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Molecular basis of telomere dysfunction in cardiac dystrophy

心肌营养不良端粒功能障碍的分子基础

基本信息

批准号：
10450879
负责人：
Foteini Mourkioti
金额：
$ 40.11万
依托单位：
UNIVERSITY OF PENNSYLVANIA
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：
2019-08-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10450879
关键词：
Address Adult Affect Age-Months Antioxidants Apoptosis Attenuated Biology Canis familiaris Cardiac Cardiac Myocytes Cardiomyopathies Cardiovascular Diseases Cause of Death Cell Count Cell Size Childhood Chromatin DNA Damage DNA Double Strand Break DNA Repair Pathway Data Defect Development Dilated Cardiomyopathy Duchenne cardiomyopathy Duchenne muscular dystrophy Dystrophin Exhibits Foundations Functional disorder Future Gene Expression Genes Genetic Genetic Transcription Genomic Segment Goals Heart Heart Abnormalities Heart Diseases Heart failure Heterochromatin Human Immunofluorescence Immunologic Inbreeding Investigation Laboratory mice Lamins Length Longevity Mitochondria Molecular Monitor Mus Muscular Dystrophies Mutation Myocardial dysfunction Nuclear Nucleic Acid Regulatory Sequences Organ failure Outcome Oxidative Stress Pathologic Patients Positioning Attribute Proteins Research Respiratory Muscles Role Skeletal Muscle Stains Symptoms Telomere Shortening Telomeric Repeat Binding Protein 2 Testing Therapeutic Therapeutic Intervention Tissues attenuation dystrophic cardiomyopathy experimental study heart function mdx mouse mouse model muscular dystrophy mouse model novel therapeutics p53-binding protein 1 prevent telomere transcriptome sequencing

项目摘要

Project Summary/Abstract Duchenne Muscular Dystrophy (DMD) is the most common childhood form of muscular dystrophy and arises from mutations in the dystrophin gene. DMD is associated with early loss of ambulation and respiratory muscle compromise, followed by the onset of cardiac complications. Although cardiomyopathy is a major cause of death in DMD patients, most therapeutic interventions have focused on skeletal muscle therapies. We recently showed that telomere dysfunction in conjunction with the dystrophin mutation leads to significant structural and functional cardiac defects in mice, with all of the hallmarks seen in DMD patients. The studies proposed here will investigate telomere induced foci in dystrophic cardiomyocytes (Aim 1), identify the role of unknown telomeric mechanisms leading to cardiac failure (Aim 2) and determine the extra-telomeric function of a telomere protein (Aim 3). Understanding the mechanism acting in the progression of cardiac dystrophy will provide new therapeutic possibilities. These studies will also form the foundation for future investigation of similar telomeric mechanisms in other cardiovascular diseases.

项目总结/文摘