Lee Kyung-Ju, Kim Meyoung-Kon, Park Yoon-Hee, Seol Hyun-Joo, Lim Ji-Eun, Lee Jeong No, Oh Min-Jeong
Department of Obstetrics and Gynecology, College of Medicine, Pochon CHA University, Pochon, Kyunggi, Korea.
Hypertens Pregnancy. 2007;26(2):189-99. doi: 10.1080/10641950701204604.
To investigate the mechanism of vascular endothelial growth factor (VEGF)-induced endothelin-1 production in human umbilical vein endothelial cells (HUVECs).
Endothelin-1 levels were measured in conditioned medium of women with preeclampsia HUVECs were treated with different concentrations of VEGF(165) and at various time intervals. Next, we measured endothelin-1 levels after HUVECs were also incubated with VEGF and endothelin-converting enzyme-1 (ECE-1) inhibitor or tissue inhibitors of matrix metalloproteinase-2 (TIMP-2). Additionally, the circulating levels of total and free VEGF, matrix metalloproteinase-2 (MMP-2), and endothelin-1 were measured in 20 preeclamptic patients and 20 healthy pregnant controls.
HUVECs treated with VEGF increased their endothelin-1 production in a concentration and time-dependent manner. The production of endothelin-1 was inhibited by TIMP-2, but not by the ECE-1 inhibitor. Total VEGF, MMP-2, and endothelin-1 concentrations were higher in preeclampsia and showed significant positive correlations between them.
These findings suggest that VEGF-induced endothelin-1 production might be mediated by MMP-2 rather than by ECE-1 upregulation.
研究血管内皮生长因子（VEGF）诱导人脐静脉内皮细胞（HUVECs）产生内皮素-1的机制。
检测子痫前期患者条件培养基中的内皮素-1水平，用不同浓度的VEGF(165)在不同时间间隔处理HUVECs。接下来，在HUVECs与VEGF和内皮素转换酶-1（ECE-1）抑制剂或基质金属蛋白酶-2组织抑制剂（TIMP-2）共同孵育后，我们检测内皮素-1水平。此外，还检测了20例子痫前期患者和20例健康孕妇对照组中总VEGF、基质金属蛋白酶-2（MMP-2）和内皮素-1的循环水平。
用VEGF处理的HUVECs以浓度和时间依赖性方式增加其内皮素-1的产生。内皮素-1的产生受到TIMP-2的抑制，但不受ECE-1抑制剂的抑制。子痫前期患者的总VEGF、MMP-2和内皮素-1浓度较高，且它们之间存在显著的正相关。
这些发现表明，VEGF诱导的内皮素-1产生可能是由MMP-2介导的，而不是由ECE-1上调介导的。
