A foundation study of the effects of postnatal enalapril on maternal cardiac function following early-onset pre-eclampsia.

产后依那普利对早发性先兆子痫后母亲心脏功能影响的基础研究。

• 批准号: MR/R001693/1
• 负责人: Laura Ormesher
• 金额: $ 28.73万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR001693%2F1
• 关键词: foundation; study; effects; postnatal; enalapril

BackgroundPre-eclampsia (PE) is a condition in pregnancy, identified by a combination of high blood pressure and protein in the urine. It affects 3-5% of pregnancies and is associated with significant risks to mother and baby. Women with early-onset PE (EPE; onset before 8 months) frequently develop abnormal heart function, which increases their risk of heart disease in later life. Subtle changes in heart function have also been shown to increase the chance of a woman getting PE again in her next pregnancy. Despite this, research to date has focused on the pregnancy and relatively little is known about what happens after pregnancy and whether outcomes can be improved with treatment. sFlt is a protein that prevents blood vessel growth and causes blood vessel constriction. sFlt levels are raised in EPE and correlate with the degree of abnormal heart function. In animal studies, sFlt has been shown to directly cause injury to the heart and it is therefore possible that sFlt mediates EPE associated heart damage. Angiotensin converting enzyme (ACE) inhibitors are commonly used to protect against heart damage following myocardial infarction, but their use has never been tested following EPE. Aims1. Determine the mechanism by which sFlt causes heart injury in EPE.2. Determine whether this can be reversed with ACE inhibitors taken after birth. Objectives 1. To characterise abnormal heart function following EPE and determine if this can be modified by treatment with enalapril.2. To explore the mechanism of sFlt-mediated heart damage in an animal model of PE-like syndrome and determine if it can be ameliorated by PN enalapril treatment. Study designEPE (human) study. Women who have had EPE, will be randomly allocated to enalapril or placebo from delivery for 6 months. Heart function will be assessed using blood tests and ultrasound scans (echocardiography). This will allow us to learn more about how EPE affects the heart (from the placebo group) and measure the protective effect of enalapril on the heart. Animal model study. The effect of sFlt on the heart function of pregnant rats will be tested by comparing markers of heart damage in treated and untreated animals. Following this I will test the disease modifying effects of enalapril after birth in sFlt treated animals using serial blood tests, ultrasound scans of the heart and examination heart using microscopy.ImpactIf successful, this will be the first study to establish an effective treatment for the heart damage caused by EPE and will enable longer term studies in the future. This research will also provide foundations to test alternative treatments in EPE-induced heart disease. Early intervention after pregnancy could serve to reduce PE recurrence and dramatically reduce the long-term consequences of heart disease in this high-risk group of women.

背景先兆子痫（PE）是妊娠期的一种疾病，通过高血压和尿液中蛋白质的联合检测来确定。它影响3-5%的怀孕，并与母亲和婴儿的重大风险有关。早发性PE（EPE;在8个月前发病）的女性经常出现心脏功能异常，这增加了她们在以后生活中患心脏病的风险。心脏功能的细微变化也被证明会增加女性在下次怀孕时再次患PE的机会。尽管如此，迄今为止的研究主要集中在怀孕方面，对怀孕后发生的事情以及治疗是否可以改善结果知之甚少。sFlt是一种阻止血管生长并引起血管收缩的蛋白质。sFlt水平在EPE中升高，并与心脏功能异常的程度相关。在动物研究中，已显示sFlt直接导致心脏损伤，因此sFlt可能介导EPE相关的心脏损伤。血管紧张素转换酶（ACE）抑制剂通常用于防止心肌梗死后的心脏损伤，但它们的使用从未在EPE后进行过测试。目标1.确定sFlt在EPE中引起心脏损伤的机制。确定出生后服用ACE抑制剂是否可以逆转这种情况。目标1.观察EPE后心功能异常，并确定依那普利治疗是否可以改善.在PE样综合征动物模型中探索sFlt介导的心脏损伤机制，并确定PN依那普利治疗是否可以改善该机制。研究设计EPE（人类）研究。患有EPE的妇女将从分娩开始随机分配至依那普利或安慰剂组，持续6个月。将使用血液检查和超声扫描（超声心动图）评估心脏功能。这将使我们能够更多地了解EPE如何影响心脏（从安慰剂组），并测量依那普利对心脏的保护作用。动物模型研究。将通过比较处理和未处理动物的心脏损伤标志物来测试sFlt对妊娠大鼠心脏功能的影响。在此之后，我将测试依那普利的疾病修饰效果出生后sFlt治疗的动物使用系列血液检查，心脏超声扫描和检查心脏使用microscopic.ImpactIf成功，这将是第一个研究，以建立一个有效的治疗EPE引起的心脏损伤，并将使长期的研究在未来。这项研究还将为测试EPE诱导的心脏病的替代治疗提供基础。怀孕后的早期干预可以减少PE复发，并大大减少心脏病的长期后果，在这个高危群体的妇女。

项目成果

Postnatal cardiovascular morbidity following preterm pre-eclampsia: An observational study.

早产先兆子痫后的产后心血管发病率：一项观察性研究。

• DOI: 10.1016/j.preghy.2022.08.007
• 发表时间: 2022
• 期刊: Pregnancy hypertension
• 作者: Ormesher L

Postnatal Enalapril to Improve Cardiovascular Function Following Preterm Preeclampsia (PICk-UP):: A Randomized Double-Blind Placebo-Controlled Feasibility Trial.

• DOI: 10.1161/hypertensionaha.120.15875
• 发表时间: 2020-12
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Ormesher L;Higson S;Luckie M;Roberts SA;Glossop H;Trafford A;Cottrell E;Johnstone ED;Myers JE
• 通讯作者: Myers JE

Prevalence of pre-eclampsia and adverse pregnancy outcomes in women with pre-existing cardiomyopathy: a multi-centre retrospective cohort study.

• DOI: 10.1038/s41598-022-26606-z
• 发表时间: 2023-01-04
• 期刊: Scientific reports
• 影响因子: 4.6