Aspirin to prevent cardiac dysfunction in preeclampsia

阿司匹林预防子痫前期心功能障碍

• 批准号: 10321956
• 负责人: Sajid Shahul
• 金额: $ 68.7万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10321956
• 关键词: Activin A type II receptor; Activins; Affect; Aging; Animal Model; Aspirin; Back; Basic Science; Binding; Blood; Cardiac; Cardiac development; Cardiovascular Diseases; Cardiovascular system; Cell surface; Cells; Cessation of life; Clinical; Clinical Trials; Data; Development; Disease; Family; Fibrosis; Functional disorder; Future; Glycoproteins; Growth Factor; Heart; Heart failure; Heparitin Sulfate; Human; Hybrids; Hypertension; Incidence; Inflammatory; Infusion procedures; Interdisciplinary Study; Investigation; Knowledge; Late pregnancy; Lead; Measures; Mediating; Meta-Analysis; Methodology; Modeling; Molecular; Molecular Target; Morbidity - disease rate; Myocardial Ischemia; Myocardial dysfunction; Organ; Outcome; Pathology; Pathway interactions; Patients; Perfusion; Perinatal; Pharmaceutical Preparations; Placebos; Placenta; Plasma; Postpartum Period; Pre-Clinical Model; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnant Women; Prevention; Public Health; Randomized; Randomized Controlled Trials; Rattus; Recording of previous events; Research; Risk Factors; Second Pregnancy Trimester; Signal Transduction; Systolic heart failure; Testing; Transforming Growth Factor beta; United States; Uterus; Woman; activin A; antagonist; base; cardiogenesis; cell type; coronary fibrosis; double-blind placebo controlled trial; experimental study; heart function; heparanase; improved; innovation; macrophage; medical complication; member; mortality; novel; postpartum complications; pregnant; pressure; prevent; randomized trial

ABSTRACT Preeclampsia (PE) is a disease of late pregnancy characterized by hypertension and organ damage, which not only increases peripartum morbidity but is associated with the postpartum development of heart failure, including myocardial fibrosis and systolic heart failure. Despite two decades of research demonstrating this association and a large public health burden, the molecular mechanisms mediating PE-induced postpartum heart failure remain poorly understood and therapies to prevent this outcome are lacking. One potential trigger may be the profibrotic growth factor Activin A, a member of the transforming growth factor beta family produced by the placenta and inflammatory cells. Using a randomized mechanistic clinical trial of aspirin vs. placebo for patients with preeclampsia, integrated with studies of the mechanisms by which aspirin and Activin A might affect the heart, we will dramatically advance knowledge of cardiac dysfunction in preeclampsia and its possible treatments. We pursue two specific aims to answer these questions. AIM 1 is a randomized trial to test whether aspirin improves cardiac function and decreases Activin A in women with preeclampsia. AIM 2 Identifies how increased plasma Activin A during pregnancy causes postpartum cardiac dysfunction and how aspirin prevents it. This project innovates methodologically and at the bench in order to dramatically advance our understanding of a major cause of morbidity and mortality in women globally.

摘要 子痫前期(PE)是妊娠晚期的一种疾病，以高血压和器官损害为特征，而不是 只会增加围产期的发病率，但与产后心力衰竭的发展有关， 包括心肌纤维化和收缩性心力衰竭。尽管二十年的研究证明了这一点 协会与巨大的公共卫生负担，介导产后PE的分子机制 心力衰竭仍然知之甚少，缺乏预防这种结果的治疗方法。一个潜在的触发因素 可能是促纤维化生长因子激活素A，转化生长因子β家族的成员 由胎盘和炎症细胞产生。 使用阿司匹林与安慰剂治疗子痫前期患者的随机、机械性临床试验 随着对阿司匹林和激活素A可能影响心脏的机制的研究，我们将极大地 先兆子痫患者心功能障碍及其可能的治疗方法的研究进展。我们追求的是两个具体的 旨在回答这些问题。目标1是一项测试阿司匹林是否能改善心脏功能的随机试验 并降低先兆子痫妇女的激活素A水平。目标2确定血浆激活素A是如何在 怀孕会导致产后心脏功能障碍，以及阿司匹林是如何预防的。该项目具有创新性 在方法论上和在法官席上，以极大地促进我们对 全球妇女发病率和死亡率。