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T cells mediate age related arterial dysfunction

T细胞介导年龄相关的动脉功能障碍

基本信息

批准号：
10596594
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
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10596594
关键词：
Acute Adoptive Transfer Aging Aorta Area Arteries Automobile Driving Award Biological Availability Biology Biology of Aging Blood Pressure Blood Vessels CD3 Antigens Cardiovascular Diseases Cardiovascular system Cause of Death Cells Chimera organism Chronic Collaborations Cytoprotection Data Development Plans Diagnostic Doctor of Philosophy Early Diagnosis Elasticity 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 Inflammation Inflammatory Intervention Laboratories Link Measures Mediating Mentors Modeling Mus Nitric Oxide Outcome Outcome Assessment Oxidative Stress 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 infiltration T cell therapy T memory cell T-Cell Depletion T-Lymphocyte Techniques Testing Texas Tissues Training 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 immune cell infiltrate improved in vitro Model innovation insight meetings middle age mortality pharmacologic preservation professor recruit response vascular inflammation

项目摘要

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