T cells mediate age related arterial dysfunction

T细胞介导年龄相关的动脉功能障碍

• 批准号: 10395462
• 负责人: Daniel Trott
• 金额: $ 12.69万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10395462
• 关键词: Acute; Adoptive Transfer; Aging; Aorta; Area; Arteries; Automobile Driving; Biological Availability; Biology; Biology of Aging; Blood Pressure; Blood Vessels; CD3 Antigens; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cells; Chimera organism; Chronic; Collaborations; Data; Development Plans; Diagnostic; Doctor of Philosophy; Early Diagnosis; Elderly; Endothelial Cells; Endothelium; Environment; Etiology; Extramural Activities; Free Radicals; Functional disorder; Funding; Genetic Models; Goals; Health; Home; Homing; Human; Hypertension; Immune; Immune system; Immunology; In Vitro; Infiltration; Inflammation; Inflammatory; Intervention; K-Series Research Career Programs; Laboratories; Link; Measures; Mediating; Mentors; Modeling; Mus; Nitric Oxide; Outcome; Oxidative Stress; Pharmacology; Pharmacotherapy; Phenotype; Physiologic pulse; Plasma; Play; Population; Pre-Clinical Model; Reactive Oxygen Species; Research; Research Project Grants; Resistance; Resources; Rodent Model; Role; Series; T cell therapy; T memory cell; T-Cell Depletion; T-Lymphocyte; Techniques; Testing; Texas; Tissues; Training; Tumor-infiltrating immune cells; United States; Universities; Vascular Diseases; age related; aged; aging population; arterial stiffness; burden of illness; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; career development; cytokine; endothelial dysfunction; experimental study; humanized mouse; improved; in vitro Model; innovation; insight; meetings; middle age; mortality; preservation; professor; recruit; response; translational study; vascular inflammation

PROJECT SUMMARY Candidate: Daniel Trott, Ph.D. is an Assistant Professor at the University of Texas at Arlington. Dr. Trott's research is focused on the interaction between inflammation and age-related arterial dysfunction. Dr. Trott's long-term goal is to independently direct an extramurally funded laboratory with research focused on the interaction of the aging immune system and vasculature in both pre-clinical models and in humans. Career Development: This award will support Dr. Trott's career development by building on his existing training in aging and vascular biology. Specifically, Dr. Trott will receive extensive training in the planning and execution of studies assessing vascular and immune outcomes in older adults. The career development plan outlines a coordinated effort to train the candidate in areas including: vascular biology of aging, assessment of vascular function in humans, human endothelial cell and immune cell phenotyping, and, attendance at regular aging and vascular seminar series as well as other meetings within the university and nationally. Environment: The University of Texas at Arlington is an ideal environment for Dr. Trott's career development. This environment provides all of the resources needed to complete the proposed studies. Further, his mentoring team allows for collaboration with experts in aging, vascular biology, and immunology. The University of Texas at Arlington also provides a rich environment for formal and informal training in career development. Research: The central hypothesis of this research project is that T cells mediate age-related arterial dysfunction. First, we hypothesize that T cells infiltrate the perivascular tissue around large elastic and resistance arteries and mediate age-related arterial dysfunction. To test this, we will assess arterial function, immune cell infiltration and inflammatory subtypes in young and old mice with T cells intact or depleted. In addition, we will employ adoptive transfer to determine whether aged T cells preferentially home to the vasculature and induce dysfunction. Second, we hypothesize that T cells directly mediate age-related arterial dysfunction in older adults. To test this hypothesis we will adoptively transfer T cells from young, middle aged and older healthy human donors to NOD-scid/γcnull/A2 humanized mice and assess immune cell infiltration, inflammation and arterial function. We will also assess arterial function, plasma free radicals and endothelial and T cell phenotype in the human donors to determine the relationship between these parameters and the degree of dysfunction induced in the recipient mice. The results from these studies will provide insight into the etiology of age-related arterial dysfunction and identify previously unexplored targets for diagnostics and intervention with the significant goal of maintaining cardiovascular health in the elderly.

项目总结 候选人：丹尼尔·特罗特，博士，德克萨斯大学阿灵顿分校助理教授。特罗特医生的 研究的重点是炎症和年龄相关性动脉功能障碍之间的相互作用。特罗特医生的 长期目标是独立指导一个由外部资助的实验室，专注于 在临床前模型和人类中老化的免疫系统和血管系统的相互作用。 职业发展：该奖项将在特罗特博士现有的基础上，支持他的职业发展 衰老和血管生物学方面的培训。具体地说，特罗特博士将接受广泛的规划和培训 执行评估老年人血管和免疫结果的研究。职业发展计划 概述了在以下领域对候选人进行培训的协调努力：衰老的血管生物学，评估 人类的血管功能，人类内皮细胞和免疫细胞的表型，以及定期出席 老龄化和血管系列研讨会以及大学和全国范围内的其他会议。 环境：德克萨斯大学阿灵顿分校是特罗特博士职业发展的理想环境。 这种环境提供了完成拟议研究所需的所有资源。此外，他的 指导团队允许与衰老、血管生物学和免疫学方面的专家进行合作。这个 德克萨斯大学阿灵顿分校也为正式和非正式的职业培训提供了丰富的环境 发展。 研究：该研究项目的中心假设是T细胞调节与年龄相关的动脉 功能障碍。首先，我们假设T细胞渗透到大的弹性血管周围的血管周围组织。 阻力动脉和调节与年龄相关的动脉功能障碍。为了测试这一点，我们将评估动脉功能， T细胞完整或耗尽的幼鼠和老年鼠的免疫细胞浸润和炎症亚型。在……里面 此外，我们将采用收养转移来确定老化的T细胞是否优先回到 血管系统，并导致功能障碍。其次，我们假设T细胞直接介导与年龄相关的动脉 老年人的功能障碍。为了验证这一假设，我们将过继地将年轻人和中年人的T细胞 以及较年长的健康人类捐赠者对NOD-SCID/γCnul/A2人源化小鼠的研究，并评估免疫细胞的渗透情况， 炎症和动脉功能。我们还将评估动脉功能、血浆自由基和内皮细胞 和T细胞表型来确定这些参数和T细胞表型之间的关系 在受体小鼠中诱导的功能障碍程度。这些研究的结果将为我们提供对 年龄相关性动脉功能障碍的病因，并确定以前未探索的诊断和 以维护老年人心血管健康为重要目标的干预。