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Genetic Analysis of microRNAs Function in Diabetic Cardiomyopathy

糖尿病心肌病中 microRNA 功能的遗传分析

基本信息

批准号：
8495395
负责人：
DJAMEL LEBECHE
金额：
$ 39.94万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-05 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8495395
关键词：
Ablation Accounting Animal Model Animals Binding Sites Bioinformatics Biological Calcium Cardiac Cardiac Myocytes Cardiomyopathies Cardiovascular Abnormalities Cardiovascular Diseases Cell Culture System Clinical Computer Analysis Congenital Heart Defects Congestive Heart Failure Coronary artery Custom Defect Dependovirus Depressed mood Development Diabetes Mellitus Disease Ensure Epidemic Experimental Models Functional disorder Gene Expression Gene Targeting Gene Transfer Genes Goals Heart Heart Diseases Heart Hypertrophy Heart failure Homeostasis Human Hypertrophy Immunity Individual Insulin Insulin Resistance Luciferases Mass Spectrum Analysis Metabolic Metabolism MicroRNAs Molecular Morbidity - disease rate Mus Myocardial Non-Insulin-Dependent Diabetes Mellitus Obesity Pathogenesis Pathway interactions Patients Physiological Play Porifera Prevalence Primary Cell Cultures Proteins Proteomics Rattus Regulation Reporter Risk Factors Role Signal Pathway Stroke Therapeutic Transgenic Mice Untranslated Regions Up-Regulation Ventricular Work base cDNA Arrays diabetic diabetic cardiomyopathy diabetic patient diabetic rat early onset gain of function genetic analysis genome-wide glucose uptake hemodynamics in vitro Assay in vivo interest loss of function mortality mouse model nanoparticle new therapeutic target novel novel strategies overexpression public health relevance response stem therapeutic development transcriptomics type I and type II diabetes vector

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular abnormalities are significant manifestations of diabetes mellitus and account for much of the increased mortality in diabetic patients. It is well recognized that cardiomyopathy occurs frequently in diabetic patients in the absence of known cardiac risk factors. Although several mechanisms have been proposed, the pathogenesis of diabetic cardiomyopathy is not well understood, and the overall complexity of the disease suggests that additional regulatory mechanisms remain to be identified. Recently, a novel paradigm for the role of microRNAs (miRNAs) in cardiac function has emerged. Based on the profound influence of numerous miRNAs in the development of pathological cardiac hypertrophy and development, we hypothesize that diabetic cardiomyopathy is associated with alterations in specific miRNAs that contribute to the pathogenesis of the disease. Our recent work identified miR-152 to be significantly upregulated in human and rat diabetic failing hearts. It is therefore our hypothesis that miR-152 regulates genes involved in cardiac dysfunction associated with diabetic cardiomyopathy and silencing miR-152 in vivo can reserve such abnormalities. Our aim in this proposal is to identify, analyze and functionally elucidate the potential role of miR-152 and its physiological targets and signaling pathways in the setting of diabetes-induced cardiac dysfunction. Our long-term goal is to provide new approaches using miRNA-based therapeutics to treat heart failure in humans. The elucidation of how cardiac miRNAs expression contributes to the development of diabetic cardiomyopathy will be important to interfere with disease-related pathways and may prove valuable as potential therapeutics.

描述（由申请人提供）：心血管异常是糖尿病的重要表现，是糖尿病患者死亡率增加的主要原因。众所周知，心肌病在缺乏已知心脏危险因素的糖尿病患者中频繁发生。虽然已经提出了几种机制，糖尿病心肌病的发病机制还没有得到很好的理解，疾病的整体复杂性表明，其他的调节机制仍有待确定。最近，一个新的范式microRNAs（miRNAs）在心脏功能中的作用已经出现。基于许多miRNAs在病理性心脏肥大和发展中的深远影响，我们假设糖尿病心肌病与特定miRNAs的改变相关，这些miRNAs有助于疾病的发病机制。我们最近的工作确定miR-152在人类和大鼠糖尿病衰竭心脏中显著上调。因此，我们假设miR-152调节与糖尿病性心肌病相关的心功能不全相关的基因，体内沉默miR-152可以保留这些异常。本研究的目的是鉴定、分析和功能性阐明miR-152及其生理靶点和信号通路在糖尿病诱导的心功能不全中的潜在作用。我们的长期目标是提供使用基于miRNA的疗法治疗人类心力衰竭的新方法。阐明心脏miRNAs表达如何促进糖尿病心肌病的发展对于干扰疾病相关通路将是重要的，并可能被证明是有价值的潜在治疗方法。