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子痫前期蜕膜微血管内皮细胞表达的基质金属蛋白酶-1水平低于正常细胞。

Preeclamptic decidual microvascular endothelial cells express lower levels of matrix metalloproteinase-1 than normals.

作者信息

Gallery E D, Campbell S, Arkell J, Nguyen M, Jackson C J

机构信息

Department of Renal Medicine, University of Sydney at Royal North Shore Hospital, St. Leonards, NSW, 2065, Australia.

出版信息

Microvasc Res. 1999 May;57(3):340-6. doi: 10.1006/mvre.1998.2142.

Abstract

In preeclampsia, invasion of intrauterine decidual blood vessels by placental cytotrophoblasts is significantly reduced. This study examined the secretion of matrix metalloproteinases (MMP) by cultured human decidual endothelial cells from normal (NDEC) and preeclamptic (PEDEC) pregnancies. MMPs secreted into the culture medium were measured using zymography, Western blotting, and ELISA. Results were confirmed by Northern analysis. Phorbol myristate acetate, known to induce protease activity in other endothelial cell populations, stimulated MMP1, MMP9, and TIMP1 secretion in both NDEC and PEDEC. Neither tumor necrosis factor-alpha nor transforming growth factor-beta, both thought to have significant roles in the control of placentation, affected MMP secretion. MMP9 and TIMP1 levels were similar between the two cell types; however, MMP1 secretion was markedly different between the cell types. NDEC expressed higher levels of MMP1 under both basal (160 +/- 32 ng/10(6) cells) and stimulated (275 +/- 50) conditions compared to PEDEC (32 +/- 24 and 70 +/- 53, respectively). The lower MMP1 expression of decidual endothelial cells from preeclamptic women may inhibit endovascular invasion by cytotrophoblasts. These findings may, at least partly, explain the relative failure of trophoblasts to invade maternal decidual blood vessels in preeclamptic pregnancy.

摘要

在子痫前期,胎盘细胞滋养层细胞对子宫蜕膜血管的侵入显著减少。本研究检测了来自正常妊娠(NDEC)和子痫前期妊娠(PEDEC)的培养人蜕膜内皮细胞分泌基质金属蛋白酶(MMP)的情况。使用酶谱法、蛋白质印迹法和酶联免疫吸附测定法测量培养基中分泌的MMP。结果通过Northern分析得到证实。已知能诱导其他内皮细胞群体中蛋白酶活性的佛波酯肉豆蔻酸酯刺激了NDEC和PEDEC中MMP1、MMP9和TIMP1的分泌。肿瘤坏死因子-α和转化生长因子-β这两种被认为在胎盘形成控制中起重要作用的因子均未影响MMP的分泌。两种细胞类型中MMP9和TIMP1水平相似;然而,两种细胞类型之间MMP1的分泌明显不同。与PEDEC(分别为32±24和70±53)相比,NDEC在基础(160±32 ng/10⁶细胞)和刺激(275±50)条件下均表达更高水平的MMP1。子痫前期妇女蜕膜内皮细胞中较低的MMP1表达可能会抑制细胞滋养层细胞的血管内侵入。这些发现可能至少部分解释了子痫前期妊娠中滋养层细胞侵入母体蜕膜血管相对失败的原因。

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