Epigenomic signaling and heart failure.

表观基因组信号和心力衰竭。

基本信息

批准号：
10528446
负责人：
Jiang Chang
金额：
$ 48.73万
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 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10528446
关键词：
Age Angioplasty Animal Genetics Animal Model Animals Antibodies Attenuated Bioinformatics Biological Assay Cardiac Cardiac Myocytes Cardiomegaly Cell Death Signaling Process Chromatin Compensation DNA Methylation DNA Modification Methylases DNMT3B gene Data Dependovirus Deterioration Development Dilated Cardiomyopathy Down-Regulation Epigenetic Process Event Exhibits Exons Failure Functional disorder Gene Expression Profile Genes Genetic Transcription Goals Heart Heart Hypertrophy Heart failure High-Throughput Nucleotide Sequencing Histone H3 Human Hypertrophy Impairment Knock-out Knockout Mice Left Lysine Maps Measurement Measures Mediating Medicine Methylation Modernization Modification Molecular Molecular Biology Mus Myocardial Infarction Necrosis Pathogenesis Pathologic Processes Pathway Analysis Pathway interactions Patients Peptides Pharmacological Treatment Phenotype Polymerase Prevalence Prevention Prognosis RNA Polymerase II 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 aorta constriction base chromatin immunoprecipitation cohort comparison control epigenomics experimental study gain of function genome-wide heart function high throughput screening histone methylation improved insight mRNA Translation 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/摘要心力衰竭的特征是体征和症状的不断发展。间隔相对较长（几个几年）存在着诱发心肌损伤的降水事件，然后是功能补偿时期和最终状态称为扩张的心肌病。扩张的心肌病的特征是明显扩大心房和收缩功能受损。描述启动和细胞的分子和细胞机制在这个长时间间隔内介导心力衰竭的发病机理仍然是一个巨大的挑战，是长期的该项目的术语目标。心力衰竭发展的普遍接受的范式将病理过程分为两个不同的阶段：初始补偿性肥大以跟上身体对血液供应的需求，其次是关键过渡到持续压力下的失败失败。表观基因组调节正在成为一种新机制，有助于启动，发展和预后心力衰竭和下一代测序技术使得剖析这种复杂的调节机制。在这项研究中，研究人员从两个人类的一组无偏的基因组尺度的高通量筛选开始动物的心脏失败，并发现了可能对进展至关重要的几个潜在的表观遗传调节剂心力衰竭，包括心脏肥大的初始阶段和后来的失败阶段。一组综合生物信息学分析，分子生物学实验和遗传动物模型用于研究这一新的机制。最终的结果将允许从不同角度看，以了解HF的进展。这操纵未覆盖的机制可能是患者心力衰竭治疗的一种新型治疗策略。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

FIP200 Methylation by SETD2 Prevents Trim21-Induced Degradation and Preserves Autophagy Initiation.

DOI：
10.3390/cells11213333
发表时间：
2022-10-22
期刊：
CELLS
影响因子：
6
作者：
Dai, Yuan;Luo, Weijia;Li, Wenjiao;Chen, Zhishi;Wang, Xinjie;Chang, Jiang
通讯作者：
Chang, Jiang

STEMIN and YAP5SA synthetic modified mRNAs regenerate and repair infarcted mouse hearts.

STEMIN 和 YAP5SA 合成修饰的 mRNA 可再生并修复梗塞的小鼠心脏。

DOI：
10.20517/jca.2022.20
发表时间：
2022
期刊：
The journal of cardiovascular aging
影响因子：
0
作者：
Xiao,Siyu;Liang,Rui;Lucero,Emilio;McConnell,BradleyK;Chen,Zhishi;Chang,Jiang;Navran,Stephen;Schwartz,RobertJ;Iyer,Dinakar
通讯作者：
Iyer,Dinakar

Deficient Lmna in fibroblasts: an emerging role of non-cardiomyocytes in DCM.

成纤维细胞 Lmna 缺乏：非心肌细胞在 DCM 中的新兴作用。