Angiogenic growth factor messenger ribonucleic acids in uterine natural killer cells

J Clin Endocrinol Metab. 2001 Apr;86(4):1823-34. doi: 10.1210/jcem.86.4.7418.


Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common disorders of women, including menorrhagia and endometriosis. In pregnancy, failure of the endometrial spiral arterioles to undergo remodeling leads to preeclampsia. Here we report that in addition to vascular endothelial growth factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta growth factor (PlGF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, PlGF, and Tie 2 changed during the menstrual cycle. Intense hybridization for VEGF-C and PlGF mRNAs was found in uterine nature killer cells in secretory phase endometrium and for Ang2 mRNA in the same cells in the late secretory phase. Interleukin-2 (IL-2) and IL-15 up-regulated VEGF-C, but not PlGF or Ang2, mRNA levels in isolated NK cells. Conditioned medium from decidual NK cells did not induce human umbilical vein endothelial cell apoptosis. These results indicate that human endometrium expresses a wide range of angiogenic growth factors and that uterine nature killer cells may play an important role in the abnormal endometrial angiogenesis that underlies a range of disorders affecting women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / genetics*
  • Angiogenesis Inducing Agents / metabolism
  • Angiopoietin-2
  • Apoptosis / drug effects
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Cytochrome c Group / metabolism
  • Endothelial Growth Factors / genetics
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology
  • Female
  • Humans
  • Interleukin-15 / pharmacology
  • Interleukin-2 / pharmacology
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / metabolism*
  • Menstrual Cycle / physiology
  • Neoplasm Proteins / genetics
  • Placenta Growth Factor
  • Pregnancy Proteins / genetics
  • Proteins / genetics
  • Proto-Oncogene Proteins*
  • RNA, Messenger / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism
  • Receptors, TIE
  • Receptors, Vascular Endothelial Growth Factor
  • Umbilical Veins / cytology
  • Umbilical Veins / physiology
  • Uterus / cytology
  • Uterus / metabolism*
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor Receptor-3


  • Angiogenesis Inducing Agents
  • Angiopoietin-2
  • Culture Media, Conditioned
  • Cytochrome c Group
  • Endothelial Growth Factors
  • Interleukin-15
  • Interleukin-2
  • MEN1 protein, human
  • Neoplasm Proteins
  • PGF protein, human
  • Pregnancy Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor C
  • Placenta Growth Factor
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Receptors, TIE
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-3