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)： 这项提案涉及挑战领域7：加强临床试验：07-OD(ORDR)-102，用于开发罕见疾病遗传患者登记。围产期心肌病(PPCM)是发生在美国1：1800至1：3500新生儿的妊娠并发症，是导致孕产妇发病率和死亡率的主要原因。本病定义为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&lt；0.45)，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的免疫过程中。多达一半的患者在六个月内心肌功能得到显著改善，但相当数量的患者仍患有慢性心肌病，这种疾病可能会进展到死亡或心脏移植。这项建议将探讨围产期心肌病的心肌恢复情况，以及产后循环环境与其发病机制和缓解的关系。特别是，它将检验这样一种假设，即PPCM中的体液和细胞免疫激活与心肌损伤有关，免疫激活时间越长的女性恢复心肌功能的可能性越小。此外，虽然在围产期心肌病小鼠模型中，催乳素抑制作为一种免疫调节手段已被研究，但产后激素变化与免疫激活的关系仍有待探索。心内膜心肌活检在PPCM中很少进行，然而，最近通过磁共振成像(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，尚未研究心肌损伤程度与随后PPCM恢复的关系。这项提议将建立一个致力于PPCM发病机制研究的多中心网络，并将建立一个足够大的生物库，以允许探索妊娠激素和细胞事件、全身免疫激活、心肌炎症、PPCM的发展及其解决之间的关系。此外，通过开发新的生物标记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确定哪些女性将从慢性心肌病中康复的能力，并为未来PPCM的介入试验奠定基础。。 公共卫生相关性： 这项调查旨在改善围产期心肌病的治疗方法，这是一种罕见的妊娠并发症，仍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记物和成像技术，以区分将从更严重的进展性疾病中康复的女性。