# Aldosterone and Cardiovascular Disease:  Research and Mentoring Program

> **NIH NIH K24** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $121,469

## Abstract

PROJECT SUMMARY/ABSTRACT
This K24 competitive renewal application is to provide support for protected time for: 1) my mentoring and
teaching of junior clinical investigators; and 2) patient-oriented research investigating the role of aldosterone
and the mineralocorticoid receptor (MR) in the pathophysiology of cardiovascular (CV) disease.
Aldosterone activates the MR and can cause vascular and cardiac inflammation and fibrosis. With support from
the first five years of K24 funding, we showed that, in individuals with well-controlled diabetes, treatment with a
MR antagonist improves coronary flow reserve, a measure of coronary vascular function. In these same
individuals, elevated aldosterone levels were associated with increases in myocardial extracellular volume
(ECV), a measure of cardiac inflammation and fibrosis. These findings suggest that, in diabetes, MR activation
contributes to impaired coronary flow reserve and increased myocardial ECV; both of which predict increased
CV morbidity and mortality in diabetes. In addition, our preliminary data indicates that individuals with
metabolic disturbances, increased visceral adiposity and insulin resistance, and HIV have elevated aldosterone
levels. Individuals with HIV, well-treated with antiretroviral therapy, have impaired coronary flow reserve,
increased myocardial ECV, and increased coronary plaque. They are at increased risk of CV disease as
compared to non-HIV individuals. This increased risk of CV disease cannot be accounted for by traditional CV
risk factors and no successful treatment strategies exist to complement antiretroviral therapy to reduce CVD
risk in HIV. This proposal tests the hypothesis that excess MR activity leads to coronary vascular dysfunction,
myocardial inflammation and fibrosis, and increased coronary plaque in HIV. Thus, we will perform a
randomized, double blind, placebo controlled trial to demonstrate that treatment with a selective MR
antagonist, eplerenone, for 12 months improves coronary flow reserve (Specific Aim 1), myocardial ECV
(Specific Aim 2) and coronary plaque (Specific Aim 3). We will utilize sophisticated radiologic techniques
(cardiac PET, cardiac MRI and coronary CTA) to quantify these CV outcomes.
This research, which is the first comprehensive investigation of MR blockade on CV disease in HIV, aims to
provide novel mechanistic insights and a promising strategy for CVD risk reduction in HIV. Moreover, these
data should provide critical insight for other non-HIV populations with increased CVD burden. These studies
will provide a fertile area for investigation by trainees interested in patient-oriented research and in identifying
new, effective treatments of cardiovascular disease in patients with metabolic disorders.

## Key facts

- **NIH application ID:** 10155549
- **Project number:** 5K24HL103845-10
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Gail Kurr Adler
- **Activity code:** K24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $121,469
- **Award type:** 5
- **Project period:** 2011-05-02 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155549

## Citation

> US National Institutes of Health, RePORTER application 10155549, Aldosterone and Cardiovascular Disease:  Research and Mentoring Program (5K24HL103845-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10155549. Licensed CC0.

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