# Understanding the role of immune complexes between apolipoprotein A-I and IgG in atherosclerotic cardiovascular disease

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2022 · $376,067

## Abstract

The identification of autoantigens in atherosclerotic plaques has prompted investigation of the antibody-mediated
pathogenesis of atherosclerotic cardiovascular disease (ASCVD). One target of IgG antibody induction in
ASCVD patients is apolipoprotein A-I (ApoA-I), the major protein of high density lipoprotein (HDL). Although anti-
ApoA-I antibodies have been identified in mice and human subjects, their role has not been elucidated. The PI
has identified immune complexes formed between ApoA-I and IgG (ApoA-I/IgG IC) that exhibit anti-inflammatory
characteristics and associate with decreased CVD risk. Continued evaluation of ApoA-I/IgG ICs will improve our
understanding of this component of the immune responses associated with ASCVD. The overall goal of this
project is to determine the role of ApoA-I/IgG ICs and elucidate their functional impact in ASCVD. To achieve
this goal, we will characterize the molecular components of ApoA-I/IgG ICs in mouse and patient sera samples
and correlate these factors with cellular interactions, functional outcomes and disease progression. The
hypothesis is that ApoA-I/IgG ICs exhibit anti-inflammatory effects mediated through the inhibitory Fc-receptor
depending on antibody characteristics (i.e. epitope specificity, subclass), and these effects are capable of
suppressing inflammation and disease. The rationale for this proposed research is that understanding one
component of the humoral immune response associated with ASCVD will lead to a better understanding of the
underlying mechanisms and improve patient outcomes. Encouraged by strong preliminary data, this hypothesis
will be tested through two specific aims: 1) Elucidate the molecular components and functional implications of
ApoA-I/IgG ICs using cultured cells and mouse models of atherosclerosis; and 2) Determine the characteristics
and anti-inflammatory activity of ApoA-I/IgG ICs from human plasma and delineate the association among ApoA-
I/IgG ICs and ASCVD in a large community-based cohort. Aim 1 will employ novel immunomodulation strategies,
developed in Dr. Venditto's laboratory, to achieve epitope-specific immune modulation of antibody responses in
mice to elucidate antibody/epitope function and the role in atherosclerosis progression. Aim 2 will employ sera
from human subjects to characterize antibody/epitope function and evaluate the association between ApoA-I/IgG
ICs and disease progression in the Multi-Ethnic Study of Atherosclerosis (MESA). The approach is innovative
due to the utilization of in vivo immunomodulation approaches to alter ApoA-I/IgG IC profiles, and our approach
focused on obtaining detailed ApoA-I/IgG IC profiles in patients for association studies with disease. The
proposed research is significant as the outcomes of this research will improve our understanding of antibody-
mediated immune responses to ApoA-I to elucidate the role of antibodies on ASCVD progression. Detailed
characterizations of the prefinalantigen, epitope specifici...

## Key facts

- **NIH application ID:** 10431791
- **Project number:** 5R01HL152081-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Vincent Joseph Venditto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $376,067
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10431791

## Citation

> US National Institutes of Health, RePORTER application 10431791, Understanding the role of immune complexes between apolipoprotein A-I and IgG in atherosclerotic cardiovascular disease (5R01HL152081-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10431791. Licensed CC0.

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