HIV感染的南非黑人子痫前期妇女中的可溶性fms样酪氨酸激酶-1

Soluble fms-like tyrosine kinase-1 in HIV infected pre-eclamptic South African Black women.

作者信息

Govender N, Moodley J, Gathiram P, Naicker T

机构信息

Optics and Imaging Centre, University of KwaZulu-Natal, South Africa.

Womens' Health and HIV Research Group, University of KwaZulu-Natal, South Africa.

出版信息

Placenta. 2014 Aug;35(8):618-24. doi: 10.1016/j.placenta.2014.04.013. Epub 2014 May 14.

DOI:10.1016/j.placenta.2014.04.013

PMID:24880209

Abstract

INTRODUCTION

Hypertensive disorders of pregnancy are the commonest direct cause of maternal deaths in South Africa, 83% being attributed to pre-eclampsia. Elevated placental sFlt-1 levels are linked with angiogenic disruption and subsequent pre-eclampsia development. The impact of HIV infection on pre-eclampsia is controversial. Its effect on angiogenic imbalance in both normotensive and pre-eclamptic pregnancies remains unknown.

METHODS

We examined the immunolocalisation of both membrane bound and soluble forms of Flt-1, within placentae of HIV negative and positive normotensive and pre-eclamptic pregnancies at term using immunohistochemistry and immuno-electron microscopy.

RESULTS

Strong Flt-1 and sFlt-1 immunoreactivity was observed within endothelial, syncytio and cytotrophoblast cells. Subcellularly, gold particles were localised predominantly within the endoplasmic reticulum and mitochondria and occurring free within the cytoplasm. There was no significant effect of HIV on Flt-1 and sFlt-1 immunoexpression in both exchange and stem villi. A significant effect of type of pregnancy (normotensive vs pre-eclamptic) on Flt-1 and sFlt-1 immunoexpression (p = 0.003) within exchange rather than stem villi, indicated that the pre-eclamptic had elevated Flt-1 and sFlt-1 expressions compared to the normotensive pregnant women. There was no interaction between HIV and pregnancy type (normotensive vs pre-eclampsia) for Flt-1 and sFlt-1 expressions in both exchange and stem villi. A weak correlation of Flt-1 and sFlt-1 intensity between the exchange and stem villi was noted.

DISCUSSION

Elevated immunoexpression of Flt-1 and sFlt-1 within trophoblasts suggests an autocrine mode of action on trophoblast invasion and differentiation thereby contributing to abnormal placentation with consequential endothelial dysfunction in pre-eclampsia.

CONCLUSION

Irrespective of the HIV status, placental Flt-1 and sFlt-1 expressions remain elevated in pre-eclampsia compared to normotensive pregnancies.

摘要

引言

妊娠高血压疾病是南非孕产妇死亡最常见的直接原因，其中83%归因于子痫前期。胎盘可溶性血管内皮生长因子受体-1（sFlt-1）水平升高与血管生成破坏及随后的子痫前期发展有关。HIV感染对子痫前期的影响存在争议。其对血压正常和子痫前期妊娠中血管生成失衡的影响尚不清楚。

方法

我们采用免疫组织化学和免疫电子显微镜技术，研究了足月时HIV阴性和阳性血压正常及子痫前期妊娠胎盘内膜结合型和可溶性Flt-1的免疫定位。

结果

在内皮细胞、合体滋养层细胞和细胞滋养层细胞内观察到强烈的Flt-1和sFlt-1免疫反应性。在亚细胞水平，金颗粒主要定位于内质网和线粒体内，并游离于细胞质中。HIV对交换绒毛和干绒毛中Flt-1和sFlt-1免疫表达无显著影响。妊娠类型（血压正常与子痫前期）对交换绒毛而非干绒毛中Flt-1和sFlt-1免疫表达有显著影响（p = 0.003），表明子痫前期孕妇的Flt-1和sFlt-1表达高于血压正常的孕妇。在交换绒毛和干绒毛中，HIV与妊娠类型（血压正常与子痫前期）之间对于Flt-1和sFlt-1表达没有相互作用。观察到交换绒毛和干绒毛中Flt-1和sFlt-1强度之间存在弱相关性。