Chedraui Peter, Solis Emilio J, Bocci Guido, Gopal Santhosh, Russo Eleonora, Escobar Gustavo S, Hidalgo Luis, Pérez-López Faustino R, Genazzani Andrea R, Mannella Paolo, Simoncini Tommaso
High Risk Pregnancy Labor and Delivery Unit, Enrique C. Sotomayor Obstetrics and Gynecology Hospital Guayaquil, Ecuador.
J Matern Fetal Neonatal Med. 2013 Feb;26(3):226-32. doi: 10.3109/14767058.2012.733760. Epub 2012 Oct 18.
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.
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.
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.
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.
检测重度子痫前期胎儿循环中血浆一氧化氮(NO)、不对称二甲基精氨酸(ADMA)和血管内皮生长因子(VEGF)水平以及VEGF基因多态性。
对36周及以上单胎妊娠合并重度子痫前期孕妇(n = 31)及对照组孕妇在分娩时采集脐带血管样本进行分析物检测。此外,从脐静脉全血中提取DNA,以确定VEGF基因单核苷酸多态性(SNP)的频率:-2578 A/C、-1498 C/T、-1154 A/G、-634 C/G和+936 C/T。计算分析物水平与胎盘和新生儿体重之间的系数相关性。
与对照组相比,子痫前期病例脐血管(动脉和静脉)中的血浆NO水平显著更高(分别为4.67±3.0 vs. 0.82±0.90;4.46±3.0 vs. 0.82±0.99 mmol/L,p均为0.0001)。ADMA水平在两条胎儿血管中均呈现类似的升高趋势,但未达到统计学意义(分别为2.57±1.03 vs. 2.34±0.57;2.74±0.94 vs. 2.42±0.59 mmol/L,p>0.05)。子痫前期病例动脉中的VEGF显著降低,但静脉中未降低(200.48±225.62 vs. 338.61±287.03 pg/mL,p = 0.04)。子痫前期病例中,动脉和静脉的NO与ADMA水平之间存在显著正相关。总体而言,子痫前期病例与对照组之间所研究的VEGF基因SNP频率无差异;然而,在存在-2578 CC和-1154 AG基因型的子痫前期病例中,观察到脐静脉VEGF水平有显著降低的趋势。
近足月妊娠合并重度子痫前期的胎儿循环中NO水平较高,这与ADMA以及动脉VEGF值降低相关。需要更多研究来证实所选的VEGF SNP可能与脐静脉VEGF降低有关。