DHA Mechanisms in Obesity-mediated Cardiac Remodeling Post-Myocardial Infarction

DHA 在肥胖介导的心肌梗死后心脏重塑中的机制

• 批准号: 8309090
• 负责人: Ganesh V Halade
• 金额: $ 9.72万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8309090
• 关键词: Advisory Committees; Affect; Age-Months; Aging; Alternative Medicine; American; Anti-Inflammatory Agents; Anti-inflammatory; Antiatherogenic; Attenuated; Back; Biochemistry; Biology; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cellular biology; Chronic; Complication; Corn Oil; Diabetes Mellitus; Diagnosis; Diet; Discipline; Docosahexaenoic Acids; Echocardiography; Eicosapentaenoic Acid; Epidemic; Etanercept; Extracellular Matrix; Fatty Acids; Fatty acid glycerol esters; Fibroblasts; Fish Oils; Gene Expression; Gene Proteins; Goals; Health; Health Sciences; Histology; Human; Hyperglycemia; Immunoblotting; Individual; Inflammation; Inflammatory; Insulin Resistance; Journals; Left Ventricular Remodeling; Life; Link; Lupus; Macrophage Activation; Mass Spectrum Analysis; Measures; Mediating; Mentors; Modeling; Molecular; Mus; Myocardial Infarction; National Center for Complementary and Alternative Medicine; Nutritional; Obese Mice; Obesity; Omega-3 Fatty Acids; Pathway interactions; Pattern; Phase; Physiological; Physiology; Principal Investigator; Process; Property; Protein Secretion; Proteomics; Research; Research Personnel; Research Training; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Role; Signal Pathway; Signal Transduction; Structure; Supplementation; TNF gene; Testing; Texas; Time; Training; Universities; Ventricular; career; career development; clinically relevant; dietary supplements; experience; feeding; improved; innovation; interest; macrophage; middle age; mouse model; response

DESCRIPTION (provided by applicant): This K99/R00 training application will provide training and research time for Dr. Halade's transition to independence as an NCCAM-focused investigator. The training goal of this project is to obtain additional experience in cardiac biology to allow Dr. Halade to transition to an independent career focused on using nutritional and alternative medicine approaches to improve cardiovascular health. The training plan will be carried out at the University of Texas Health Science Center at San Antonio, and includes individual and team mentoring strategies, additional coursework in cardiac physiology, and presentations at seminars and journal clubs. The principal investigator is strongly supported by his mentor and career development advisory committee that is composed of leading experts in their respective fields. The research goal of this project is to study the anti-inflammatory effect of docosahexaenoic acid (DHA) on TNF-1 signaling following myocardial infarction (MI). I will use a unique model of aging mice that have been fed an n-6 fatty acids (corn oil) diet for six months, beginning at middle-age, to induce obesity. DHA effects will be compared to a TNF-1 antagonist (etanercept). I will test the central hypothesis that DHA attenuates cardiac remodeling following MI by blunting TNF-1-mediated inflammation and extracellular matrix turnover. To test our hypotheses I will: 1) test whether DHA attenuates cardiac remodeling following MI by blunting TNF-1-mediated inflammation and extracellular matrix turnover 2) determine whether DHA attenuates fibroblast activation induced by MI 3) determine whether DHA attenuates macrophage activation induced by MI. My translational and clinically relevant hypothesis has applicability to the far-reaching epidemic of obesity, in which cardiovascular disease is a primary complication amenable to nutritional supplementation. I will use a multi-discipline approach that integrates physiology, cell biology, biochemistry, mass spectrometry, and histological approaches to unveil mechanisms on how aging and obesity influence the LV remodeling process as a function of fibroblast and macrophage activation status. The innovation of this application is that I will use: 1) components of fish oil in order to assign individual constituent functions; 2) mice that are fed high n- 6 fatty acids diet beginning at middle-age, which more closely mimics what is seen in humans; and 3) state of the art approaches that will allow me to develop as an independent investigator. The results of these studies will clarify the role of DHA in post-MI remodeling in the setting of aging and obesity.

描述（由申请人提供）：本K99/R00培训申请将为Halade博士作为以NCCAM为重点的研究者的过渡为独立性提供培训和研究时间。 该项目的培训目标是获得心脏生物学的额外经验，以使Halade博士过渡到专注于使用营养和替代医学方法来改善心血管健康的独立职业。培训计划将在得克萨斯大学圣安东尼奥大学健康科学中心进行，包括个人和团队指导策略，心脏生理学的其他课程以及在研讨会和期刊俱乐部的演讲。他的导师和职业发展咨询委员会的主要研究人员得到了主要研究人员的支持，该委员会由各自领域的领先专家组成。 该项目的研究目的是研究二十六六烯酸（DHA）对心肌梗塞（MI）后TNF-1信号传导的抗炎作用。我将使用一种独特的衰老小鼠模型，该模型已喂入N-6脂肪酸（玉米油）饮食六个月，从中年开始，以诱导肥胖。 DHA效应将与TNF-1拮抗剂（Etanercept）进行比较。我将测试中心假设，即DHA通过钝化TNF-1介导的炎症和细胞外基质转换后会减轻心脏重塑。为了检验我们的假设，我将：1）测试DHA在MI后通过钝化TNF-1介导的炎症和细胞外矩阵周转后是否会减轻心脏重塑。 我的翻译和临床相关假设适用于肥胖的深远流行，其中心血管疾病是补充营养的主要并发症。我将使用一种多学科方法，该方法将生理学，细胞生物学，生物化学，质谱和组织学方法整合起来，以揭示衰老和肥胖如何影响LV重塑过程的机制，这是成纤维细胞和巨噬细胞激活状态的功能。该应用程序的创新是我将使用：1）鱼油的组成部分，以分配单个组成功能； 2）从中年开始喂养高N-6脂肪酸饮食的小鼠，它们更紧密地模仿了人类所见； 3）艺术方法将使我成为独立研究者。这些研究的结果将阐明DHA在MI后重塑在衰老和肥胖环境中的作用。