The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre-eclampsia
The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre-eclampsia
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DOI：
10.1111/j.1471-0528.2004.00223.x
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发表时间：
2004-09-01
影响因子：
5.8
通讯作者：
Davidge, ST
中科院分区：
文献类型：
--
作者：
Merchant, SJ;Davidge, ST
目的(1)探讨未妊娠、正常妊娠和子痫前期妇女血浆对肌原性张力和内皮依赖性舒张的影响；(2)探讨基质金属蛋白酶（MMPs）在这些血管功能参数中的作用。设计分析未妊娠、正常妊娠和子痫前期妇女血浆对肌原性张力和内皮依赖性松弛的影响，以及MMP抑制对这些参数的影响。加拿大艾伯塔省埃德蒙顿市阿尔伯塔大学。收集了来自非孕妇（n = 9）、正常孕妇（n = 6）和先兆子痫妇女（n = 12）的血浆。方法将C57BL/6J雌性小鼠的肠系膜动脉暴露于未妊娠、正常妊娠和子痫前期妇女的血浆中，在GM6001 （5 muM； MMP抑制剂）缺失和存在的情况下，评估动脉功能。主要观察指标为肌原性张力和内皮依赖性松弛。结果子痫前期妇女的血浆和未怀孕妇女的血浆在压力大于或等于70 mmHg时显著增强肌原性张力（P < 0.001），使离体动脉对甲胆碱的最大松弛减弱（P < 0.001; P < 0.005）。GM6001仅在暴露于子痫前期妇女血浆的血管中改变反应；然而，与我们的假设相反，这进一步增强了肌张力，进一步废除了松弛。结论：未怀孕妇女和子痫前期妇女血浆中培养的血管功能特征惊人地相似，这表明子痫前期可能部分是由于缺乏对妊娠的必要适应。然而，尽管存在这些相似之处，但MMP抑制的效果不同，这表明与未怀孕和正常孕妇相比，MMPs在子痫前期妇女的血管系统中发挥更大的作用。
Objectives (1) To investigate the effects of plasma from non-pregnant, normal pregnant and pre-eclamptic women on myogenic tone and endothelium-dependent relaxation; (2) To investigate the role of matrix metalloproteinases (MMPs) in these parameters of vascular function.Design Analysis of the effects of plasma from non-pregnant, normal pregnant and pre-eclamptic women on myogenic tone and endothelium-dependent relaxation, and the effects of MMP inhibition on these parameters.Setting University of Alberta, Edmonton, Alberta, Canada.Samples Pooled plasma from non-pregnant (n = 9), normal pregnant (n = 6) and pre-eclamptic women (n = 12).Methods Mesenteric arteries from virgin female C57BL/6J mice were exposed to pooled plasma from nonpregnant, normal pregnant and pre-eclamptic women in the absence and presence of GM6001 (5 muM; MMP inhibitor), and arterial function was assessed.Main outcome measures Myogenic tone and endothelium-dependent relaxation.Results Plasma of women with pre-eclampsia, and interestingly, plasma of non-pregnant women, significantly enhanced myogenic tone at pressures greater than or equal to70 mmHg (P < 0.001) and blunted the maximum relaxation to methacholine (P < 0.001; P < 0.005) in isolated arteries. GM6001 altered response only in vessels exposed to the plasma of women with pre-eclampsia; however, contrary to our hypothesis, this further enhanced myogenic tone and further abrogated relaxation.Conclusions The strikingly similar vascular function profiles of vessels incubated in the plasma of nonpregnant and pre-eclamptic women suggest that pre-eclampsia may be due, in part, to the lack of a necessary adaptation to pregnancy. Despite these similarities, however, there are differential effects of MMP inhibition, suggesting that MMPs play a greater role in the vasculature of women with pre-eclampsia compared with non-pregnant and normal pregnant women.