# Impact of T cells on age-related vascular dysfunction: A translational approach

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $421,689

## Abstract

Project Summary/Abstract
Cardiovascular disease (CVD) is the leading cause of death in the United States and aging is an independent
risk factor for CVD. With the expansion of the aging population, by 2030 >40% of the population is projected to
have CVD. Advanced age is accompanied by blunted endothelium-dependent dilation (EDD), reductions in
nitric oxide (NO) bioavailability and increased large artery stiffness, important contributors to CVD risk. Arterial
inflammation plays an important role in these processes but the precise link is unclear. We will utilize a
translational approach to determine whether T cells play a role in age-related chronic arterial inflammation and
subsequent dysfunction. First, we hypothesize that with aging, pro-inflammatory T cells accumulate around
arteries and exacerbate 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, depleted or inhibited. In
addition, we will employ adoptive transfer to determine whether age-related arterial dysfunction results from
intrinsic age-related changes to T cells, increased T cell recruitment to the aged artery, or both. Second, we
hypothesize that T cells from older human donors will home to the vasculature of humanized immuno-deficient
mice and induce inflammation and subsequent arterial dysfunction. To test this hypothesis, we will adoptively
transfer T cells from young and older healthy human donors to young and old NOD-scid/γcnull/A2 humanized
mice and assess immune cell infiltration, inflammation, arterial function, and ROS. Third, we hypothesize that
inhibition of T cell activation will improve arterial function in older adults. To test this hypothesis, we will assess
vascular function and endothelial cell and T cell inflammatory phenotype in older humans before and after
treatment with placebo or a T cell inhibitor, Abatacept. The results of 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.

## Key facts

- **NIH application ID:** 9912683
- **Project number:** 5R01AG060395-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Anthony John Donato
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $421,689
- **Award type:** 5
- **Project period:** 2019-04-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912683

## Citation

> US National Institutes of Health, RePORTER application 9912683, Impact of T cells on age-related vascular dysfunction: A translational approach (5R01AG060395-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9912683. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*