Angiogenic growth factor messenger ribonucleic acids in uterine natural killer cells

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common disorders of women, including menorrhag ia and endometriosis. In pregnancy, failure of the endometrial spiral arter ioles to undergo remodeling leads to preeclampsia. Here we report that in a ddition to vascular endothelial growth factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta gr owth factor (P1GF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, P1GF, an d Tie 2 changed during the menstrual cycle. Intense hybridization for VEGF- C and P1GF mRNAs was found in uterine nature killer cells in secretory phas e endometrium and for Ang2 mRNA in the same cells in the late secretory pha se. Interleukin-2 (IL-2) and IL-15 up-regulated VEGF-C, but not P1GF or Ang 2, mRNA levels in isolated NK cells. Conditioned medium from decidual NK ce lls did not induce human umbilical vein endothelial cell apoptosis. These r esults 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 dis orders affecting women.