# Emerging factors in the pathophysiology of endothelial dysfunction in HIV+ women

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $283,500

## Abstract

Human immunodeficiency virus positive (HIV+) individuals are living longer with antiretroviral
therapy (ART) but are now experiencing coronary artery disease (CAD) as an important cause of death,
especially as they age. Because this CAD is not well explained by conventional CAD risk factors, we
hypothesize that changes that occur in body composition in HIV result in increased metabolically-active
visceral adipose tissue (VAT) in the abdomen and around the coronary arteries (epicardial adipose
tissue: EAT) that releases inflammatory cytokines contributing systemically and locally to the fundamental
processes accelerating CAD in HIV+ individuals. The increased local inflammation resulting from EAT
may contribute to the process of coronary endothelial dysfunction which plays a critical role in the
progression and clinical manifestations of CAD, and is a marker for sub-clinical disease, an independent
predictor of adverse cardiac events, and a potential target for medical interventions. Moreover in HIV+
women other factors may be important in endothelial dysfunction such as a reduced ovarian reserve and
other hormonal abnormalities that commonly affect women with HIV. We recently developed
noninvasive, reproducible MRI-based methods to measure coronary endothelial function (CEF). This new
ability to noninvasively evaluate CEF offers a means to probe mechanisms contributing to CAD
pathophysiology HIV+ women and men. We propose in this application to determine 1) whether CEF
and markers of inflammation and EAT are inversely related in HIV + people, 2) whether this relationship
differs in women compared with men living with HIV and 3) whether reduced ovarian reserve is
associated with endothelial abnormalities in HIV+ women. We will determine in HIV+ people whether
reduced CEF can be explained, at least in part, by increased inflammation. Together these studies will
offer new pathophysiologic insights into HIV-associated vascular disease, and how the pathophysiology
may differ between women and men living with HIV. These studies are critical first steps to better
understanding sex-differences in vascular disease that develops commonly in HIV. The proposed study is
clinically feasible in the proposed time period, and could be used to design future therapeutic intervention
studies, and may offer a fundamentally new understanding of the most important contributing factors of
endothelial dysfunction in HIV.

## Key facts

- **NIH application ID:** 10115108
- **Project number:** 5R01HL147660-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Allison G Hays
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $283,500
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115108

## Citation

> US National Institutes of Health, RePORTER application 10115108, Emerging factors in the pathophysiology of endothelial dysfunction in HIV+ women (5R01HL147660-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10115108. Licensed CC0.

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