# Myocardial Vulnerability to Ischemia-Induced Dysfunction and Heart Failure: The Impact of HIV/SIV, ART, and Targeted Immunotherapy

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $799,089

## Abstract

SUMMARY
People with human immunodeficiency virus (HIV) have 1.25- to 2-fold higher risks for myocardial infarction (MI)
and heart failure (HF) than people without HIV. Coronary ischemia and MI are the most common causes of HF
in general and may be particularly important causes of HF for people with HIV (PWH); we recently
demonstrated that PWH with viral control on antiretroviral therapy (ART) have twice the extent of heart muscle
(myocardial) damage after MI than people without HIV who had similar risk factors and coronary anatomy. A
potential reason for these findings relates to persistent immune dysregulation and improperly targeted
inflammation which characterize chronic HIV on ART. These may make PWH especially vulnerable to onset
and propagation of MI during ischemia, as well as myocardial damage and resulting HF during and after MI.
Chronic immune activation and inflammation are associated with heightened cardiovascular risks for PWH, and
these associations are stronger for PWH than uninfected people. However, it is unknown how HIV-related
abnormalities in immune activation affect cardiac damage, dysfunction, and ultimately HF resulting from
coronary ischemia and MI. Observational studies alone cannot answer this question. Informative animal
models are therefore required to (1) determine how HIV, ART, and related immune dysregulation may impact
ischemic cardiac remodeling and resulting HF, and (2) identify immunomodulatory therapies that ameliorate
ischemic cardiac damage, dysfunction, and HF in HIV. In this application, we propose to determine the roles of
HIV/simian immunodeficiency virus (SIV), ART, as well as specific lymphoid cell subsets and chemotactic
factors in post-MI adverse cardiac remodeling. We will use a novel model of ischemia-reperfusion MI that our
co-PIs – one a cardiologist and clinical/translational researcher, one a basic scientist with expertise in
nonhuman primate models of HIV – piloted successfully in SIV+ pigtailed macaques. Our closed-chest MI
model most closely mirrors contemporary human MIs and our SIV+ pigtailed macaque model most closely
reproduces HIV-related immune responses. This will enable us to determine effects of HIV/SIV and ART on
post-MI cardiac structure and function in Aim 1. In Aim 2, we will perform targeted depletions of CD4+ and
CD8+ T cells to determine the role of these subsets in HIV/SIV-related response to MI. Finally, in Aim 3, we will
administer targeted immunotherapies to block T cell activation/co-stimulation and inhibit peripheral monocyte
recruitment and trafficking – immuno-modulatory interventions that may be particularly promising in quelling
SIV/HIV-related immune activation and ameliorating post-MI damage. Our application is highly responsive to
the National Heart, Lung, and Blood Institute (NHLBI)'s notice of special interest (NOSI) NOT-HL-19-677 for
applications proposing exploratory and innovative research to understand HIV-associated cardiovascular
diseases. We expect that o...

## Key facts

- **NIH application ID:** 10082623
- **Project number:** 1R01HL154862-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Matthew Joel Feinstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $799,089
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082623

## Citation

> US National Institutes of Health, RePORTER application 10082623, Myocardial Vulnerability to Ischemia-Induced Dysfunction and Heart Failure: The Impact of HIV/SIV, ART, and Targeted Immunotherapy (1R01HL154862-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10082623. Licensed CC0.

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