# Stress-induced immune reprogramming in cardiovascular disease

> **NIH NIH P01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $2,247,317

## Abstract

PROJECT SUMMARY
 Psychosocial stress is a critical risk factor for cardiovascular disease. However, current
cardiovascular risk management strategies include few evidence-based interventions to address
psychosocial stress’s detrimental effects on this disease. With the current global events, notably the
ongoing COVID-19 pandemic and the increasing burden of atherosclerotic heart disease, modulating
stress’ effects is warranted. The goal of our current proposal is mechanistically understanding psychosocial
stress’s impact on the immune system and inflammatory atherosclerosis to lower residual cardiovascular
risk in patients.
 Over the course of our Type-1 Program, we substantially contributed to knowledge about the links
between psychosocial stress and cardiovascular disease by identifying tissular, cellular, and molecular
pathways that connect nervous, immune, and vascular systems. Specifically, we found that stress
perception mechanisms influence atherosclerosis development and regression. We developed
sophisticated tools to study specific brain regions and their contributions to stress perception. We made
substantial progress on translational imaging studies in atherosclerosis. In clinical studies, we are gaining
ground on understanding the neuro-immune-arterial pathway.
 Our collaborative efforts to studying how stress affects the immune system have yielded new,
innovative research questions we are now eager to explore. Drawing on our Type-1 Program, in the current
proposal, we will not merely investigate macrophage biology; we will broaden our scope to acquire a
complete picture of immune reprogramming in psychosocial stress-aggravated atherosclerotic disease. Our
Program’s broader perspective includes more expansively evaluating different brain circuits and employing
a wide variety of imaging methods while pursuing more in-depth analyses (omics) and optimal data
integration. This innovative approach will elevate our understanding of the complex interrelation between
stress perception and cardiovascular immunology, simultaneously extending the Program’s clinical scope.
 We will approach this highly innovative program with our multidisciplinary team including the
previous program’s principal investigators, most of its key investigators, as well as new collaborators in
neuroscience, psychiatry, and trained immunity. Our program will yield critical insights into how stress-
induced immune reprogramming exacerbates (ongoing) cardiovascular disease. Its successful completion
will not only lay the foundation for unique (i) scientific insights into immune mechanisms that are regulated
neurologically and drive cardiovascular disease development but also yield (ii) a forward-thinking approach
to managing cardiovascular disease in individuals experiencing prolonged episodes of psychosocial stress
and identify novel (iii) therapeutic targets and treatments.

## Key facts

- **NIH application ID:** 10891352
- **Project number:** 5P01HL131478-07
- **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:** 2024
- **Award amount:** $2,247,317
- **Award type:** 5
- **Project period:** 2017-03-17 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891352

## Citation

> US National Institutes of Health, RePORTER application 10891352, Stress-induced immune reprogramming in cardiovascular disease (5P01HL131478-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10891352. Licensed CC0.

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