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

• 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
• 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

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 西方饮食（WD）的过度消费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。长期摄入这类食物会导致心肌病， 收缩功能障碍和代谢紊乱，包括肥胖和糖尿病。同时， 病理性疾病如肥胖、胰岛素抵抗和糖尿病可引起这种有害的 环境在心中。 因此，大多数关于WD心脏紊乱的研究与以下因素密切相关： 糖尿病和肥胖心肌病的研究，由于它们的自然联系和重叠。因为 这种疾病的复杂性，最初的分子信号，触发心脏紊乱， 代谢综合征的研究相对不足，仍然是该领域的一个挑战。 在临床情况下，患者在发生心脏病之前有一个相对的“健康期”（亚临床）， 功能障碍和代谢综合征后，过量消费WD。的签名简介 在亚临床期，心脏中的有害分子信号传导在很大程度上仍然未知， 人类研究的挑战。 高碳水化合物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可以完全模仿 在动物模型中，WD饲料已被很好地表征并广泛用于各种动物研究。 由于长期WD会导致肥胖、糖尿病、心力衰竭甚至合并冠状动脉 对于疾病，研究人员选择短期WD喂养，以探索早期表观遗传信号，而不 这些全球性慢性综合征的共患病。 动物模型包括心脏特异性基因敲除和心脏特异性基因过表达 转基因小鼠。从这一建议的机制研究结果应导致临床意义， 为今后的药物转化和预防提供基础。