Uric acid attenuates trophoblast invasion and integration into endothelial cell monolayers
Uric acid attenuates trophoblast invasion and integration into endothelial cell monolayers
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DOI：
10.1152/ajpcell.00593.2008
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发表时间：
2009-08-01
影响因子：
5.5
通讯作者：
Hubel, Carl A.
中科院分区：
文献类型：
--
作者：
Bainbridge, Shannon A.;Roberts, James M.;Hubel, Carl A.
班布里奇SA，Roberts JM，von Versen-Hoynck F，Koch J，Edmunds L，Hubel CA.尿酸减弱滋养层细胞的侵袭和与内皮细胞单层的整合。美国生理学杂志细胞生理学297：C440-C450，2009年。首次发表于2009年6月17日; doi：10.1152/ajpcell.00593.2008。高尿酸血症早在妊娠10周时发生，随后发生先兆子痫。此时，侵袭性滋养层细胞正在积极重塑子宫螺旋小动脉，整合并最终取代血管内皮衬里。在非妊娠人群中，尿酸对血管内皮有几种致病作用。因此，我们试图使用体外Matrigel侵袭测定来检查尿酸（0-7 mg/dl）对滋养层细胞通过细胞外基质侵袭的影响。我们还评估了在滋养层-内皮细胞共培养模型中滋养层细胞与子宫微血管内皮细胞单层的整合。此外，我们强调了氧化还原信号和滋养层细胞诱导的内皮细胞凋亡的重要性。尿酸引起浓度依赖性衰减滋养层细胞的侵袭和整合到子宫微血管内皮细胞单层。滋养层整合减弱似乎是滋养层诱导的内皮细胞凋亡减少的结果，可能是通过尿酸的细胞内抗氧化作用。在相关性试验中，与健康妊娠对照组的合并血清相比，先兆子痫妇女的合并血清（5%vol/vol）减弱了滋养层细胞整合到内皮细胞单层中的能力，并且当内源性尿酸先前用尿酸酶去除时，这种反应得到部分挽救。总之，这些数据支持这一假设，即先兆子痫妇女循环尿酸升高有助于疾病的发病机制，部分通过正常滋养层浸润和螺旋动脉血管重塑的衰减。
Bainbridge SA, Roberts JM, von Versen-Hoynck F, Koch J, Edmunds L, Hubel CA. Uric acid attenuates trophoblast invasion and integration into endothelial cell monolayers. Am J Physiol Cell Physiol 297: C440-C450, 2009. First published June 17, 2009; doi: 10.1152/ajpcell.00593.2008.-Hyperuricemia develops as early as 10 wk of gestation in women who later develop preeclampsia. At this time the invasive trophoblast cells are actively remodeling the uterine spiral arterioles, integrating into and finally replacing the vascular endothelial lining. In the nonpregnant population uric acid has several pathogenic effects on vascular endothelium. We therefore sought to examine the effects of uric acid (0-7 mg/dl) on trophoblast cell invasion through an extracellular matrix using an in vitro Matrigel invasion assay. We also assessed trophoblast integration into a uterine microvascular endothelial cell monolayer in a trophoblast-endothelial cell coculture model. Additionally, we addressed the importance of redox signaling and trophoblast-induced endothelial cell apoptosis. Uric acid elicited a concentration-dependent attenuation of trophoblast invasion and integration into a uterine microvascular endothelial cell monolayer. The attenuated trophoblast integration appeared to be the result of reduced trophoblast-induced endothelial cell apoptosis, likely through the intracellular antioxidant actions of uric acid. In a test of relevance, pooled serum (5% vol/vol) from preeclamptic women attenuated the ability of trophoblast cells to integrate into the endothelial cell monolayers compared with pooled serum from healthy pregnant controls, and this response was partially rescued when endogenous uric acid was previously removed with uricase. Taken together these data support the hypothesis that elevations in circulating uric acid in preeclamptic women contribute to the pathogenesis of the disorder, in part, through attenuation of normal trophoblast invasion and spiral artery vascular remodeling.