# Inflammation-resolution impairments in aging and atherosclerosis

> **NIH NIH R01** · ALBANY MEDICAL COLLEGE · 2024 · $778,674

## Abstract

SUMMARY
Aging is a major risk factor for atherosclerotic cardiovascular disease (CVD) and yet mechanisms as to
how aging impacts this disease remains vastly underexplored. Aging is associated with non-resolving
inflammation (inflammaging). The resolution of inflammation requires the balance between pro-
inflammatory leukotrienes (LTs, e.g. LTB4) or prostaglandins (PGs) and w3-derived specialized pro-
resolving mediators (SPMs), like resolvins. While it is now known that atherosclerosis is associated with
a reduced SPM:LT or PG mediator ratio, major gaps exist in our understanding of (a) the mechanisms
regulating impaired resolution in age-related atherosclerosis and (b) how SPMs promote resolution. Our
objective is to investigate mechanisms of defective resolution in aging so that we can develop novel
strategies to treat atherosclerosis in the physiological context of aging. We found a new links in which
aged atherosclerotic mice had impaired resolution of atherosclerosis, exhibited exuberant granulopoiesis
and defective SPM signaling in the bone marrow. We propose three highly integrated, but independent,
Aims to address mechanisms regulating myelopoiesis in aging and atherosclerosis and to determine the
efficacy and mechanisms of resolvin therapies in aging and atherosclerosis. These Aims will address a
fundamental gap in our understanding of the physiologically relevant context of aging in atherosclerosis.
Completion of the proposed studies will provide mechanistic insight into dysregulated resolution
processes in aging, define cells, mediators and mechanisms restraining plaque resolution/regression in
aging, and establish rationales for new therapies.
.

## Key facts

- **NIH application ID:** 10843246
- **Project number:** 5R01HL170249-02
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** Gabrielle Fredman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $778,674
- **Award type:** 5
- **Project period:** 2023-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843246

## Citation

> US National Institutes of Health, RePORTER application 10843246, Inflammation-resolution impairments in aging and atherosclerosis (5R01HL170249-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10843246. Licensed CC0.

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