# Macrophage Dysfunction in Atherosclerosis and Cardiometabolic Diseases

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $2,516,567

## Abstract

Summary: Overall
This Program Project grant has unveiled key roles for macrophage metabolism, depot- and cue-dependent
molecular re-programming and intraorgan communications in cardiometabolic dysfunction. The Program Project
team will build upon these discoveries and forge new directions. Macrophages mediate intraorgan
communications and, through interorgan communications, macrophages and other bioactive mediators home to
and infiltrate distinct sites, such as in the atherosclerotic plaque; in obese adipose tissue; and to be newly
explored in this Cycle; in the liver. In cardiometabolic dysfunction, the liver is the recipient of increased endotoxin
from the gut; accumulation of lipid from adipose tissue; and increased bioavailability of damage-associated
molecular patterns. In each metabolic organ, the tissue-specific niche defines the myriad consequences, such
as excess synthesis/deposition of pathological lipids; and recruitment of infiltrating bone marrow-derived immune
cells. These delivered stimuli modulate endogenous signaling pathways in resident adipose tissue macrophages
and liver Kupffer cells and impart immunometabolic imprints on macrophage subsets in atherosclerosis, obesity
and non-alcoholic steatohepatitis (NASH). These concepts are clinically-significant, as atherosclerosis, obesity
and NASH are established risk factors for cardiovascular diseases. The Program Project will explore three
specific aims: First, Aim 1 (Project 1) will determine the mechanisms by which caloric restriction mediates
macrophage intra- and interorgan communications in atherosclerosis, obesity and NASH, and define the impact
of LXRα phosphorylation in liver immune cells on NASH-related factors under study in each Project. Second,
Aim 2 (Project 2) will probe the mechanisms by which netrin-1 and its receptor network mediate macrophage
intra- and interorgan communications in atherosclerosis, obesity and NASH. Third, Aim 3 (Project 3) will probe
the mechanisms by which RAGE/DIAPH1 mediates macrophage intra- and interorgan communications in
atherosclerosis, obesity and NASH. The Program Project will be supported by three cores: Core A
(Administrative, which includes Biostatistics and Bioinformatics); Core B (Pathology and Biochemistry); and Core
C (Mouse Breeding and Procedure Core). Collectively, this highly-motivated Program Project team continues to
work together synergistically to interrogate novel mechanisms by which macrophage intraorgan and interorgan
communications contribute to the mediation and remediation of cardiometabolic disease. Through the
employment of state-of-the-art approaches and shared complementary examinations in human tissues and
human transcriptome databases, this Program Project will discover new mechanistic insights that lead to
therapeutic approaches to quench the exaggerated macrophage accumulation, inflammation and
intra/interorgan communications that amplify cardiovascular risk.

## Key facts

- **NIH application ID:** 10839484
- **Project number:** 5P01HL131481-08
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Edward A Fisher
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,516,567
- **Award type:** 5
- **Project period:** 2017-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839484

## Citation

> US National Institutes of Health, RePORTER application 10839484, Macrophage Dysfunction in Atherosclerosis and Cardiometabolic Diseases (5P01HL131481-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10839484. Licensed CC0.

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