Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies.
Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies.
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DOI：
10.1042/cs20110627
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Leeson P
中科院分区：
文献类型：
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作者：
Davis EF;Newton L;Lewandowski AJ;Lazdam M;Kelly BA;Kyriakou T;Leeson P
先兆子痫越来越多地被认为不仅仅是一种孤立的妊娠疾病。患有先兆子痫的孕妇患心血管疾病的风险增加4倍。有趣的是，受影响怀孕的后代患高血压的风险也会增加，并且晚年中风的风险几乎是其两倍。实验方法来确定先兆子痫的关键特征，负责这种编程的后代心血管健康，或在后代中修改的关键生物学途径，有可能突出新的目标，早期一级预防策略。由于先兆子痫发生在所有怀孕的2-5%中，这些发现与英国多达300万人的当前医疗保健有关。在本论文中，我们回顾了目前的文献，这些文献涉及暴露于先兆子痫的后代中不良心血管编程的潜在机制，考虑了两个主要的研究领域：首先，模拟先兆子痫子宫内环境特征的实验模型，其次，在人类中，子代心血管表型在暴露于先兆子痫后改变。我们比较和对比这两个机构的工作结果，以深入了解相关性的可能关键途径。本综述和分析强调了血管功能长期变化的关键作用，并确定了日益关注的领域，特别是对缺氧的反应，免疫修饰，表观遗传学和子宫内环境中的抗血管生成。
Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2–5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu.