Prognostic Significance of microRNA Expression in Children with Cardiomyopathy

microRNA 表达在儿童心肌病中的预后意义

• 批准号: 9907570
• 负责人: STEVEN EDWARD LIPSHULTZ
• 金额: $ 89.84万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-17 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907570
• 关键词: 1 year old; Acute; Address; Adult; Binding; Biological Markers; Blood; Blood Tests; Canada; Cardiomyopathies; Cardiovascular Diseases; Cells; Cessation of life; Child; Childhood; Chronic; Clinical; Clinical Treatment; Decision Making; Development; Diagnosis; Dilated Cardiomyopathy; Disease; Disease Outcome; Enrollment; Etiology; Expression Profiling; Functional disorder; Funding; Future; Gene Expression; Genes; Goals; Graft Survival; Heart; Heart Transplantation; Heart failure; Incidence; Investigation; Malignant Neoplasms; Measurement; Mechanics; Medical; Methodology; MicroRNAs; National Heart, Lung, and Blood Institute; Nucleotides; Outcome; Patients; Pattern; Pediatric Cardiomyopathy; Population; Positioning Attribute; Proteins; Publishing; RNA; Recovery; Registries; Research Personnel; Resolution; Restrictive Cardiomyopathy; Retrospective Studies; Risk stratification; Sampling; Serum; Systolic heart failure; Time; Tissues; Transplant Recipients; Transplantation; Untranslated RNA; Ventricular; Ventricular Function; Work; base; biobank; circulating microRNA; cohort; epidemiologic data; experience; improved; insight; member; microvesicles; new therapeutic target; novel; outcome prediction; pediatric cardiologist; pediatric heart failure; primary endpoint; prognostic; prognostic significance; programs; prospective; treatment planning

Project Summary Pediatric cardiomyopathies encompass a heterogeneous group of disorders including dilated, hypertrophic, and less commonly, restrictive cardiomyopathies. Emerging experimental evidence and epidemiologic data suggest that the pediatric heart failure population is distinctly different from adult patients The most common cause of heart failure and reason for cardiac transplantation in children older than 1 year is dilated cardiomyopathy (DCAmong these etiologies, pediatric dilated cardiomyopathy (DCM) has an estimated 40% five year transplant-free survival and remains the most common diagnosis leading to heart transplant in children greater than 1 year of age. The central hypothesis is that circulating microRNAs (miRs) will be useful biomarkers for risk stratification, will correlate with outcomes and may represent novel therapeutic targets in children with DCM. The aims of this study are: 1) Determine the profile of circulating miRs in a cohort of children with DCM and acute systolic heart failure. The circulating miR expression patterns will then be stratified based on reaching a primary end-point by 1 year defined as: [1] death or transplantation, [2] recovery (normalization of ventricular size and function) or [3] stable DCM (persistent ventricular dilation or dysfunction); 2) Define the miR profile in a separate cohort of children with chronic, stable DCM to determine if those patients with stable DCM who progress to death/transplant within 1 year will be similar to the profile of the Aim 1 cohort of children with acute heart failure who also progress to death/transplant; and 3) Analyze the expression of circulating and heart tissue miRs in pediatric controls (non-failing donors whose heart could not be placed [NF]) and pediatric DCM patients. The results of this study could improve clinicians prognostic’ assessment at diagnosis of DCM in children, improve decision-making regarding listing children for heart transplant as opposed to identifying those who are expected to recover ventricular function, and could provide insight into cellular mechanisms of disease and define novel targets for future treatment of DCM in children.

项目概要 小儿心肌病涵盖一组异质性疾病，包括扩张型、肥厚型、 较少见的是限制性心肌病。新出现的实验证据和流行病学数据 表明儿童心力衰竭人群与成人患者明显不同 1岁以上儿童心力衰竭的原因和心脏移植的原因扩大 心肌病（DC 在这些病因中，小儿扩张型心肌病 (DCM) 估计占 40% 五年无移植生存率仍然是导致心脏移植的最常见诊断 1岁以上的儿童。核心假设是循环的 microRNA (miR) 将会有用 用于风险分层的生物标志物，将与结果相关，并可能代表新的治疗靶点 患有 DCM 的儿童。本研究的目的是：1) 确定一组循环 miR 的概况 患有 DCM 和急性收缩性心力衰竭的儿童。循环的 miR 表达模式将是 根据 1 年达到主要终点进行分层，定义为：[1] 死亡或移植，[2] 康复 （心室大小和功能正常化）或 [3] 稳定 DCM（持续性心室扩张或功能障碍）； 2) 在患有慢性、稳定 DCM 的单独队列中定义 miR 谱，以确定这些儿童是否 患有稳定 DCM 的患者在 1 年内进展至死亡/移植将与 Aim 的情况相似 1 组患有急性心力衰竭且也进展至死亡/移植的儿童； 3）分析 儿科对照（心脏不能衰竭的非衰竭供体）中循环和心脏组织 miR 的表达 被放置[NF]）和儿科 DCM 患者。这项研究的结果可以改善临床医生的预后” 儿童扩张型心肌病诊断时的评估，改善将儿童列入心脏疾病名单的决策 移植而不是识别那些有望恢复心室功能的人，并且可以提供 深入了解疾病的细胞机制，并确定未来儿童 DCM 治疗的新靶标。