Lactate elicits vascular endothelial growth factor from macrophages: a possible alternative to hypoxia

Wound Repair Regen. 2000 Sep-Oct;8(5):353-60. doi: 10.1111/j.1524-475x.2000.00353.x.


Macrophages respond to various stimuli to produce angiogenic factors but few mechanistic details are known. We examined the effects of hypoxia, lactate and nicotinamide on the expression of vascular endothelial growth factor by cultured macrophages. These agents were chosen because they down-regulate polyadenosine diphosphoribose levels. Following exposure, conditioned media were analyzed for vascular endothelial growth factor protein. Nicotinamide adenine dinucleotide, polyadenosine diphosphoribose, and vascular endothelial growth factor mRNA were measured in the cellular fraction. Angiogenic capacity of the conditioned media was tested in rabbit corneas and Matrigel implants. All three agents, hypoxia, lactate and nicotinamide, elicited significantly increased levels of vascular endothelial growth factor mRNA and vascular endothelial growth factor in the conditioned media, and these levels were paralleled by their angiogenic activity. Polyadenosine diphosphoribose in the cellular fraction was correspondingly depressed. Anti-vascular endothelial growth factor antibody inhibited most of the angiogenic response whereas anti-basic fibroblast growth factor antibody had little effect. We propose that redox changes associated with the alteration of cellular nicotinamide adenine dinucleotide and polyadenosine diphosphoribose are involved in lactate-mediated VEGF expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Biocompatible Materials
  • Blotting, Northern
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Collagen
  • Cornea / cytology
  • Drug Combinations
  • Drug Evaluation, Preclinical
  • Endothelial Growth Factors / immunology
  • Endothelial Growth Factors / metabolism*
  • Hypoxia / metabolism*
  • Immunoassay
  • Lactic Acid / pharmacology*
  • Laminin
  • Lymphokines / immunology
  • Lymphokines / metabolism*
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology
  • Niacinamide / pharmacology*
  • Oxidation-Reduction
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Proteoglycans
  • Rabbits
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Wound Healing / drug effects


  • Antibodies
  • Biocompatible Materials
  • Drug Combinations
  • Endothelial Growth Factors
  • Laminin
  • Lymphokines
  • Proteoglycans
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • matrigel
  • Niacinamide
  • Poly Adenosine Diphosphate Ribose
  • Lactic Acid
  • Collagen