# Macrophage Trafficking, Inflammation & Metabolism in Atherosclerosis Regression in Diabetes

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $533,864

## Abstract

Project 1: Summary
The relationship between diabetes and atherosclerosis is well established. Indeed, people with diabetes are
overwhelmingly likely to suffer from coronary heart disease (CHD). Though the relative risk of CHD falls with
statin treatment of diabetics, the absolute risk remains elevated compared to non-diabetics, consistent with our
finding in animal models that diabetes impairs plaque regression after lipid lowering. In Project 1, we propose
to use these models to determine how diabetes maintains in atherosclerotic plaques high levels of
macrophages and their inflammatory state despite aggressive reductions in hyperlipidemia. A major goal is to
determine the kinetic bases for the increased content of plaque macrophages in diabetic atherosclerotic mice
after lipid reduction. The possibilities include changes in the recruitment of monocytes to the plaques, the
retention or chemostasis of plaque macrophages, the degree of macrophage apoptosis or efferocytosis, and
the proliferation of macrophages in the plaques. We will extend our initial studies in mice with type 1 diabetes
(T1D) to mice with diet-induced obesity (DIO) and insulin-resistance (IR) as a model of the IR, high-CHD risk
states (metabolic syndrome, type 2 diabetes), prevalent in the US population. We will also test the roles of
candidate factors in the maladaptive macrophage responses to diabetes despite lipid lowering. These include
netrin-1, a macrophage retention molecule (also to be studied in adipose tissue under Project 2), RAGE, the
receptor for advanced glycation endproducts (which we find also promotes macrophage retention), and
ACSL1, an inflammatory factor induced by hyperglycemia. For the first 2, we will explore their translational
potential. We will also employ unbiased, genome-based, bioinformatic approaches to uncover new
factors/pathways that regulate macrophage content and inflammation not only in plaques, but in combination
with Projects 2 and 3, also in adipose tissue in DIO mice.

## Key facts

- **NIH application ID:** 10150066
- **Project number:** 5P01HL131481-05
- **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:** 2021
- **Award amount:** $533,864
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150066

## Citation

> US National Institutes of Health, RePORTER application 10150066, Macrophage Trafficking, Inflammation & Metabolism in Atherosclerosis Regression in Diabetes (5P01HL131481-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10150066. Licensed CC0.

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