Lactate, with Oxygen, Incites Angiogenesis

  • Thomas K. Hunt
  • Rummana Aslam
  • Zamir Hussain
  • Stefan Beckert
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 614)


Lactate has been reconsidered! As we now know, most is produced aerobically We report that lactate accumulation commonly occurs in the presence of oxygen and is sufficient to instigate signals for angiogenesis and connective tissue deposition. These include vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF beta), interleukin-1 (IL-1), and hypoxia-inducible factor (hif-1alpha). This paper, a mini-review, is occasioned by new data showing increased presence of VEGF and angiogenesis in an oxygenated site by adding a slow-release source of lactate into Matrigel® and implanting the Matrigel subcutaneously in mice.


Vascular Endothelial Growth Factor Collagen Deposition Wound Repair Vascular Endothelial Growth Factor Promoter Vascular Endothelial Growth Factor Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Q. P. Ghani, S. Wagner, H. D. Becker, T. K. Hunt, M. Z. Hussain. Regulatory role of lactate in wound repair. Methods Enzymol. 2004; 381:565–75.PubMedCrossRefGoogle Scholar
  2. 2.
    J. S. Constant, J. J. Feng, D. D. Zabel, H. Yuan, D. Y. Suh, H. Scheuenstuhl, T. K. Hunt, M. Z. Hussain. Lactate elicits vascular endothelial growth factor from macrophages: a possible alternative to hypoxia. Wound Repair Regen. 2000 Sep–Oct; 8(5):353–60.Google Scholar
  3. 3.
    S. Beckert, F. Farrahi, R. S. Aslam, H. Scheuenstuhl, A. Konigsrainer, M. Z. Hussain, T. K. Hunt. Lactate stimulates endothelial cell migration. Wound Repair Regen. 2006 May–Jun; 14(3):321–4.Google Scholar
  4. 4.
    B. Formby, R. Stern. Lactate-sensitive response elements in genes involved in hyaluronan catabolism. Biochem Biophys Res Commun. 2003 May 23; 305(1):203–8.Google Scholar
  5. 5.
    L. B. Gladden. Lactate metabolism: a new paradigm for the third millennium. J Physiol. 2004 Jul 1; 558(Pt 1):5–30. Review.Google Scholar
  6. 6.
    J. E. Albina, B. Mastrofrancesco, J. A. Vessella, C. A. Louis, W. L. Henry, Jr., J. S. Reichner. HIF-1 expression in healing wounds: HIF-1alpha induction in primary inflammatory cells by TNF-alpha. Am J Cell Physiology. 2001 Dec; 281(6):C1971–7.Google Scholar
  7. 7.
    S. Biswas, M. Ray, S. Misra, D. P. Dutta, S. Ray. Is absence of pyruvate dehydrogenase complex in mitochondria a possible explanation of significant aerobic glycolysis by normal human leukocytes? FEBS Lett. 1998 Apr 3; 425(3):411–4.Google Scholar
  8. 8.
    O. Trabold, W. Wagner, C. Wicke, H. Scheuenstuhl, M. Z. Hussain, N. Rosen, A. Seremetiev, H. D. Becker, T. K. Hunt. Lactate and oxygen constitute a fundamental regulatory mechanism in wound healing. Wound Repair Regen. 2003 Nov–Dec;11(6):504–9.Google Scholar
  9. 9.
    Q. Liu, U. Berchner-Pfannschmidt, U. Moller, M. Brecht, C. Wotzlaw, H. Acker, K. Jungermann, T. A. Kietzmann. Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4302–7.Google Scholar
  10. 10.
    H. W. Hopf, J. J. Gibson, A. P. Angeles, J. S. Constant, J.J. Feng, M. D. Rollins, M. Z. Hussain, T. K. Hunt. Hyperoxia and angiogenesis. Wound Repair Regen. 2005 Nov–Dec;13(6):558–64.Google Scholar
  11. 11.
    A. Y. Sheikh, J. J. Gibson, M. D. Rollins, H. W. Hopf, Z. Hussain, T. K. Hunt. Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg. 2000 Nov; 135(11):1293–7Google Scholar
  12. 12.
    M.A. Ali, F. Yasui, S. Matsugo, T. Konishi. The lactate-dependent enhancement of hydroxyl radical generation by the Fenton reaction. Free Radic Res. 2000 May;32(5):429–38.Google Scholar
  13. 13.
    H. Lu, C. L. Dalgard, A. Mohyeldin, T. McFate, A. S. Tait, A. Verma. Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J Biol Chem. 2005 Dec 23;280(51):41928–39.Google Scholar
  14. 14.
    C. K. Sen, S. Khanna, B. M. Babior, T. K. Hunt, E. C. Ellison, S. Roy. Oxidant-induced vascular endothelial growth factor expression in human keratinocytes and cutaneous wound healing. J Biol Chem. 2002 Sep 6;277(36):33284–90.Google Scholar
  15. 15.
    D. D. Zabel, J. J. Feng, H. Scheuenstuhl, T. K. Hunt, M. Z. Hussain. Lactate stimulation of macrophage-derived angiogenic activity is associated with inhibition of Poly (ADP-ribose) synthesis. Lab Invest. 1996; 74:644–9.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Thomas K. Hunt
    • 1
  • Rummana Aslam
    • 1
  • Zamir Hussain
    • 1
  • Stefan Beckert
    • 1
  1. 1.Department of SurgeryUniversity of California Medical CenterSan Francisco

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