovascular Medicine, UAMS, Little Rock, AR, USA, 4301 W Markham, Little Rock, 72205, Arkansas, USA

    Jawahar L. Mehta

  2. Institute of Cardiovascular Sciences, St. Boniface Hosp. Research, Univ. of Ma, 351 Tache Avenue, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kehler, D.S., Dhalla, N.S., Duhamel, T.A. (2013). Biochemical Mechanisms of Exercise-Induced Angiogenesis. In: Mehta, J., Dhalla, N. (eds) Biochemical Basis and Therapeutic Implications of Angiogenesis. Advances in Biochemistry in Health and Disease, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5857-9_11

Download citation

Publish with us

Policies and ethics

Search

Navigation