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

批准号：
7934488
负责人：
DENNIS M. MCNAMARA
金额：
$ 49.98万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7934488
关键词：
Address Area Autoimmunity Biological Markers Biopsy Birth Cardiac Cardiomyopathies Cessation of life Characteristics Chronic Clinical Trials DNA Development Disease Enrollment Etiology Event Frequencies Future Gadolinium Genetic Heart Transplantation Hormonal Hormonal Change Imaging Techniques Immune system Immunologics Inflammation Injury Investigation Left Left Ventricular Dysfunction Left Ventricular Ejection Fraction Magnetic Resonance Imaging Modeling Morbidity - disease rate Mus Myocardial Myocardial dysfunction Myocardium Pathogenesis Patients Postpartum Period Pregnancy Pregnancy Complications Primary idiopathic dilated cardiomyopathy Process Progressive Disease Prolactin Rare Diseases Recovery Research Resolution Serum Staging Testing Time Tissue Banking Tissue Banks Tissues United States Woman immune activation immunoregulation improved innovation mortality patient registry public health relevance theories

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）：该提案解决了挑战领域 7：加强临床试验：07-OD(ORDR)-102，用于开发罕见病遗传患者注册表。围产期心肌病 (PPCM) 是一种妊娠并发症，在美国，新生儿出生比例为 1:1800 至 1:3500，它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最后一个月或产后前五个月出现的原发性心肌功能障碍（LVEF < 0.45），在临床上与其他形式的特发性扩张型心肌病无法区分。尽管其病因尚不清楚，但大多数理论都集中在妊娠和产后期的免疫过程上。六个月内，多达一半的患者心肌功能显着改善，但仍有大量患者患有慢性心肌病，可能进展至死亡或心脏移植。该提案将研究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有关，并且免疫激活时间较长的女性恢复心肌功能的可能性较小。此外，虽然催乳素抑制已作为围产期心肌病小鼠模型的免疫调节手段进行了研究，但产后激素变化与免疫激活的关系仍有待探索。 PPCM 中很少进行心内膜心肌活检；然而，最近磁共振成像（MRI）证实了心肌炎症和损伤。以往对 PPCM 的研究受到研究数量的限制，并且尚未研究心肌损伤程度与 PPCM 随后恢复的关系。该提案将建立一个多中心网络，致力于研究 PPCM 的发病机制，并将建立一个足够规模的生物库，以探索妊娠期激素和细胞事件、全身免疫激活、心肌炎症、PPCM 发展之间的关系。及其分辨率。此外，通过开发新的生物标志物和针对这种疾病的无创评估，这项研究将提高临床医生描绘那些将从慢性心肌病中康复的女性的能力，并为未来 PPCM 的介入试验奠定基础。。。公共卫生相关性：这项研究旨在改善围产期心肌病的治疗方法，围产期心肌病是一种罕见的妊娠并发症，仍然是孕产妇发病和死亡的主要原因。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，以区分那些将从患有更严重的进展性疾病的女性中康复的女性。