# Trained immunity as a link between Inflammatory Arthritis and development of Cardiovascular Disease

> **NIH NIH R03** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $139,895

## Abstract

SUMMARY
Trained immunity describes the relatively new observation that exposure to inflammation alters the
innate immune cells, monocytes and neutrophils, to alter their behavior such that they respond to a
second stimuli with more efficiency. This process is akin to the immunologic memory of the adaptive
immune system. Initially observed in response to pathogens and vaccination, it is now increasingly
clear that sterile, chronic inflammation leads to systemic reprogramming of macrophages. While
developed to improve efficiency of pathogen clearance, this mechanism comes at the cost of promoting
cardiovascular disease. Rheumatoid arthritis (RA), a common, chronic autoimmune disease, carries
the burden of premature mortality to cardiovascular disease. No studies have directly tested whether
inflammatory RA induces trained immune responses in innate cells of the arthritic joint or in the aortic
wall. This proposal hypothesizes that trained immunity occurs in response to RA in the macrophages
of the joint and in the bone marrow. Additionally, we propose that this training of the innate immune
system causes the macrophages of the aorta to become pro-atherogenic, and thus promote
development of atherosclerosis. The overarching hypothesis of this proposal is that trained immunity
is a novel cause behind the increased incidence of cardiovascular disease in RA patients, and proposes
to test this hypothesis using murine models. The PI is a K01 awardee in her 4th year of funding and will
use these pilot studies to pursue her long term research goal to pursue mechanisms linking RA and
cardiovascular disease. Indeed, these studies will provide the pilot data necessary to pursue
independent R01 funding exploring the links between inflammatory arthritis, trained immunity, and
cardiovascular disease.

## Key facts

- **NIH application ID:** 10870309
- **Project number:** 1R03AR084000-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Susan C. MacLauchlan
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $139,895
- **Award type:** 1
- **Project period:** 2024-09-19 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870309

## Citation

> US National Institutes of Health, RePORTER application 10870309, Trained immunity as a link between Inflammatory Arthritis and development of Cardiovascular Disease (1R03AR084000-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10870309. Licensed CC0.

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