Endothelial angiotensin II generation induced by placenta-derived factors from preeclampsia.
Endothelial angiotensin II generation induced by placenta-derived factors from preeclampsia.
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DOI：
10.1177/1933719108322432
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Lewis DF
中科院分区：
文献类型：
--
作者：
Wang Y;Gu Y;Lewis DF
对血管紧张素II的超敏反应导致先兆子痫患者血管收缩增加。在这项研究中，我们确定是否胎盘衍生因子可以影响内皮细胞血管紧张素II的产生。我们的研究结果表明，更多的血管紧张素II产生的内皮细胞与先兆子痫胎盘条件培养基比正常条件培养基或未经处理的控制处理的细胞。为了确定哪种途径，血管紧张素转换酶或非血管紧张素转换酶血管紧张素生成酶/糜蛋白酶，可能参与先兆子痫条件培养基诱导的血管紧张素II生成，血管紧张素转换酶抑制剂卡托普利和胰凝乳蛋白酶抑制剂单独或组合应用于细胞培养物。我们发现，糜蛋白酶抑制剂，而不是卡托普利，可以减弱增加血管紧张素II的产生。为了进一步测试蛋白酶对内皮细胞血管紧张素II产生的特异性作用，使内皮细胞在细胞培养插入物中生长，并将胰凝乳蛋白酶加入细胞培养物的上室（顶端暴露）。收集下室（基底方向）中的培养基并测量血管紧张素II。我们的研究结果表明，顶端暴露的内皮细胞的蛋白酶导致浓度依赖性增加血管紧张素II的基础释放。血管紧张素II受体-1的表达也上调先兆子痫条件培养基或糜蛋白酶处理的细胞。这些数据表明，胎盘源性因子可能激活血管内皮细胞中的凝乳酶-血管紧张素途径。此外，响应于蛋白酶刺激而增加的血管紧张素II的内皮细胞基础释放进一步表明循环中的血管紧张素II水平可能不一定反映血管壁内的血管紧张素II产生。
Hypersensitivity to angiotensin II contributes to the increased vasoconstriction in preeclampsia. In this study, we determined whether placenta-derived factors could affect endothelial cell angiotensin II generation. Our results showed that more angiotensin II was produced by endothelial cells treated with preeclampsia placental conditioned medium than the cells treated with normal conditioned medium or untreated controls. To determine which pathway, angiotensin-converting enzyme or nonangiotensin-converting enzyme angiotensin-generating enzyme/chymase, might be involved in preeclampsia conditioned medium induced angiotensin II generation, angiotensin-converting enzyme inhibitor captopril and chymotrypsin inhibitors were applied to the cell culture either separately or in combination. We found that chymotrypsin inhibitor, but not captopril, could attenuate the increased angiotensin II generation. To further test specific effects of the protease on endothelial cell angiotensin II generation, endothelial cells were grown in cell culture inserts and chymotrypsin was added to the upper chamber of the cell culture (apical exposure). The medium in the lower chamber (basal direction) was collected and measured for angiotensin II. Our results showed that apical exposure of endothelial cells to the protease resulted in a concentration-dependent increase in basal release of angiotensin II. Angiotensin II receptor-1 expression was also upregulated in cells treated with preeclampsia conditioned medium or chymotrypsin. This data suggest that placenta-derived factors may activate chymase-angiotensin pathway in endothelial cells. Moreover, increased endothelial cell basal release of angiotensin II in response to the protease stimulation further suggests that angiotensin II levels in the circulation may not necessarily reflect angiotensin II generation within the vascular wall.
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影响因子：
3.8
作者：
Wang, Y;Zhang, Y;Alexander, JS
通讯作者：
Alexander, JS
影响因子：
3.7
作者：
Merrill, DC;Karoly, M;Brosnihan, KB
通讯作者：
Brosnihan, KB
影响因子：
15.9
作者：
GANT, NF;DALEY, GL;MACDONALD, PC
通讯作者：
MACDONALD, PC
影响因子：
2.3
作者：
van Mourik, JA;de Wit, TR;Voorberg, J
通讯作者：
Voorberg, J
DOI：
10.1111/j.1749-6632.1963.tb53698.x
发表时间：
1963-01-01
期刊：
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES
影响因子：
--
作者：
LAGUNOFF, D;BENDITT, EP
通讯作者：
BENDITT, EP