# Determinants of Regulatory Macrophage Function in Coronary Artery Disease

> **NIH NIH R03** · UNIVERSITY OF CHICAGO · 2021 · $81,000

## Abstract

Project Summary / Abstract
Inflammation is a major contributor to coronary artery disease (CAD), the process that involves build-up of
plaques within the coronary arteries. These plaques result in heart attacks and chronic heart disease due to
poor blood supply to the heart muscle, and thus they explain more worldwide morbidity and mortality than any
other pathological process.
Macrophages are cells of the immune system that are central components of these plaques in CAD. We have
discovered critical factors that determine whether macrophages become inflammatory, associated with worse
disease, or regulatory, which can reduce disease, and will define whether or not one of these central factors,
Skap2, governs the switch from the inflammatory to the regulatory state in plaques. With a clear understanding
of what determines macrophage behavior in the plaque, we aspire ultimately to point to new therapies that
make macrophages more regulatory—stopping them from driving inflammation—and instead inducing them to
heal or stabilize plaques in order to reduce the burden of CAD.
This project is innovative and impactful in several ways. First, as opposed to much prior work done on
macrophage cell lines or cells derived in vitro, it will define the role of key macrophage molecules in this switch
from inflammatory to regulatory function in macrophages isolated directly from the plaque. Second, because
translating finding to humans is paramount, it will measure the same regulatory functions and roles of these
molecules in human macrophages derived from circulating precursor cells obtained from subjects with varying
degrees of CAD, and correlate these findings with plaque composition in humans. Finally, one of the key
regulatory functions the project will assess is “efferocytosis”, the clearing of inflammatory debris by
macrophages, a process recognized as a potential key determinant of halting inflammation in the plaque and a
new treatment target for the future.

## Key facts

- **NIH application ID:** 10223437
- **Project number:** 5R03HL154292-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Francis Joseph Alenghat
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $81,000
- **Award type:** 5
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223437

## Citation

> US National Institutes of Health, RePORTER application 10223437, Determinants of Regulatory Macrophage Function in Coronary Artery Disease (5R03HL154292-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10223437. Licensed CC0.

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