Aspirin inhibits expression of sFLT1 from human cytotrophoblasts induced by hypoxia, via cyclo-oxygenase 1.
Aspirin inhibits expression of sFLT1 from human cytotrophoblasts induced by hypoxia, via cyclo-oxygenase 1.
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DOI：
10.1016/j.placenta.2015.01.004
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发表时间：
2015-04
期刊：
影响因子：
3.8
通讯作者：
Thomas, C. P.
中科院分区：
文献类型：
--
作者：
Li, C.;Raikwar, N. S.;Santillan, M. K.;Santillan, D. A.;Thomas, C. P.
子痫前期循环可溶性FLT1 （sFLT1）水平升高可能在子痫的发展中起作用。阿司匹林被推荐用于预防先兆子痫。我们假设阿司匹林可能抑制sFlt1的产生。收集有和无先兆子痫妇女的胎盘。从正常胎盘中培养原代细胞滋养细胞（CTBs），并用阿司匹林、sc-560 （COX1抑制剂）或塞来昔布（COX-2抑制剂）处理。研究sFLT1、FLT1、COX1、COX2的表达。我们还研究了阿司匹林对HEK293细胞和HTR-8/SVNeo细胞中sFlt1表达的影响。与对照组相比，sFLT1在子痫前期胎盘中的表达增加，暴露于2% O2的CTBs中sFLT1的表达和释放比对照组增加。3和12 mM浓度的阿司匹林降低了CTBs中sFLT1的表达和释放。阿司匹林还能抑制HTR-8/SVNeo和HEK293细胞中sFlt1的表达。Sc-560，而不是塞来昔布，降低了sFLT1的表达和CTBs的释放。阿司匹林和sc-560还能降低缺氧诱导的CTBs中FLT1 mRNA的表达，并抑制COX1 mRNA的表达。本研究证实，sFLT1在子痫前期胎盘和暴露于缺氧的CTBs中表达增加。阿司匹林抑制CTBs和HTR-8/SVNeo中sFLT1的产生。Sc-560重现了阿司匹林对CTBs中sFLT1表达和释放的影响，表明阿司匹林的作用可能是通过抑制COX1介导的。该研究增加了我们对调节sFlt1表达机制的理解，并为阿司匹林预防子痫前期的作用提供了一个合理的解释。
Elevated circulating soluble FLT1 (sFLT1) levels in preeclampsia may play a role in its development. Aspirin is recommended for prevention of preeclampsia. We hypothesized that aspirin may inhibit the production of sFlt1. Placentas from women with and without preeclampsia were collected. Primary cytotrophoblasts (CTBs) were cultured from normal placentas and treated with aspirin, sc-560, a COX1 inhibitor or celecoxib, a COX-2 inhibitor. The expression of sFLT1, FLT1, COX1, COX2 was studied. The effect of aspirin on sFlt1 expression was also studied in HEK293 cells and in HTR-8/SVNeo cells. The expression of sFLT1 was increased in preeclamptic placentas compared to control placentas and the expression and release of sFLT1 increased in CTBs exposed to 2% O2 compared to controls. Aspirin at 3 and 12 mM concentration reduced the expression and release of sFLT1 in CTBs. Aspirin also inhibited sFlt1 expression from HTR-8/SVNeo and HEK293 cells. Sc-560, but not celecoxib, reduced sFLT1 expression and release from CTBs. Aspirin and sc-560 also reduced hypoxia-induced FLT1 mRNA expression and inhibited COX1 mRNA in CTBs. This study confirms that sFLT1 expression is increased in preeclamptic placentas and in CTBs exposed to hypoxia. Aspirin inhibits the production sFLT1 in CTBs and in HTR-8/SVNeo. Sc-560 recapitulated the effects of aspirin on sFLT1 expression and release in CTBs suggesting that the aspirin effect may be mediated via inhibition of COX1. The study increases our understanding of the mechanisms regulating sFlt1 expression and provides a plausible explanation for the effect of aspirin to prevent preeclampsia.
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影响因子：
5.8
作者：
Koga, K;Osuga, Y;Taketani, Y
通讯作者：
Taketani, Y
DOI：
10.1152/ajpcell.2000.278.5.c982
发表时间：
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影响因子：
5.5
作者：
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7.2
作者：
Han CS;Mulla MJ;Brosens JJ;Chamley LW;Paidas MJ;Lockwood CJ;Abrahams VM
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影响因子：
3.2
作者：
Bridges, Jason P.;Gilbert, Jeffrey S.;Colson, Drew;Gilbert, Sara A.;Dukes, Matthew P.;Ryan, Michael J.;Granger, Joey P.
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