Feto-placental nitric oxide, asymmetric dimethylarginine and vascular endothelial growth factor (VEGF) levels and VEGF gene polymorphisms in severe preeclampsia

Abstract

Objective: To measure plasma nitric oxide (NO), asymmetric dimethylarginine (ADMA) and vascular endothelial growth factor (VEGF) levels and VEGF gene polymorphisms in fetal circulation in severe preeclampsia. Methods: Cord vessels of singleton gestations complicated with severe preeclampsia 36 weeks or more (n = 31) and controls were sampled upon delivery for analyte measuring. Additionally, DNA was extracted from umbilical vein whole blood to determine the frequency of VEGF gene single nucleotide polymorphisms (SNPs): −2578 A/C, −1498 C/T, −1154 A/G, −634 C/G and +936 C/T. Coefficient correlations between analyte levels and placental and neonatal weight were calculated. Results: NO plasma levels in umbilical vessels (artery and vein) were significantly higher in preeclampsia cases as compared to controls (4.67 ± 3.0 vs. 0.82 ± 0.90; 4.46 ± 3.0 vs. 0.82 ± 0.99 mmol/L, respectively, p = 0.0001 both). ADMA levels displayed a similar increased trend in both fetal vessels, but this did not reach statistical significance (2.57 ± 1.03 vs. 2.34 ± 0.57; 2.74 ± 0.94 vs. 2.42 ± 0.59 mmol/L, respectively, p > 0.05). VEGF was significantly lower in artery but not in vein in preeclampsia cases (200.48 ± 225.62 vs. 338.61 ± 287.03 pg/mL, p = 0.04). A significant positive correlation was found between NO and ADMA levels (artery and vein) among preeclampsia cases. Overall, the frequency of the studied VEGF gene SNPs did not differ among pre-eclamptic cases and controls; nevertheless, a significant trend toward lower umbilical vein VEGF levels was observed in pre-eclampsia cases in the presence of -2578 CC and −1154 AG genotypes. Conclusion: Near term gestations complicated with severe preeclampsia presented higher NO levels in fetal circulation, which correlated to ADMA and lower artery VEGF values. More research is warranted to confirm that selected VEGF SNPs may be associated with lower umbilical vein VEGF.

Keywords::

• Asymmetric dimethylarginine
• nitric oxide
• preeclampsia
• umbilical vessels
• vascular endothelial growth factor

Acknowledgments

The authors thank Paola Orlandi, PhD, for her invaluable help with gene polymorphism analysis, participating women and authorities of the Sotomayor Hospital for making this initiative possible.

Declaration of Interest: The authors report no conflicts of interest. This research was partially supported by AECID (“Agencia Española de Cooperación Internacional para el Desarrollo”) through grant B/017543/08 from the “Ministerio Español de Asuntos Exteriores y Cooperación” to Faustino R. Pérez-López, by the PRIN (“Progetti di Ricerca di Interesse Nazionale”) grant 2004057090-007 by “Ministero Istruzione Università Ricerca” (MIUR) to Tommaso Simoncini and by grant provided by the SINDE (“Sistema de Investigación y Desarrollo”), Universidad Católica de Santiago de Guayaquil, Ecuador (SIU # 68 Resolución Administrativa 038-2009) to Peter Chedraui.