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: 10374047
• 负责人: Jiang Chang
• 金额: $ 53.96万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374047
• 关键词: ATAC-seq; 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; High-Throughput Nucleotide Sequencing; Histones; Human; Hyperlipidemia; Hypertrophy; In Vitro; Insulin Resistance; Intake; Investigation; Knock-out; Knockout Mice; Knowledge; Lysine; Mediating; Metabolic; Metabolic Diseases; Metabolic syndrome; Molecular; Mus; Myocardial dysfunction; Obesity; Pathologic; Patients; Pharmacology; Pilot Projects; Prevention; Regulation; Research Personnel; 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; data resource; diabetic patient; experimental study; feeding; gain of function; hemodynamics; high throughput screening; in vivo; insight; knock-down; loss of function; overexpression; 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 过度食用西方饮食（WD）是发生临床综合征的危险因素 例如心脏功能障碍和肥胖。长期食用此类食物会引起心肌病 收缩功能障碍和代谢紊乱，包括肥胖和糖尿病。同时， 肥胖、胰岛素抵抗和糖尿病等病理性疾病可能会引起这种有害的 心里的环境。 因此，大多数关于 WD 引起的心脏紊乱的研究都与 糖尿病和肥胖症心肌病的研究由于它们的天然联系和重叠而受到关注。由于 这种疾病的复杂性，触发心脏紊乱的最初分子信号传导 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”（亚临床期）。 过量食用 WD 后的功能障碍和代谢综合征。的签名配置文件 由于明显的原因，在这个亚临床时期心脏中有害的分子信号传导仍然很大程度上未知。 人类研究中的挑战。 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、高碳水化合物的饮食可以完全模仿 在动物模型中的人类饮食中，WD 饲料已得到很好的表征并广泛应用于各种动物研究中。 由于长期WD会导致肥胖、糖尿病、心力衰竭，甚至伴随冠状动脉病变 疾病中，研究人员选择短期 WD 喂养，以探索早期表观遗传信号，而无需 这些全球慢性综合症的共病。 动物模型包括心脏特异性基因敲除以及心脏特异性基因过度表达 转基因小鼠。该提案的机制发现应产生临床意义， 为未来的药理学转化和预防奠定基础。