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: 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
• 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

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）： 该提案解决了挑战区域7：增强临床试验：07-OD（ORDR）-102用于开发罕见的疾病遗传患者登记处。围产期心肌病（PPCM）是美国1：1800至1：3500出生的妊娠并发症，这仍然是孕产妇发病率和死亡率的主要原因。该疾病被定义为在怀孕最后一个月或产后头五个月内呈现的主要心肌功能障碍（LVEF <0.45），并且与其他形式的特发性扩张性心肌病在临床上没有区别。尽管其病因尚不清楚，但大多数理论都集中在怀孕的免疫学过程和后置时期。在六个月内，多达一半的患者可以看到心肌功能的显着改善，但是大量患者患有慢性心肌病，可以进展为死亡或心脏移植。该提案将研究围绕腹膜心肌病的心肌恢复，以及产后循环环境与其发病机理和分辨率的关系。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，并且免疫激活更长的女性恢复心肌功能的可能性较小。此外，尽管已研究了催乳素抑制作用，以作为腹膜心肌病的鼠模型的免疫调节手段，但后分组后期的激素变化与免疫激活的关系仍有待探索。心内膜活检很少在PPCM中进行；然而，最近通过磁共振成像（MRI）证明了心肌炎症和损伤。先前对PPCM的研究受到研究数量的限制，并且尚未检查心肌损伤与随后恢复PPCM的关系。该提案将开发一个多中心网络，致力于研究PPCM的发病机理，并将建立具有足够大小的生物银行，以允许探索妊娠的激素和细胞事件之间的关系，系统性免疫激活，心肌炎症，PPCM的发展及其分辨率。此外，通过开发新的生物标志物和对这种疾病的无创评估，这项研究将提高临床医生划定那些将从慢性心肌病中恢复的妇女的能力，并为未来的PPCM进行介入介绍。 。 公共卫生相关性： 这项调查旨在改善可用于腹膜心肌病的治疗方法，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理，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渐进疾病的人那里康复的女性。