# Targeting early instigators of vascular inflammation to prevent and/or delay vascular aging in chronic treated HIV

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $335,400

## Abstract

PROJECT SUMMARY/ABSTRACT
Increased comorbidities associated with aging such as atherosclerotic cardiovascular disease (CVD) is an
emerging problem in HIV-1 infection despite potent antiretroviral therapy (ART). Current therapies (such as
statins) to treat HIV-1-related inflammation, immune activation and CVD are inadequate. Oxidative stress has a
major role in HIV-1 pathogenesis and CVD but it is unlikely that antioxidants alone will be adequate therapy.
Potent antioxidants that also have specific anti-inflammatory effects against pleotropic inflammatory mediators
called oxidized lipids (OxPLs) may be novel therapies to improve HIV-1 related inflammation, immune
activation and CVD. Unraveling how oxidized lipids affect CVD and HIV-1 pathogenesis, may contribute to
development of new therapies to manage HIV-related CVD. High-density lipoproteins (HDLs) are the most
powerful independent negative predictor of CVD evident in all large epidemiological studies. Apolipoprotein A-I
(apoA-I), the major protein of HDL, is responsible for the much of the anti-atherogenic and anti-inflammatory
properties of HDL. These effects can be mimicked by apoA-I peptides such as 4F that are promising therapy
for CVD. Statins and ApoA-I have similar anti-inflammatory properties. Limited evidence from animal studies
has shown that there was enhancement of the biological properties of apoA-I peptides when given with a
statin. Synergy between apoA-I mimetics and statins may in part be at the level of the intestine which may be
an important modulator of atherosclerosis. Monocytes/macrophages (M/M) are at the intersection between
HIV-1 immunopathogenesis, gut biology, atherosclerosis. Given the complex pathogenesis of HIV-1 related
CVD, it is impossible to study exact mechanisms of synergistic effects between statins and apoA-I mimetics in
humans (in vivo). Established patient cohorts within UCLA and primary human cells and lipoproteins can be
used as tools to study ex vivo/in vitro synergistic effects of statin and apoA-I mimetics. In this proposal using an
established physiologically meaningful ex vivo model of atherosclerosis we will explore synergistic effects of
statins and ApoA-I mimetics on mechanisms that determine how oxidized lipoproteins present in chronic
treated HIV-1 infection directly contribute to M/M derived foam cell formation and M/M chemotaxis (Aim 1),
M/M dysfunction (Aims 2) and endothelial activation (Aim 3). We will also expand our findings in vivo (Aim 3) in
middle aged/older (50-70 years old) HIV+ persons on potent ART and subclinical atherosclerosis. In this group,
we will explore whether compared to matched by age, ART group not on statins, participants on statins have
lower plasma levels of oxidized lipoproteins and established surrogate biomarkers and molecular signatures of
M/M and endothelial activation that are known to predict and/or lead to CVD. Such an approach could reduce
the excess morbidity and mortality remaining despite ART in HIV-1 ...

## Key facts

- **NIH application ID:** 9980751
- **Project number:** 5R01AG059502-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Theodoros Kelesidis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $335,400
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980751

## Citation

> US National Institutes of Health, RePORTER application 9980751, Targeting early instigators of vascular inflammation to prevent and/or delay vascular aging in chronic treated HIV (5R01AG059502-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9980751. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*