Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome, Italy.
Biol Reprod. 2010 Aug 1;83(2):212-9. doi: 10.1095/biolreprod.110.083410. Epub 2010 Apr 14.
Antiphospholipid antibodies (aPL) represent an important risk factor for thrombosis and recurrent miscarriage in patients with antiphospholipid syndrome (APS). The mechanisms of aPL-mediated pregnancy failure have been researched. Previous studies demonstrated that aPL bind trophoblast cells, reducing proliferation, human chorionic gonadotrophin release, and in vitro invasiveness. Recent data suggest that aPL are also able to react with human decidual cells, inducing a proinflammatory phenotype. Decidua, a newly formed tissue on the maternal side of the human placenta, is characterized by active angiogenesis and structural modifications of the spiral arteries in early pregnancy. Since angiogenesis is a critical component of normal placentation, the purpose of our study was to evaluate the role of aPL on human endometrial angiogenesis. For this reason, we investigated the effect of aPL on in vitro endometrial endothelial cell (HEEC) angiogenesis, VEGF secretion by ELISA, matrix metalloproteinases (MMPs) activity by gelatin zymography, and DNA binding activity of NFKB by a sensitive multiwell colorimetric assay. Furthermore, we performed experiments to study whether aPL affects in vivo angiogenesis in a murine model. We found that aPL significantly decrease the number and the total length of the tubules formed by HEEC on in vitro Matrigel assay and reduce newly formed vessels in aPL-inoculated mice. Moreover, aPL reduce significantly both VEGF and MMPs production and, at the nuclear level, NFKB DNA binding activity. From our results, it appears that aPL are associated with an inhibition of angiogenesis, suggesting further additional mechanisms to explain the defective placentation in the APS.
抗磷脂抗体（aPL）是抗磷脂综合征（APS）患者血栓形成和复发性流产的重要危险因素。已经研究了 aPL 介导的妊娠失败的机制。先前的研究表明，aPL 结合滋养层细胞，减少增殖、人绒毛膜促性腺激素释放和体外侵袭性。最近的数据表明，aPL 还能够与人类蜕膜细胞反应，诱导促炎表型。蜕膜是胎盘母体侧新形成的组织，其特征是早期妊娠中血管生成活跃和螺旋动脉结构的改变。由于血管生成是正常胎盘形成的关键组成部分，我们研究的目的是评估 aPL 对人子宫内膜血管生成的作用。为此，我们研究了 aPL 对体外子宫内膜内皮细胞（HEEC）血管生成、ELISA 测定 VEGF 分泌、明胶酶谱法测定基质金属蛋白酶（MMPs）活性以及敏感多微孔比色测定法测定 NFKB DNA 结合活性的影响。此外，我们进行了实验研究 aPL 是否会影响体内血管生成在小鼠模型中。我们发现，aPL 显著减少 HEEC 在体外 Matrigel 测定中形成的小管的数量和总长度，并减少 aPL 接种小鼠中新形成的血管。此外，aPL 还显著降低 VEGF 和 MMPs 的产生，并且在核水平上降低 NFKB DNA 结合活性。从我们的结果来看，aPL 与血管生成抑制有关，这表明进一步有额外的机制可以解释 APS 中的胎盘功能不全。
