# Preclinical imaging of immune responses to chronic stress

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $626,740

## Abstract

SUMMARY
 Psychosocial stress contributes to cardiovascular disease at several stages, including promoting
coronary artery disease progression and acutely triggering cardiac events1,2. In this project, we aim to investigate
both acute and chronic stress exposure and their immediate and long-term effects on the immune system and
atherosclerosis. We will approach these important questions through the development and application of non-
invasive imaging methods.
 Stress activates diverse signaling circuits in the brain, including the hypothalamic-pituitary-adrenal (HPA)
axis and the sympathetic nervous system (SNS), which subsequently affect leukocyte distribution and function
as well as atherosclerotic plaque inflammation. Specifically, HPA axis activation during acute stress controls
lymphocyte and monocyte homing to the bone marrow, while neutrophils are rapidly mobilized from the bone
marrow due to motor cortex signaling3. In parallel, SNS activation leads to the production of catecholamines,
which induce a long-lasting pro-inflammatory phenotype in monocytes based on metabolic and epigenetic
rewiring4,5. SNS activation due to stress has also been directly linked to enhanced atherosclerotic plaque
inflammation6,7. During chronic stress exposure, direct sympathetic signaling enhances the proliferation of
hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (hematopoiesis), leading to higher
numbers of circulating pro-inflammatory neutrophils and monocytes6,8. These cells subsequently extravasate
into the arterial wall and enhance plaque inflammation.
 We hypothesize that stress exposure induces long-term effects on the immune system through the
induction of trained immunity and changes in myeloid cell dynamics. In this highly innovative project, we will
employ newly developed and established PET imaging methods to probe stress’s effects on the immune
system and atherosclerotic plaque inflammation longitudinally, in vivo, and at a whole-body level. In Aim 1, we
will focus on metabolic and epigenetic rewiring in hematopoietic organs over the course of stress exposure and
after stress withdrawal. Aim 2 evolves around stress-induced alterations in myeloid cell dynamics (cell
proliferation, migration, egress, and myeloid cell burden), probed by sophisticated imaging methods.
 Completing these Aims will help decipher stress’s immediate and long-term impact on the immune
system though unique integration of molecular biology and immunology with state-of-the-art translational
cardiovascular imaging research.

## Key facts

- **NIH application ID:** 10878890
- **Project number:** 5R01HL169500-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Mandy Maria Theresia van Leent
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $626,740
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878890

## Citation

> US National Institutes of Health, RePORTER application 10878890, Preclinical imaging of immune responses to chronic stress (5R01HL169500-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10878890. Licensed CC0.

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