Prognostic Significance of microRNA Expression in Children with Cardiomyopathy

项目摘要 儿童心肌病包括一组不同种类的疾病，包括扩张型，肥厚型， 而不太常见的是限制性心肌病。新出现的实验证据和流行病学数据 提示小儿心力衰竭人群明显不同于成人患者最常见 1岁以上儿童心力衰竭和心脏移植的原因扩大 心肌病(DCM)在这些病因中，儿童扩张型心肌病(DCM)估计有40% 五年无移植存活，仍然是导致心脏移植的最常见诊断 1岁以上的儿童。中心假设是循环中的microRNAs(MiRs)将是有用的 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 患有扩张型心肌炎的儿童。这项研究的目的是：1)确定在一个队列中循环的MIR的概况 患有扩张型心肌炎和急性收缩性心力衰竭的儿童。然后循环的miR表达模式将是 根据达到主要终点的1年进行分层，定义为：[1]死亡或移植，[2]恢复 (脑室大小和功能正常化)或[3]稳定的DCM(持续的脑室扩张或功能障碍)； 2)在一组慢性、稳定的DCM儿童中定义miR谱，以确定这些 病情稳定的扩张型心肌病患者在1年内进展至死亡/移植，将与目标相似。 1个同样进展为死亡/移植的急性心力衰竭儿童的队列；以及3)分析 循环和心脏组织miRs在儿科对照组(心脏功能不全的非衰竭供者)中的表达 被放置[nf])和儿童扩张型心肌病患者。这项研究的结果可以改善临床医生的预后。 对儿童扩张型心肌炎的诊断进行评估，改善将儿童列入心脏手术的决策 移植，而不是确定哪些人有望恢复心功能，并可能提供 洞察疾病的细胞机制，并为未来儿童扩张性心肌病的治疗确定新的目标。

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.