# Stress and Atherosclerotic Plaque Macrophages - A Systems Biology Approach

> **NIH NIH P01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $2,577,339

## Abstract

SUMMARY
 Chronic social stress is an integral part of our busy contemporary lives. Abundant data show that
severe chronic psychosocial stress is a risk factor for cardiovascular disease and a predictor of myocardial
infarction and stroke. The mechanisms by which stress contributes to the higher cardiovascular event rates are
primarily attributed to secondary effects on behavior, including smoking or food intake. How stress' effect on
the brain can directly impact cardiovascular disease is uncharted territory.
 Preclinical preliminary data from this Program's investigators describe a direct causal link between
social stress, neural signals, and atherosclerosis, the lipid-driven chronic inflammatory disease that is the
underlying cause of myocardial infarction and stroke. The key connecting component is the macrophage, a
large phagocytic leukocyte that originates in the bone marrow and accumulates in atherosclerotic lesions.
Informed by abundant published and unpublished data, we hypothesize that chronic variable stress aggravates
cardiovascular disease by interfering with macrophage dynamics.
 Specifically, we wish to (i) understand how stress biologically affects macrophage dynamics in
atherosclerosis; (ii) develop technology that monitors macrophage dynamics non-invasively; and (iii) elucidate
the mechanism by which post-traumatic stress disorder (PTSD) leads to atherosclerosis. Our highly innovative
Program Project comprises a diverse team of investigators with complementary expertise in cardiovascular
immunology (Swirski, Fisher, Moore); preclinical cardiovascular imaging (Mulder, Nahrendorf, Calcagno);
translational imaging (Fayad, Tawakol, Mani, Fuster); and neuroscience (Murrough, Shin, Pitman, Charney).
Structurally, we have 3 main Projects complemented by an Administrative/Statistical Core and Imaging Core.
 We will tackle the Program Project's central hypothesis in three Specific Aims from the vantage points
of biology, technology, and medicine. In Aim 1 (Biology) we will investigate how stress controls macrophage
dynamics in mouse models of atherosclerosis. In Aim 2 (Technology), we will develop and translate non-
invasive imaging approaches and nanotechnologies that monitor macrophage dynamics in atherosclerosis
during stress. In Aim 3 (Medicine), we will elucidate the mechanism by which PTSD leads to atherosclerosis.
 Our Program Project's overarching and long-term goal is to collectively institute a sound scientific
foundation for the biomedical and clinical community as how the link between stress and cardiovascular
disease can be best approached and integrated in patient care.

## Key facts

- **NIH application ID:** 10116442
- **Project number:** 5P01HL131478-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Zahi A. Fayad
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,577,339
- **Award type:** 5
- **Project period:** 2017-03-17 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116442

## Citation

> US National Institutes of Health, RePORTER application 10116442, Stress and Atherosclerotic Plaque Macrophages - A Systems Biology Approach (5P01HL131478-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116442. Licensed CC0.

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