Immune Activation and Myocardial Recovery in Peripartum Cardiomyopathy

围产期心肌病的免疫激活和心肌恢复

基本信息

项目摘要

DESCRIPTION (provided by applicant): This proposal addresses Challenge area 7: Enhancing Clinical Trials: 07-OD(ORDR)-102 for the development of a rare disease genetic patient registry. Peripartum cardiomyopathy (PPCM) is a complication of pregnancy occurring in 1:1800 to 1:3500 births in the United States which remains a major cause of maternal morbidity and mortality. This disorder is defined as a primary myocardial dysfunction (LVEF < 0.45) presenting in the last month of pregnancy or in the first five months post-partum and is clinically indistinguishable from other forms of idiopathic dilated cardiomyopathy. Though its etiology remains unknown, most theories have focused on the immunologic processes of pregnancy and the post partum period. Significant improvement in myocardial function is seen in up to half of patients within six months, but a significant number of patients are left with chronic cardiomyopathy which can progress toward death or cardiac transplantation. This proposal will investigate myocardial recovery in peripartum cardiomyopathy, and the relationship of the postpartum circulating milieu to its pathogenesis and resolution. In particular, it will test the hypothesis that humoral and cellular immune activation in PPCM is associated with myocardial injury and that women with more prolonged immune activation are less likely to recover myocardial function. In addition while prolactin inhibition has been investigated in as a means of immune modulation in murine models of peripartum cardiomyopathy, the relationship of hormonal changes of the post partum period to immune activation remains to be explored. Endomyocardial biopsy is rarely performed in PPCM; however, myocardial inflammation and injury have been demonstrated recently by magnetic resonance imaging (MRI). Previous studies of PPCM have been limited by study number, and the relationship of the extent of myocardial injury to subsequent recovery of PPCM has not been examined. This proposal will develop a multicenter network dedicated to research into the pathogenesis of PPCM and will establish a biologic bank of sufficient size to allow the exploration of the relationships between hormonal and cellular events of pregnancy, systemic immune activation, myocardial inflammation, the development of PPCM and its resolution. In addition, through the development of new biomarkers and noninvasive assessment for this disorder, this investigation will improve the ability of clinicians to delineate those women who will recover from those who will be left with chronic cardiomyopathy and set the stage for future interventional trials in PPCM. . Public Health Relevance: This investigation seeks to improve the treatments available for peripartum cardiomyopathy, a rare complication of pregnancy which remains a major cause of maternal morbidity and mortality. The proposal will establish a multicenter network dedicated to understanding the pathogenesis of this disorder and to developing new innovative biomarkers and imaging techniques to differentiate women who will recover from those with more serious progressive disease.
描述(由申请人提供): 本提案涉及挑战领域7:加强临床试验:07-OD(ORR)-102,用于开发罕见病遗传患者登记。围产期心肌病(PPCM)是一种妊娠并发症,在美国发生率为1:1800至1:3500,仍然是孕产妇发病和死亡的主要原因。这种疾病被定义为在妊娠的最后一个月或产后的前五个月出现的原发性心肌功能障碍(LVEF < 0.45),并且在临床上与其他形式的特发性扩张型心肌病难以区分。虽然其病因仍然不明,但大多数理论都集中在怀孕和产后期间的免疫过程。多达一半的患者在六个月内心肌功能显著改善,但大量患者患有慢性心肌病,可能会发展为死亡或心脏移植。本研究将探讨围产期心肌病的心肌恢复,以及产后循环环境与其发病机制和解决方案的关系。特别是,它将检验以下假设:PPCM中的体液和细胞免疫激活与心肌损伤相关,并且免疫激活时间更长的女性不太可能恢复心肌功能。此外,虽然已在围产期心肌病小鼠模型中研究了催乳素抑制作为免疫调节的一种手段,但产后激素变化与免疫激活的关系仍有待探索。PPCM很少进行肌内膜活检,但是最近磁共振成像(MRI)显示了心肌炎症和损伤。以前的PPCM研究受到研究数量的限制,心肌损伤程度与随后PPCM恢复的关系尚未得到研究。该提案将开发一个多中心网络,致力于研究PPCM的发病机制,并将建立一个足够大的生物库,以探索妊娠激素和细胞事件,全身免疫激活,心肌炎症,PPCM的发展及其解决方案之间的关系。此外,通过开发新的生物标志物和对这种疾病的非侵入性评估,这项研究将提高临床医生的能力,以描述那些将从慢性心肌病患者中恢复的女性,并为未来PPCM的干预性试验奠定基础。. 公共卫生相关性: 这项调查旨在改善围产期心肌病的治疗,这是一种罕见的妊娠并发症,仍然是孕产妇发病率和死亡率的主要原因。该提案将建立一个多中心网络,致力于了解这种疾病的发病机制,并开发新的创新生物标志物和成像技术,以区分将从更严重的疾病进展中恢复的妇女。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

DENNIS M. MCNAMARA其他文献

DENNIS M. MCNAMARA的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('DENNIS M. MCNAMARA', 18)}}的其他基金

(1/2) Randomized Evaluation of Bromocriptine in Myocardial Recovery Therapy for Peripartum Cardiomyopathy (REBIRTH)
(1/2) 溴隐亭治疗围产期心肌病(REBIRTH)心肌恢复治疗的随机评价
  • 批准号:
    10704072
  • 财政年份:
    2021
  • 资助金额:
    $ 49.98万
  • 项目类别:
(1/2) Randomized Evaluation of Bromocriptine in Myocardial Recovery Therapy for Peripartum Cardiomyopathy (REBIRTH)
(1/2) 溴隐亭治疗围产期心肌病(REBIRTH)心肌恢复治疗的随机评价
  • 批准号:
    10449415
  • 财政年份:
    2021
  • 资助金额:
    $ 49.98万
  • 项目类别:
(1/2) Randomized Evaluation of Bromocriptine in Myocardial Recovery Therapy for Peripartum Cardiomyopathy (REBIRTH)
(1/2) 溴隐亭治疗围产期心肌病(REBIRTH)心肌恢复治疗的随机评价
  • 批准号:
    10214144
  • 财政年份:
    2021
  • 资助金额:
    $ 49.98万
  • 项目类别:
Genomic Analysis of Enhanced Response to Heart Failure Therapy in African America
非洲裔美国人对心力衰竭治疗增强反应的基因组分析
  • 批准号:
    9265711
  • 财政年份:
    2014
  • 资助金额:
    $ 49.98万
  • 项目类别:
Genomic Analysis of Enhanced Response to Heart Failure Therapy in African America
非洲裔美国人对心力衰竭治疗增强反应的基因组分析
  • 批准号:
    8776074
  • 财政年份:
    2014
  • 资助金额:
    $ 49.98万
  • 项目类别:
Immune Activation and Myocardial Recovery in Peripartum Cardiomyopathy
围产期心肌病的免疫激活和心肌恢复
  • 批准号:
    7821933
  • 财政年份:
    2009
  • 资助金额:
    $ 49.98万
  • 项目类别:
Genetic Modulation of Left Ventricular Recovery
左心室恢复的基因调节
  • 批准号:
    7325703
  • 财政年份:
    2003
  • 资助金额:
    $ 49.98万
  • 项目类别:
Genetic Modulation of Left Ventricular Recovery
左心室恢复的基因调节
  • 批准号:
    6704336
  • 财政年份:
    2003
  • 资助金额:
    $ 49.98万
  • 项目类别:
Genetic Modulation of Left Ventricular Recovery
左心室恢复的基因调节
  • 批准号:
    7144480
  • 财政年份:
    2003
  • 资助金额:
    $ 49.98万
  • 项目类别:
Genetic Modulation of Left Ventricular Recovery
左心室恢复的基因调节
  • 批准号:
    6982808
  • 财政年份:
    2003
  • 资助金额:
    $ 49.98万
  • 项目类别:

相似国自然基金

层出镰刀菌氮代谢调控因子AreA 介导伏马菌素 FB1 生物合成的作用机理
  • 批准号:
    2021JJ40433
  • 批准年份:
    2021
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
寄主诱导梢腐病菌AreA和CYP51基因沉默增强甘蔗抗病性机制解析
  • 批准号:
    32001603
  • 批准年份:
    2020
  • 资助金额:
    24.0 万元
  • 项目类别:
    青年科学基金项目
AREA国际经济模型的移植.改进和应用
  • 批准号:
    18870435
  • 批准年份:
    1988
  • 资助金额:
    2.0 万元
  • 项目类别:
    面上项目

相似海外基金

Onboarding Rural Area Mathematics and Physical Science Scholars
农村地区数学和物理科学学者的入职
  • 批准号:
    2322614
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Standard Grant
TRACK-UK: Synthesized Census and Small Area Statistics for Transport and Energy
TRACK-UK:交通和能源综合人口普查和小区域统计
  • 批准号:
    ES/Z50290X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Research Grant
Wide-area low-cost sustainable ocean temperature and velocity structure extraction using distributed fibre optic sensing within legacy seafloor cables
使用传统海底电缆中的分布式光纤传感进行广域低成本可持续海洋温度和速度结构提取
  • 批准号:
    NE/Y003365/1
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Research Grant
Point-scanning confocal with area detector
点扫描共焦与区域检测器
  • 批准号:
    534092360
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Major Research Instrumentation
Collaborative Research: Scalable Manufacturing of Large-Area Thin Films of Metal-Organic Frameworks for Separations Applications
合作研究:用于分离应用的大面积金属有机框架薄膜的可扩展制造
  • 批准号:
    2326714
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Standard Grant
Collaborative Research: Scalable Manufacturing of Large-Area Thin Films of Metal-Organic Frameworks for Separations Applications
合作研究:用于分离应用的大面积金属有机框架薄膜的可扩展制造
  • 批准号:
    2326713
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Standard Grant
Unlicensed Low-Power Wide Area Networks for Location-based Services
用于基于位置的服务的免许可低功耗广域网
  • 批准号:
    24K20765
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
RAPID: Collaborative Research: Multifaceted Data Collection on the Aftermath of the March 26, 2024 Francis Scott Key Bridge Collapse in the DC-Maryland-Virginia Area
RAPID:协作研究:2024 年 3 月 26 日 DC-马里兰-弗吉尼亚地区 Francis Scott Key 大桥倒塌事故后果的多方面数据收集
  • 批准号:
    2427233
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Standard Grant
Postdoctoral Fellowship: OPP-PRF: Tracking Long-Term Changes in Lake Area across the Arctic
博士后奖学金:OPP-PRF:追踪北极地区湖泊面积的长期变化
  • 批准号:
    2317873
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Standard Grant
RAPID: Collaborative Research: Multifaceted Data Collection on the Aftermath of the March 26, 2024 Francis Scott Key Bridge Collapse in the DC-Maryland-Virginia Area
RAPID:协作研究:2024 年 3 月 26 日 DC-马里兰-弗吉尼亚地区 Francis Scott Key 大桥倒塌事故后果的多方面数据收集
  • 批准号:
    2427232
  • 财政年份:
    2024
  • 资助金额:
    $ 49.98万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了