# Targeting the Active Resolution of Inflammation for Cardiovascular Disease Prevention

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $742,480

## Abstract

PROJECT SUMMARY
Inflammation is crucial for the host defense response, but unregulated inflammation is a key element of
atherothrombosis and links plaque initiation to subsequent growth and acute rupture, leading to clinical
cardiovascular (CVD) events. Clinical trials of inflammation inhibition have significantly reduced CVD events,
confirmed the inflammation-CVD hypothesis, and stimulated interest in targeting inflammation specifically for
CVD prevention. Such therapies could have widespread impact, since residual inflammatory risk in clinical
practice is common and undertreated. Importantly, recent evidence demonstrates that the resolution of
inflammation is not a passive process but occurs in an active coordinated process involving chemical
mediators called specialized pro-resolving mediators (SPMs) that include resolvins, maresins, lipoxins,
protectins (neuroprotectins), and aspirin-triggered pro-resolving mediators, each with characteristic biological
actions. Yet a major gap in knowledge is which specific SPMs or sets of SPMs may be cardioprotective in
human populations. Motivated by our exciting preliminary findings that plasma levels of certain SPMs are
related to CVD risk and inflammatory traits, and in response to NHLBI NOT-ES-20-018: Promoting
Fundamental and Applied Research in Inflammation Resolution to identify the role of SPMs in CVD, we
propose to test the hypothesis that specific SPMs are early indicators of CVD protection from
inflammation and are associated with its resolution over time. This cost-efficient proposal leverages
resources from three well-phenotyped and genotyped prospective studies. We will examine an extensive panel
of circulating plasma SPMs and proinflammatory mediators using a high-throughput mass spectrometry assay
in relation to incident CVD (total 2339 cases) including repeated measures over time in a subset. Our primary
aims are to: 1) Evaluate associations of SPMs with future CVD events in primary and secondary prevention
populations enriched with chronic inflammation, and assess effect modification by randomized aspirin therapy
vs placebo since aspirin has important pro-resolving effects on SPM biosynthesis; 2) Examine associations of
circulating SPMs with CVD risk factors and downstream biomarkers and cytokines of systemic inflammation;
and perform genome-wide association study of circulating SPMs, to better understand biological pathways for
mechanistic insights into SPM functions; and 3) Assess temporal changes in SPMs over time in relation to
concomitant changes in levels of downstream proinflammatory biomarkers and cytokines, and examine
modulation of SPMs with randomized low-dose methotrexate vs placebo. We will examine functional actions of
the relevant CVD-associated SPMs using ex vivo leukocyte assays for inflammatory gene expression and
macrophage pro-resolving function. Results from this proposal will identify and validate resolution mediators
and pathways that may play a pivotal role in card...

## Key facts

- **NIH application ID:** 10755726
- **Project number:** 5R01HL160799-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** SAMIA MORA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $742,480
- **Award type:** 5
- **Project period:** 2021-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10755726

## Citation

> US National Institutes of Health, RePORTER application 10755726, Targeting the Active Resolution of Inflammation for Cardiovascular Disease Prevention (5R01HL160799-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10755726. Licensed CC0.

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