# Reversing Microvascular Dysfunction in Advancing Age

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2020 · $313,816

## Abstract

Coronary blood flow (BF) reserve (or the ability of the small coronary vessels to increase BF in
response to increased workload) declines in senescent animals and humans and may contribute in the
increased risk for cardiovascular disease (CVD) as a person ages. In addition to this baseline
deterioration of coronary microvascular function, there are some distinct gender-related symptoms of
CVD that have gone untreated. As many as 50% of women referred for evaluation of myocardial
ischemia do not have obstructive coronary disease (like most men) but are frequently associated with
coronary microvascular dysfunction/ischemia. Unfortunately, most traditional therapeutic treatments of
CVD and myocardial ischemia were designed to address symptoms displayed by a majority of men
(with obstructive large coronary vessels), but these methods are not applicable to treating women with
microvascular ischemia. To address the clinical need for an effective microvessel-targeted therapy, we
developed an adipose-derived stromal vascular fraction (SVF) cell therapy and demonstrated that the
cells improved the microvascular coronary blood flow (CBF) and vasoactivity in aged rats. Furthermore,
the therapeutic use of SVF cells improves tissue perfusion independent of vessel density. Building on
this observation, additional findings have determined that the intravenous (i.v.) delivery of autologous,
SVF cells reduced the resting tone of peripheral vasoactive arteries due to the injected SVF cells
spontaneously populating the walls of these arteries in a hydrogen-peroxide-dependent manner.
Therefore, we hypothesize that the i.v. delivery of freshly isolated adipose SVF cells will improve CBF
in aged female rats by populating the walls of small coronary arteries/arterioles promoting vessel
relaxation. To test this, we will use an aged female rat model combined with transgenic reporter-based
cell tracking and functional assessment approaches to determine if coronary microvascular dysfunction
can be reversed through SVF cell injection (Aim 1), to determine the effect of SVF cell incorporation on
vascular network function (Aim 2), and which cell population from the SVF is contributing to the reversal
of coronary microvascular dysfunction (Aim 3). To date, there a lack of cellular therapy designed to
treat dysfunctional coronary microvessels as a result of advanced age, and this particular autologous
cellular therapy has high clinical potential with findings applicable to a broad array of other
microvascular disorders. In addition, we foresee our findings to have broad therapeutic relevance and
provide new insight into the dynamics of vessel wall homeostasis and microvascular disease.

## Key facts

- **NIH application ID:** 9878728
- **Project number:** 5R01AG053585-04
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Amanda Jo LeBlanc
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $313,816
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878728

## Citation

> US National Institutes of Health, RePORTER application 9878728, Reversing Microvascular Dysfunction in Advancing Age (5R01AG053585-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878728. Licensed CC0.

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