Complement Activation and Hypertensive Diseases of Pregnancy

补体激活与妊娠高血压疾病

基本信息

批准号：
8243923
负责人：
ANNE M. LYNCH
金额：
$ 22.95万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-27 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8243923
关键词：
Address American Heart Association Antigen-Antibody Complex Antiphospholipid Syndrome Apoptotic Attenuated Biological Markers Blood Vessels Blood specimen Cardiovascular Diseases Cells Chronic Colorado Complement Complement Activation Complement Inactivators Data Databases Decidua Development Disease Enzymes Evaluation Event Exploratory/Developmental Grant Freezing Functional disorder Funding Growth HELLP Syndrome Hemolysis Hospitals Human Hypertension Hypertension induced by pregnancy Immune Immune system Infection Inflammation Inflammatory Life Light Link Literature Liver Longitudinal Studies Marines Maternal Mortality Measures Mediating Medical Mentored Patient-Oriented Research Career Development Award Modeling Morbidity - disease rate Mothers Mus Mutation Natural History Necrosis Neonatal Outcome Pathogenesis Pathway interactions Perinatal Placenta Plasma Platelet Count measurement Play Pre-Eclampsia Pregnancy Pregnancy Outcome Pregnant Women Preventive Intervention Proteins Public Health Recording of previous events Recruitment Activity Reporting Research Research Design Risk Risk Factors Role Sampling Series Testing Therapeutic Time Translating United States National Institutes of Health Universities Variant Vascular Diseases Visit Woman cohort combat complement pathway complement system detector fetal genetic regulatory protein inflammatory marker modifiable risk normotensive novel novel therapeutic intervention pregnant prenatal

项目摘要

DESCRIPTION (provided by applicant): Preeclampsia and gestational hypertension are associated with an increased risk of adverse prenatal outcomes. Altered immune-mediated inflammatory events in the placenta contribute to the pathogenesis of these hypertensive diseases of pregnancy. The complement system, a component of the innate immune system is a series of over 30 proteins that combats infection and removes immune complexes as well as ischemic, necrotic and apoptotic cells. An intact complement system is important in pregnancy. Novel research from marine models of the antiphospholipid antibody syndrome and spontaneous fetal loss has shown that complement activation in the deciduas is a major effectors for both intra-uterine fetal loss and intra-uterine growth restriction. We have translated these important findings into a study in human pregnancy, the Denver Complement Study. This study - the first to examine the role of the complement pathways in early pregnancy - made the important original discovery that elevated levels of complement activation fragments in a single plasma sample drawn at less than 20 weeks' gestation are significantly associated with an increased risk of gestational hypertension and preeclampsia later in pregnancy. In this proposed study we propose to move this research forward to address the important question of the natural history of complement activation fragments measured longitudinally in pregnancy and their links with gestational hypertension-preeclampsia. These questions have not been previously addressed in a prospectively studied pregnant cohort. We have developed the following specific aim: To determine the association between complement activation fragments measured at multiple time points in gestation with subsequent development of hypertensive diseases of pregnancy in a longitudinal study design. We will recruit a cohort of 600 ethnically and racially diverse pregnant women and follow them prospectively during pregnancy with sequential blood samples for the complement activation fragments. This research will identify a new inflammatory marker of hypertensive diseases of pregnancy. If our hypothesis is proven there may be therapeutic implications as several complement inhibitors are now available that target various components of the complement system thus modifying the effects of the inflammatory cascade. PUBLIC HEALTH RELEVANCE: Preeclampsia and gestational hypertension are associated with an increased risk of adverse prenatal outcomes. This project has the potential to identify new complement biomarkers for hypertensive diseases of pregnancy. The results of the study may ultimately hasten the development of new therapeutic interventions for this adverse pregnancy outcome.

描述（由申请人提供）：先兆子痫和妊娠高血压与不良产前结局的风险增加有关。胎盘中免疫介导的炎症事件的改变导致了这些高血压疾病的发病机理。补体系统是先天免疫系统的一个组成部分，是一系列30多种蛋白质，可以打击感染并去除免疫复合物以及缺血性，坏死和凋亡细胞。完整的补体系统在怀孕中很重要。来自抗磷脂抗体综合征和自发胎儿丧失的海洋模型的新研究表明，Deciduas中的补体激活是局内胎儿内胎儿丧失和局内生长限制的主要效应子。我们已经将这些重要的发现转化为丹佛补体研究的人类怀孕研究。这项研究 - 第一个研究补体途径在怀孕初期的作用的研究，这是一个重要的原始发现，即在妊娠不到20周时抽出的单个血浆样本中补体激活片段的水平升高与妊娠后期妊娠期后期妊娠妊娠的妊娠高血压风险增加显着相关。在这项拟议的研究中，我们建议将这项研究转向，以解决在怀孕中纵向测量的补体激活片段的重要问题，及其与妊娠高血压释放症的联系。这些问题以前尚未在前瞻性研究的怀孕人群中解决。我们已经开发了以下具体目的：确定在妊娠中多个时间点测量的补体激活片段与随后在纵向研究设计中的高血压疾病的发展之间的关联。我们将招募600名种族和种族多样化的孕妇，并在怀孕期间前瞻性地跟随她们，并进行顺序的血液样本，用于补体激活片段。这项研究将确定怀孕高血压疾病的新炎症标志。如果证明我们的假设可能存在治疗意义，因为现在可以使用几种补体抑制剂，以靶向补体系统的各种组成部分，从而改变炎症级联的影响。公共卫生相关性：先兆子痫和妊娠高血压与产前不良后果的风险增加有关。该项目有可能确定新的妊娠高血压疾病的补体生物标志物。该研究的结果最终可能会加快这种不良妊娠结局的新治疗干预措施的发展。