# Necroptosis Impairs Inflammation-Resolution Programs in Atherosclerosis

> **NIH NIH R01** · ALBANY MEDICAL COLLEGE · 2020 · $438,018

## Abstract

Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the industrialized world. Studies
over the last decade suggest that failed resolution of a chronic inflammatory response is an important driving
force in the progression of atherosclerosis. Accordingly, two critical unanswered questions are: (a) what are
the endogenous mechanisms underlying dysregulated resolution programs in atherosclerosis and (b) what
mechanism-based treatment strategies can be conceived to initiate resolution when it fails? The resolution of
inflammation is regulated, in part, by specialized pro-resolving mediators (SPM) that comprise omega-6
derived lipoxins and omega-3 derived resolvins, protectins and maresins. The overall objective of this proposal
is to understand the mechanisms of dysregulated resolution in atherosclerosis and to harness SPM signaling
pathways towards a novel treatment strategy. Mechanisms and processes that drive dysregulated resolution
programs in atherosclerosis are of interest. Necroptosis, a specific form of programmed cell death, has recently
emerged as a driver of atherosclerosis progression. Our new work suggests that necroptosis itself impairs
endogenous resolution programs and that key SPMs can limit necroptotic signaling. We proposed a series of
studies to identify the mechanisms associated with necroptosis and impaired resolution (Aim I), the link
between necroptosis and SPM formation in plaques (Aim II) and mechanisms underlying how SPMs evoke
their anti-necroptotic actions on macrophages (Aim III). The link between dysregulated resolution programs
and necroptosis is a completely new and unexplored area of research that may reveal new treatment
strategies for atherosclerosis that are complementary to those that currently exist.

## Key facts

- **NIH application ID:** 9873067
- **Project number:** 5R01HL141127-03
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** Gabrielle Fredman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $438,018
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873067

## Citation

> US National Institutes of Health, RePORTER application 9873067, Necroptosis Impairs Inflammation-Resolution Programs in Atherosclerosis (5R01HL141127-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9873067. Licensed CC0.

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