Invasive trophoblasts stimulate vascular smooth muscle cell apoptosis by a Fas ligand-dependent mechanism
Invasive trophoblasts stimulate vascular smooth muscle cell apoptosis by a Fas ligand-dependent mechanism
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DOI：
10.2353/ajpath.2006.060265
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发表时间：
2006-11-01
影响因子：
6
通讯作者：
Whitley, Guy St J.
中科院分区：
文献类型：
--
作者：
Harris, Lynda K.;Keogh, Rosemary J.;Whitley, Guy St J.
在怀孕期间，滋养细胞从胎盘迁移到子宫螺旋动脉，将其转化为缺乏血管收缩特性的宽通道。在病理性妊娠中，这个过程是不完整的。为了确定螺旋动脉重构的基本事件，我们研究了滋养细胞对血管平滑肌细胞（SMCs）的影响。本研究首次证明了SMCs的凋亡可以通过入侵滋养细胞而启动。当滋养层;将分离自正常胎盘（原代滋养细胞）或条件培养基灌注到螺旋或脐动脉段，SMCs发生凋亡。用原代滋养层细胞、原代滋养层细胞条件培养基或滋养层细胞衍生细胞系（SGHPL-4）培养人主动脉SMC （HASMCs）也显著增加了SMC的凋亡。Fas在螺旋动脉SMCs中表达，Fas激活抗体触发HASMC凋亡。此外，Fas配体（FasL）阻断抗体显著抑制原代滋养层细胞、SGHPL-4或滋养层细胞条件培养基诱导的HASMC凋亡。消耗原代滋养细胞条件培养基中的FasL也能原位消除血管中SMC的凋亡。这些结果表明，入侵滋养细胞释放可溶性FasL引发的细胞凋亡导致妊娠期间螺旋动脉壁平滑肌的损失。
During pregnancy, trophoblasts migrate from the placenta into uterine spiral arteries, transforming them into wide channels that lack vasoconstrictive properties. In pathological pregnancies, this process is incomplete. To define the fundamental events involved in spiral artery remodeling, we have studied the effect of trophoblasts on vascular smooth muscle cells (SMCs). Here we demonstrate for the first time that apoptosis of SMCs can be initiated by invading trophoblasts. When trophoblasts; isolated from normal placenta (primary trophoblasts) or conditioned medium was perfused into spiral or umbilical artery segments, apoptosis of SMCs resulted. Culture of human aortic SMCs (HASMCs) with primary trophoblasts, primary trophoblast-conditioned medium, or a trophoblast-derived cell line (SGHPL-4) also significantly increased SMC apoptosis. Fas is expressed by spiral artery SMCs, and a Fas-activating antibody triggered HASMC apoptosis. Furthermore, a Fas ligand (FasL)-blocking antibody significantly inhibited HASMC apoptosis induced by primary trophoblasts, SGHPL-4, or trophoblast-conditioned medium. Depleting primary trophoblast-conditioned medium of FasL also abrogated SMC apoptosis in vessels in situ. These results suggest that apoptosis triggered by the release of soluble FasL from invading trophoblasts contributes to the loss of smooth muscle from the wafts of spiral arteries during pregnancy.