Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia
Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia
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DOI：
10.1161/hypertensionaha.107.092098
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发表时间：
2007-10-01
期刊：
影响因子：
8.3
通讯作者：
Pollitt, N. Stephen
中科院分区：
文献类型：
--
作者：
Li, Zhihe;Zhang, Ying;Pollitt, N. Stephen
已知血管生成因子的抑制剂被上调，并且它们的水平在先兆子痫发作之前在母体循环中增加。我们通过在妊娠和非妊娠 Sprague-Dawley 大鼠中腺病毒过度表达可溶性血管内皮生长因子 (VEGF) 受体 sFlt-1（也称为 sVEGFR-1）复制了先前表征的先兆子痫模型。动物接受 0、100、200 或 400 μg/kg 的 VEGF121 治疗，每天一次或两次（每组 n = 8 只；总共 64 只），并通过检查收缩压、尿白蛋白和肌酐、肾脏组织病理学和肾小球基因表达谱与正常对照动物（每组 n = 4 只）进行比较。 sFlt-1 表达诱导高血压伴蛋白尿和肾小球内皮增生以及基因表达的显着变化。 VEGF121 治疗缓解了这些症状，并逆转了 268 个 sFlt-1 诱导的基因表达变化中的 125 个。 VEGF121 对先兆子痫大鼠模型具有有益作用，且对胎儿没有明显伤害。有必要进一步研究 VEGF121 作为先兆子痫的潜在治疗剂。
Inhibitors of angiogenic factors are known to be upregulated, and their levels increase in the maternal circulation before the onset of preeclampsia. We reproduced a previously characterized model of preeclampsia by adenoviral overexpression of the soluble vascular endothelial growth factor (VEGF) receptor sFlt-1 (also referred to as sVEGFR-1) in pregnant and nonpregnant Sprague-Dawley rats. Animals were treated with VEGF121 at 0, 100, 200, or 400 mu g/kg once or twice daily (n = 8 per group; 64 total) and compared with normal control animals (n = 4 per group) by examination of systolic blood pressure, urinary albumin and creatinine, renal histopathology, and glomerular gene expression profiling. sFlt-1 expression induced hypertension with proteinuria and glomerular endotheliosis and significant changes in gene expression. VEGF121 treatment alleviated these symptoms and reversed 125 of 268 sFlt-1-induced changes in gene expression. VEGF121 had beneficial effects in this rat model of preeclampsia without apparent harm to the fetus. Further study of VEGF121 as a potential therapeutic agent for preeclampsia is warranted.