An Examination of the Effect of Aspirin and Salicylic Acid on Soluble Fms-like Tyrosine Kinase-1 Release from Human Placental Trophoblasts.
An Examination of the Effect of Aspirin and Salicylic Acid on Soluble Fms-like Tyrosine Kinase-1 Release from Human Placental Trophoblasts.
复制标题
作者：
小剂量阿司匹林(LDA)可有效预防子痫前期，但其作用机制尚不清楚。相互矛盾的证据表明，它可能抑制胎盘滋养层细胞释放可溶性FMS样酪氨酸激酶-1(SFlt1)，sFlt1是先兆子痫的关键介质。我们研究了阿司匹林及其主要代谢物水杨酸是否以及在何种浓度下调节滋养层细胞sFlt1的释放和/或表达。培养人滋养层细胞系BeWo和HTR-8/SVneo；BeWo细胞还用1%氧气和常氧处理，以模拟先兆子痫胎盘的缺氧。细胞用阿司匹林或水杨酸处理24小时，浓度与LDA相关或更高浓度。检测sFlt1蛋白浓度(EL ISA)和mRNA表达(RT-PCR)。在常氧条件下，LDA相关浓度的阿司匹林(10~50µm ol/L)或水杨酸(20~100µm o l/L)对BeWo细胞sFlt1蛋白的释放和基因表达均无明显影响。但在较高浓度(阿司匹林为1μ/L，水杨酸为2 0 0mmoL/L)时，则可观察到抑制作用。低氧可促进BeWo细胞sFlt1蛋白的释放和mRNA的表达，但在LDA浓度下，阿司匹林和水杨酸对这些反应均无显著影响。同样，在LDA浓度下，这两种药物都没有改变常氧HTR-8/SVneo细胞sFlt1蛋白的分泌或mRNA的表达。我们认为，直接调节滋养层细胞释放或sFlt1的表达不太可能是LDA治疗子痫前期临床疗效的机制。
Low-dose aspirin (LDA) is efficacious in preventing preeclampsia, but its mechanism of action is unclear. Conflicting evidence suggests that it may inhibit placental trophoblast release of soluble fms-like tyrosine kinase-1 (sFlt1), a key mediator of preeclampsia. We examined whether, and at what concentrations, aspirin and its principal metabolite, salicylic acid, modulate sFlt1 release and/or expression in trophoblasts. Human trophoblast lines BeWo and HTR-8/SVneo were cultured; BeWo cells were also treated with 1% oxygen vs. normoxia to mimic hypoxia in preeclamptic placentas. Cells were treated with aspirin or salicylic acid vs. vehicle for 24 h at concentrations relevant to LDA and at higher concentrations. Protein concentrations (ELISA) and mRNA expression (RT-PCR) of sFlt1 were determined. Under normoxia, LDA-relevant concentrations of aspirin (10–50 µmol/L) or salicylic acid (20–100 µmol/L) had no significant effect on sFlt1 protein release or mRNA expression in BeWo cells. However, inhibition was observed at higher concentrations (1 mmol/L for aspirin and ≥200 μmol/L for salicylic acid). Hypoxia enhanced sFlt1 protein release and mRNA expression in BeWo cells, but these responses were not significantly affected by either aspirin or salicylic acid at LDA concentrations. Similarly, neither drug altered sFlt1 protein secretion or mRNA expression in normoxic HTR-8/SVneo cells at LDA concentrations. We suggest that direct modulation of trophoblast release or expression of sFlt1 is unlikely to be a mechanism underlying the clinical efficacy of LDA in preeclampsia.
登录
查看更多内容
影响因子：
3.8
作者：
Li, C.;Raikwar, N. S.;Santillan, M. K.;Santillan, D. A.;Thomas, C. P.
通讯作者：
Thomas, C. P.
DOI：
10.1152/ajpregu.00794.2005
发表时间：
2006-10-01
影响因子：
2.8
作者：
Nevo, Ori;Soleymanlou, Nima;Caniggia, Isabella
通讯作者：
Caniggia, Isabella
DOI：
10.1073/pnas.90.24.11693
发表时间：
1993-12-15
影响因子：
11.1
作者：
MITCHELL, JA;AKARASEREENONT, P;VANE, JR
通讯作者：
VANE, JR
影响因子：
2.9
作者：
BOCHNER, F;WILLIAMS, DB;LLOYD, JV
通讯作者：
LLOYD, JV
影响因子：
7.2
作者：
Han CS;Mulla MJ;Brosens JJ;Chamley LW;Paidas MJ;Lockwood CJ;Abrahams VM
通讯作者：
Abrahams VM