# Effect of Mineralocorticoid Receptor Blockade on Coronary Vasculature and Myocardial Structure in HIV

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $699,184

## Abstract

Project Summary: This grant is a competitive renewal of our existing grant (DK-49302) and extends our
investigative focus on the renin-angiotensin-aldosterone system (RAAS) in an independent direction, taking
advantage of novel preliminary data derived from the existing grant demonstrating RAAS activation in HIV
patients. We have shown that RAAS is a key hormone system which relates to critical cardiometabolic indices
in HIV, providing a strong rationale for this proposal, and propose to study detailed endpoints on cardiac
structure and function. Individuals with chronic HIV infection well-treated with antiretroviral therapy (ART)
remain at significant risk for cardiovascular injury and dysfunction, and serious attention should be directed at
the management of CVD risk reduction in HIV. Data provide support for the hypothesis that mineralocorticoid
receptor (MR) activation contributes to inflammation and fibrosis in the heart and vasculature. Consistent with
this hypothesis, our data demonstrate that HIV patients well-phenotyped for metabolic disease have increased
RAAS activation and heightened inflammation under these conditions when compared to non-HIV individuals.
Data also suggest that HIV patients demonstrate an increased prevalence of impaired coronary flow reserve,
myocardial fibrosis, and coronary plaque—all clinically relevant complications of the coronary vasculature and
myocardium associated with cardiovascular mortality. In this regard, no successful treatment strategies exist to
complement ART to reduce CVD risk in HIV. To that end, we propose that treatment with a selective MR
antagonist, eplerenone, for 12 months in a prospective randomized, double-blind, placebo controlled study will
improve indices of the coronary vasculature and the myocardium when compared to placebo in HIV patients.
This is a rational study, as our previous clinical studies have shown an effect of MR blockade on coronary flow
reserve in the diabetes mellitus population, and preclinical evidence supports the effectiveness of MR blockade
on inflammation, fibrosis and atherosclerosis. We will utilize sophisticated radiologic techniques to quantify
baseline risk of coronary flow reserve, myocardial inflammation and fibrosis, and coronary plaque and assess
longitudinal changes in these indices with MR blockade. Information regarding the natural history of these
subtypes of CVD is limited among the HIV population, and thus, these studies will also inform us as to the
progression of disease pathology in the coronary vasculature and myocardium in HIV. Furthermore, we will
evaluate biomarkers of vascular dysfunction, inflammation, and fibrosis to understand the effects of MR
blockade on these indices in relation to radiological assessment of cardiac structure and function. Moreover,
these data will provide critical insight for other non-HIV populations with increased CVD burden. Our
multidisciplinary team will combine expertise in metabolic dysregulation, cardiovascul...

## Key facts

- **NIH application ID:** 10005309
- **Project number:** 5R01DK049302-24
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Gail Kurr Adler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $699,184
- **Award type:** 5
- **Project period:** 1995-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005309

## Citation

> US National Institutes of Health, RePORTER application 10005309, Effect of Mineralocorticoid Receptor Blockade on Coronary Vasculature and Myocardial Structure in HIV (5R01DK049302-24). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10005309. Licensed CC0.

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