Epigenomic signaling and heart failure.

表观基因组信号和心力衰竭。

• 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
• 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

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

项目成果

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
• 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。

• DOI: 10.20517/jca.2022.26
• 发表时间: 2022
• 期刊: The journal of cardiovascular aging
• 作者: Wang,Xinjie;Luo,Weijia;Chang,Jiang
• 通讯作者: Chang,Jiang