Epigenetic signaling, pathological cardiac hypertrophy and Western diet

表观遗传信号、病理性心脏肥大和西方饮食

基本信息

批准号：
10593054
负责人：
Jiang Chang
金额：
$ 54.42万
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：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10593054
关键词：
Animal Model Animals Bioinformatics Biological Assay Biological Markers Carbohydrates Cardiac Cardiomyopathies Chromatin Chronic Clinical Complex Consumption Coronary Arteriosclerosis Data Dependovirus Development Diabetes Mellitus Diet Disease Down-Regulation Early Diagnosis Environment Epigenetic Process Fatty Acids Fatty acid glycerol esters Food Foundations Functional disorder Future Genes Genetic Goals Heart Heart Diseases Heart Hypertrophy Heart Injuries Heart failure Heterozygote High-Throughput Nucleotide Sequencing Histones Human Hyperlipidemia Hypertrophy In Vitro Insulin Resistance Intake Investigation Knock-out Knockout Mice Knowledge Lysine Mediating Metabolic Diseases Metabolic syndrome Methylation Molecular Mus Myocardial dysfunction Obesity Pathologic Patients Pilot Projects Predisposition Prevention Regulation Research Personnel Resources Risk Factors Role SET Domain Series Signal Pathway Signal Transduction Stress Syndrome Testing Tissues Transgenic Mice Translations Transposase Up-Regulation Vascular Diseases Virus Western World Withdrawal clinical development comorbidity diabetic patient experimental study feeding gain of function hemodynamics high throughput screening in vivo insight knock-down loss of function overexpression pharmacologic prevent response sensor sugar therapeutic target tool transcriptome sequencing western diet

项目摘要

PROJECT DESCRIPTION/ABSTRACT Excessive consumption of Western diet (WD) is a risk factor for the development of clinical syndromes such as cardiac dysfunction and obesity. Long-term intake of this type of food can cause cardiomyopathy with contractile dysfunction and metabolic disorders including obesity and diabetes mellitus. Meanwhile, pathological disorders such as obesity, insulin resistance, and diabetes mellitus can elicit this harmful environment in the heart. Therefore, the majority of the studies on cardiac derangement by WD have been closely associated with diabetes and obesity cardiomyopathy investigations due to their natural connection and overlap. Because of this complexity of the disease, the initial molecular signaling that triggers cardiac derangement preceding metabolic syndromes is relatively understudied and remains a challenge in the field. In clinical scenario, patients have a relative “healthy period” (subclinical) prior to the occurrence of cardiac dysfunction and metabolic syndromes after excessive consumption of WD. The signature profiles of deleterious molecular signaling in the heart in this subclinical period remains largely unknown due to obvious challenges in human studies. A high carbohydrate and fatty acid-enriched diet is generally akin to the major cause of obesity in the Western world. While there is no fatty acid-enriched, high carbohydrate diet that could exactly mimic the human diet in animal models, WD feed has been well characterized and widely used in various animal studies. Since long-term WD causes obesity, diabetes mellitus, heart failure and even concomitant coronary artery disease, the investigators chose short-term WD feeding in order to explore early epigenetic signaling without comorbidity of these global chronic syndromes. The animal models include a heart specific knockout as well as a heart specific genetic overexpression transgenic mice. The mechanistic findings from this proposal should result in clinical implications, which provide a foundation for future pharmacological translation and prevention.

项目描述/摘要过度食用西方饮食（WD）是临床综合征发展的危险因素例如心脏功能障碍和肥胖症。这种类型的食物的长期摄入可能会导致心肌病收缩功能障碍和代谢性疾病，包括肥胖和糖尿病。同时，肥胖，胰岛素抵抗和糖尿病等病理疾病会引起这种有害心中的环境。因此，大多数关于WD心脏进化的研究与糖尿病和肥胖心肌病的自然连接和重叠引起的调查。由于这种疾病的复杂性，是触发心脏进化之前的初始分子信号代谢综合征相对理解，并且在该领域仍然是一个挑战。在临床情况下，患者在发生心脏之前具有相对的“健康时期”（亚临床）过量消耗WD后，功能障碍和代谢综合征。的签名概况在这个亚临床时期，心脏中精致的分子信号传导由于明显而在很大程度上尚不清楚人类研究的挑战。高碳水和富含脂肪酸的饮食通常类似于肥胖的主要原因西方世界。虽然没有富含脂肪酸的高碳水化合物饮食，但可以完全模仿在动物模型中的人类饮食中，WD饲料已得到很好的特征，并在各种动物研究中广泛使用。由于长期WD会引起肥胖，糖尿病，心力衰竭甚至伴有冠状动脉疾病，研究人员选择短期WD进食，以探索早期的表观遗传信号传导这些全球慢性综合征的合并症。动物模型包括心脏特异性敲除以及心脏特异性遗传过表达转基因小鼠。该提案的机械发现应导致临床意义，这是为未来的药理学翻译和预防奠定了基础。