Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta.
Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta.
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DOI：
10.1016/j.ajog.2016.12.029
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发表时间：
2017-03
影响因子：
9.8
通讯作者：
Romero R
中科院分区：
文献类型：
--
作者：
Labarrere CA;DiCarlo HL;Bammerlin E;Hardin JW;Kim YM;Chaemsaithong P;Haas DM;Kassab GS;Romero R
在先兆子痫、胎儿生长受限、胎儿死亡和胎膜完整或破裂的自发性早产中，螺旋动脉的生理性转化失败已有报道。生理转化失败的螺旋动脉易发生动脉粥样硬化样病变。子痫前期与动脉粥样硬化性疾病之间、动脉粥样硬化病变与动脉粥样硬化之间有显著的相似性。内皮细胞活化，通过细胞间黏附分子-1的表达来确定，存在于心脏移植的动脉粥样硬化样病变中，被认为是排斥反应的表现。同样，内皮细胞激活/功能障碍也与动脉粥样硬化和子痫前期的病理生理学有关。细胞间黏附分子-1过表达激活的内皮细胞比未激活的内皮细胞对滋养层移位的抵抗力更强，这可能是生理转化失败的产科综合征中浅螺旋动脉滋养细胞侵袭的原因之一。探讨螺旋动脉生理性转化失败是否与胎盘基板绒毛外滋养细胞和/或螺旋动脉内皮细胞激活及急性动脉粥样硬化有关。对123例胎盘(孕19~42周)进行横断面研究，包括正常妊娠(n=22)、胎膜早破(n=26)、早产(n=23)、子痫前期(n=27)、胎儿宫内死亡(n=15)和小于胎龄儿(n=10)。通过免疫组织化学方法确定螺旋动脉生理性转化失败和细胞激活的存在，每个胎盘的胎盘基板的中位数为4条(最小：1条；最大：9条)。通过细胞间黏附分子-1(ICAM-1)的表达来确定内皮/滋养层细胞的激活。检查显微镜切片的调查人员对临床诊断视而不见。胎盘组之间的配对比较采用Fisher‘s Exact和Wilcoxon秩和检验，采用Bonferroni调整的显著性水平(0.025)。87%(94/108)的胎盘有螺旋动脉且基板生理性转化失败(肌动蛋白阳性和细胞角蛋白阴性)，0%(0/15)的胎盘仅有螺旋动脉生理性转化完全(细胞角蛋白阳性和肌动蛋白阴性)，动脉内皮细胞和/或间质绒毛外滋养层细胞对ICAM-1活化标志物呈阳性反应(P<；.001)。激活胎盘螺旋动脉内皮细胞的表达与胎盘间质绒毛外滋养细胞ICAM-1的表达呈显著正相关(R2=0.84)。ICAM-1阳性的胎盘中有31.9%(30/94)的胎盘螺旋动脉生理性转化完全和/或部分失败，ICAM-1阴性的14例生理性转化失败的胎盘中无一例发生动脉粥样硬化病变，15例螺旋动脉生理性转化完全失败的胎盘中无一例发生动脉粥样硬化病变(P=.001)。所有伴有动脉粥样硬化的胎盘(30/30,100%)均为伴有螺旋动脉内皮细胞和间质绒毛外滋养细胞活化的胎盘。胎盘基板螺旋动脉生理性转化失败与间质绒毛外滋养细胞和动脉内皮细胞活化以及螺旋动脉粥样硬化发生率增加有关。这些发现可用于改善胎盘床不同疾病的特征，例如改进现有的工具，用于早期预测早产、先兆子痫和其他异常妊娠的风险。
Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation and considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. To determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. A cross-sectional study of 123 placentas (19-42 weeks’ gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1 (ICAM-1). Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with the Fisher’s exact and Wilcoxon rank sum tests using a Bonferroni-adjusted level of significance (.025). 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation (actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation (cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the ICAM-1 activation marker (P < .001). A significant correlation (R2 = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast ICAM-1 (P < .001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries that were ICAM-1-positive, in none of the 14 placentas with failure of physiologic transformation that were ICAM-1-negative, and in none of the 15 placentas with complete spiral artery physiologic transformation without failure (P = .001). All placentas (30/30, 100%) with atherosis were identified in placentas having concomitant spiral artery endothelial and interstitial extravillous trophoblast activation. Failure of spiral artery physiologic transformation in the placental basal plate is associated with interstitial extravillous trophoblast and arterial endothelial activation along with increased frequency of spiral artery atherosis. These findings may be used to improve the characterization of different disorders of the placental bed such as in refining the existing tools for the early prediction of risk for preterm, preeclamptic, and other abnormal pregnancies.
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DOI：
10.1038/nrneph.2014.102
发表时间：
2014-08
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Chaiworapongsa T;Chaemsaithong P;Yeo L;Romero R
通讯作者：
Romero R
影响因子：
7.3
作者：
Ball, E;Bulmer, JN;Robson, SC
通讯作者：
Robson, SC
DOI：
10.3109/14767058.2011.589932
发表时间：
2011-10-01
影响因子：
1.8
作者：
Chaiworapongsa, Tinnakorn;Romero, Roberto;Hassan, Sonia S.
通讯作者：
Hassan, Sonia S.
影响因子：
9.8
作者：
Chaiworapongsa, T;Romero, R;Edwin, S
通讯作者：
Edwin, S
影响因子：
15.9
作者：
Boyd, EM
通讯作者：
Boyd, EM