Krikun G, Schatz F, Finlay T, Kadner S, Mesia A, Gerrets R, Lockwood C J
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, 10016, USA.
Biochem Biophys Res Commun. 2000 Aug 18;275(1):159-63. doi: 10.1006/bbrc.2000.3277.
The functional endometrial layer receives the implanting blastocyst, but is sloughed off during menstruation. Angiogenesis regulates growth and repair of cycling human endometrium. While vascular endothelial growth factor initiates angiogenesis, the angiopoietins (Angs) acting via the Tie2 receptor, are key regulators of subsequent angiogenic steps. This study is the first to localize Ang-2 and Tie2 in human endometrium and to study Ang-2 regulation in cultured human endometrial endothelial cells (HEECs). Immunohistochemistry revealed that expression of Ang-2 and Tie2 was absent from the glands, low in stromal cells, and intense in the endothelial cells. In contrast, only weak expression of Ang-1 was detected. The phase of the menstrual cycle did not appear to affect the expression of Ang-2 or Tie2. In vitro studies were carried out utilizing isolated HEECs, the most relevant model for endometrial microvascular biology studies. Both hypoxia and phorbol-myristate-acetate enhanced Ang-2 mRNA levels in HEECs. These results suggest that Ang-2 plays a role in endometrial pathologies complicated by impaired blood flow and inflammation.
功能性子宫内膜层接纳着床的囊胚，但在月经期间会脱落。血管生成调节周期性人类子宫内膜的生长和修复。虽然血管内皮生长因子启动血管生成，但通过Tie2受体起作用的血管生成素（Angs）是后续血管生成步骤的关键调节因子。本研究首次在人类子宫内膜中定位Ang-2和Tie2，并研究培养的人类子宫内膜内皮细胞（HEECs）中Ang-2的调节。免疫组织化学显示，Ang-2和Tie2在腺体中无表达，在基质细胞中表达较低，而在内皮细胞中表达强烈。相比之下，仅检测到Ang-1的弱表达。月经周期阶段似乎不影响Ang-2或Tie2的表达。利用分离的HEECs进行了体外研究，这是子宫内膜微血管生物学研究最相关的模型。缺氧和佛波醇-肉豆蔻酸酯-乙酸盐均增强了HEECs中Ang-2 mRNA水平。这些结果表明，Ang-2在伴有血流受损和炎症的子宫内膜病变中起作用。
