title: Pregnancy Augments VEGF-Stimulated In Vitro Angiogenesis and Vasodilator (NO and H2S) Production in Human Uterine Artery Endothelial Cells.
abstract: Augmented uterine artery (UA) production of vasodilators, including nitric oxide (NO) and hydrogen sulfide (H2S), has been implicated in pregnancy-associated and agonist-stimulated rise in uterine blood flow that is rate-limiting to pregnancy health.
  
  
  
  Developing a human UA endothelial cell (hUAEC) culture model from main UAs of nonpregnant (NP) and pregnant (P) women for testing a hypothesis that pregnancy augments endothelial NO and H2S production and endothelial reactivity to vascular endothelial growth factor (VEGF).
  
  
  
  Main UAs from NP and P women were used for developing hUAEC culture models. Comparisons were made between NP- and P-hUAECs in in vitro angiogenesis, activation of cell signaling, expression of endothelial NO synthase (eNOS) and H2S-producing enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase, and NO/H2S production upon VEGF stimulation.
  
  
  
  NP- and P-hUAECs displayed a typical cobblestone-like shape in culture and acetylated low-density lipoprotein uptake, stained positively for endothelial and negatively for smooth muscle markers, maintained key signaling proteins during passage, and had statistically significant greater eNOS and CBS proteins in P- vs NP-hUAECs. Treatment with VEGF stimulated in vitro angiogenesis and eNOS protein and NO production only in P-hUEACs and more robust cell signaling in P- vs NP-hUAECs. VEGF stimulated CBS protein expression, accounting for VEGF-stimulated H2S production in hUAECs.
  
  
  
  Comparisons between NP- and P-hUAECs reveal that pregnancy augments VEGF-stimulated in vitro angiogenesis and NO/H2S production in hUAECs, showing that the newly established hUAEC model provides a critical in vitro tool for understanding human uterine hemodynamics.
authors.affiliation: Department of Obstetrics & Gynecology, University of California, Irvine, California 92697.
authors.forename: Hong-Hai
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics & Gynecology, University of California, Irvine, California 92697.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Obstetrics & Gynecology, University of California, Irvine, California 92697.
authors.forename: Lili
authors.initials: L
authors.lastname: Sheibani
authors.affiliation: Department of Obstetrics & Gynecology, University of California, Irvine, California 92697.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lechuga
authors.affiliation: Department of Obstetrics & Gynecology, University of California, Irvine, California 92697.
authors.forename: Dong-Bao
authors.initials: DB
authors.lastname: Chen
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D002478:Cells, Cultured / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D066298:In Vitro Techniques; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D011247:Pregnancy; D012680:Sensitivity and Specificity; D055988:Uterine Artery / Q000166:cytology / Q000378:metabolism*; D014599:Uterus / Q000098:blood supply; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014665:Vasodilator Agents / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D009569:Nitric Oxide; D006862:Hydrogen Sulfide