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Epigenomic signaling and heart failure.

表观基因组信号和心力衰竭。

基本信息

批准号：
10310475
负责人：
Jiang Chang
金额：
$ 48.58万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-06 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10310475
关键词：
ATAC-seq Age Aging Angioplasty Animal Genetics Animal Model Animals Antibodies Attenuated Bioinformatics Biological Assay Cardiac Cardiac Myocytes Cardiomegaly Cell Death Signaling Process ChIP-seq Chromatin DNA Methylation DNA Modification Methylases DNA Polymerase II DNA-Directed RNA Polymerase DNMT3B gene Data Dependovirus Development Dilated Cardiomyopathy Down-Regulation Epigenetic Process Event Exhibits Exons Failure Functional disorder Gene Expression Profile Genes Genetic Transcription Genetic Translation Goals Heart Heart Hypertrophy Heart failure High-Throughput Nucleotide Sequencing Histone H3 Human Hypertrophy Impairment Knock-out Knockout Mice Lead Left Lysine Maps Measurement Measures Mediating Medicine Modernization Modification Molecular Molecular Biology Mus Myocardial Infarction Necrosis Pathogenesis Pathologic Processes Pathway Analysis Pathway interactions Patients Pharmacological Treatment Phenotype Prevalence Prevention Prognosis Regulation Repression Research Personnel Resistance Resolution Role SET Domain Signal Transduction Signs and Symptoms Stress Technology Testing Time Tissues Transcript Transcription Initiation Transcription Initiation Site Transcriptional Activation Transgenic Mice Transposase Treatment Failure Vascular blood supply Ventricular Wild Type Mouse aging population base cardiogenesis chromatin immunoprecipitation cohort constriction epigenomics experimental study gain of function genome-wide heart function high throughput screening histone methylation improved insight mortality mouse model myocardial damage new therapeutic target next generation next generation sequencing novel novel therapeutic intervention overexpression pressure prevent recruit ribosome profiling transcriptome sequencing

项目摘要

PROJECT DESCRIPTION/ABSTRACT Heart failure is characterized by a relentless progression of signs and symptoms. A relatively long interval (several years) exists between the precipitating events that induce myocardial damage followed by a functional compensated period and the final state termed dilated cardiomyopathy. Dilated cardiomyopathy is characterized by markedly enlarged heart chambers and impaired contractile function. Delineating the molecular and cellular mechanisms that initiate and mediate the pathogenesis of heart failure during this long interval still remains an enormous challenge, and is the long- term goal of the project. A commonly accepted paradigm for the development of heart failure divides the pathological process into two distinct stages: initial compensatory hypertrophy to keep up with the body demand for blood supply, followed by a critical transition to decompensated failure under persistent stress. Epigenomic regulation is emerging as a new mechanism contributing to the initiation, development and prognosis of heart failure, and next-generation sequencing technologies have made it possible to dissect this complicated regulatory mechanism. In this study, the investigators started with a set of unbiased genome-scale high-throughput screenings in both human and animal failing hearts, and uncovered several potential epigenetic regulators that might be critical for the progression of heart failure including initial stage of cardiac hypertrophy and the later failing stage. A set of comprehensive bioinformatics analyses, molecular biology experiments and genetic animal models are applied to investigate this new mechanism. The eventual results will allow a look from a different angle to understand the progression of HF. The manipulation of the uncovered mechanism could be a novel therapeutic strategy for the heart failure treatment in patients.

项目描述/文摘