# Psychosocial stress' effects on macrophage dynamics in atherosclerosis

> **NIH NIH P01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $851,250

## Abstract

SUMMARY
Atherosclerosis, the underlying cause of myocardial infarction and stroke, is a lipid-driven
chronic inflammatory disease characterized by lipoprotein and leukocyte accumulation in the
vessel wall. Among leukocytes, monocyte-derived intimal macrophages are arguably the most
decisive contributors to the development, progression, exacerbation, and regression of
atherosclerosis. As key effectors of inflammation, proteolysis, oxidative stress, lipid clearance,
and efferocytosis, macrophages have long been therapeutic targets for the treatment of
atherosclerosis. However, macrophage content in the vessel wall is highly dynamic, relying on
multiple systemic and local processes that are governed by distinct biological pathways.
Recently, we showed that psychosocial stress, which potentiates cardiovascular disease (CVD),
aggravates atherosclerosis by disturbing the macrophage supply chain; animals subjected to
intermittent psychosocial stress developed inflamed lesions containing more numerous
macrophages than controls. In this project, we will ask how stress affects mechanisms related to
influx of monocytes (medullary myelopoiesis, mobilization of monocytes and stem cells,
extramedullary myelopoiesis, and monocyte influx to lesions), macrophage accrual in lesions
(macrophage differentiation and local proliferation), and macrophage efflux (macrophage death
through apoptosis, necrosis, or secondary necrosis, and macrophage emigration). Collectively,
we refer to these as macrophage dynamics. We will investigate the impact of stress on
macrophage dynamics in the progression and regression of atherosclerosis, with specific focus
on the sympathetic nervous system and neuronal guidance cues. We will identify the decision
nodes that control processes related to macrophage dynamics with the ultimate aim of targeting
them therapeutically.

## Key facts

- **NIH application ID:** 10116447
- **Project number:** 5P01HL131478-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Filip K Swirski
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $851,250
- **Award type:** 5
- **Project period:** 2017-03-17 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116447

## Citation

> US National Institutes of Health, RePORTER application 10116447, Psychosocial stress' effects on macrophage dynamics in atherosclerosis (5P01HL131478-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10116447. Licensed CC0.

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