Oxidative stress contributes to soluble fms-like tyrosine kinase-1 induced vascular dysfunction in pregnant rats.
Oxidative stress contributes to soluble fms-like tyrosine kinase-1 induced vascular dysfunction in pregnant rats.
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DOI：
10.1038/ajh.2009.24
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发表时间：
2009-05
影响因子：
3.2
通讯作者：
Granger, Joey P.
中科院分区：
文献类型：
--
作者：
Bridges, Jason P.;Gilbert, Jeffrey S.;Colson, Drew;Gilbert, Sara A.;Dukes, Matthew P.;Ryan, Michael J.;Granger, Joey P.
最近的证据表明，增加的氧化应激和促血管生成因子和抗血管生成因子如血管内皮生长因子（VEGF）和可溶性VEGF受体（sFlt-1）之间的平衡改变都有助于先兆子痫中的内皮功能障碍。我们假设长期输注sFlt-1以模拟在先兆子痫患者中观察到的增加会降低血浆VEGF浓度，增加血压（BP）和血管超氧化物水平，并导致妊娠大鼠内皮功能障碍。在妊娠第13-18天输注重组sFlt-1（500 ng/h）。在妊娠第18天测定血压、胎儿和胎盘重量、氧化应激和血管舒张。与输注载体的母鼠相比，血浆sFlt-1浓度（299 ± 33对100 ± 16 pg/ml; P < 0.01）和BP（117 ± 6对98 ± 4 mm Hg; P < 0.01）增加，而血浆游离VEGF浓度（570 ± 77对780 ± 48 pg/ml; P < 0.01）降低。sFlt-1大鼠具有较小的胎仔（1.3 ± 0.03 vs. 1.5 ± 0.04 g，P < 0.01）和胎盘（0.41 ± 0.01 vs. 0.47 ± 0.02 g; P < 0.05）。与载体输注的大鼠相比，sFlt-1中胎盘（180 ± 66对24 ± 2.3 RLU/min/mg; P < 0.05）和血管（34 ± 8对12 ± 5 RLU/min/mg; P < 0.05）超氧化物产生增加。与载体相比，sFlt-1输注组中对乙酰胆碱（Ach）和硝普钠（SNP）的血管舒张均降低（P < 0.05），并且这种降低被超氧化物清除剂Tiron减弱（P < 0.05）。这些数据表明母体sFlt-1升高和VEGF浓度降低导致氧化应激增加，导致妊娠期间血管功能障碍。
Recent evidence indicates that both increased oxidative stress and an altered balance between pro- and anti-angiogenic factors such as vascular-endothelial growth factor (VEGF) and the soluble VEGF receptor (sFlt-1) contribute to endothelial dysfunction in preeclampsia. We hypothesized that chronic infusion of sFlt-1 to mimic the increase observed in preeclamptic patients would reduce plasma VEGF concentrations, increase blood pressure (BP) and vascular superoxide levels, and cause endothelial dysfunction in the pregnant rat. Recombinant sFlt-1 was infused (500 ng/h) during days 13–18 of pregnancy. BP, fetal and placental weight, oxidative stress and vessel vasorelaxation were determined on day 18 of pregnancy. Plasma sFlt-1 concentrations (299 ± 33 vs. 100 ± 16 pg/ml; P < 0.01) and BP (117 ± 6 vs. 98 ± 4 mm Hg; P < 0.01) were increased, while plasma-free VEGF concentrations (570 ± 77 vs. 780 ± 48 pg/ml; P < 0.01) were decreased when compared to vehicle infused dams. sFlt-1 rats had smaller fetuses (1.3 ± 0.03 vs. 1.5 ± 0.04 g, P < 0.01) and placentas (0.41 ± 0.01 vs. 0.47 ± 0.02 g; P < 0.05). Placental (180 ± 66 vs. 24 ± 2.3 RLU/min/mg; P < 0.05) and vascular (34 ± 8 vs. 12 ± 5 RLU/min/mg; P < 0.05) superoxide production was increased in the sFlt-1 compared to vehicle infused rats. Vasorelaxation to acetylcholine (Ach) and sodium nitroprusside (SNP) were both decreased (P < 0.05) in the sFlt-1 infusion group compared to the vehicle and this decrease was attenuated (P < 0.05) by the superoxide scavenger Tiron. These data indicate elevated maternal sFlt-1 and decreased VEGF concentrations results in increased oxidative stress that contributes to vascular dysfunction during pregnancy.
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DOI：
10.1016/0002-9378(89)90665-0
发表时间：
1989-11-01
影响因子：
9.8
作者：
ROBERTS, JM;TAYLOR, RN;MCLAUGHLIN, MK
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DOI：
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