# Reducing Inflammation for the Prevention of CVD: A Focus on Eicosanoid Pathways

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $710,610

## Abstract

Project Summary/Abstract
 It is now well-recognized that cardiovascular disease (CVD) has many features of a systemic
inflammatory process, and recent studies suggest that CVD can be viewed as a state of defective resolution of
inflammation. Eicosanoids are diet-derived bioactive lipid metabolites of polyunsaturated fatty acids (PUFAs,
e.g. omega-3 and omega-6 fatty acids), and have been implicated as upstream drivers of inflammatory
conditions including CVD. Eicosanoids can both promote inflammation (pro-inflammatory eicosanoids) or
reverse it (anti-inflammatory eicosanoids). The balance of these pro- and anti-inflammatory eicosanoids is
critical for the clinical manifestation of inflammation, and therefore are tightly regulated via cellular signaling
pathways. A major gap in our knowledge is how specific eicosanoid mediators drive the CVD-associated
inflammation in humans, and conversely, how other eicosanoids promote its resolution. Recent advances in
high performance mass spectrometry technology now allow the accurate identification and quantification of
more than 150 distinct eicosanoids and related PUFA species circulating in human plasma. The proposed
study will evaluate a comprehensive panel of pro- and anti-inflammatory eicosanoids in relation to
cardiovascular risk factors and clinical events, as well as assess how diet, drugs, and genetic variants
modulate the delicate balance of eicosanoids. This will be conducted within two large-scale prospective clinical
trials, the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin
(JUPITER) and the VITamin D and OmegA-3 TriaL (VITAL). We will leverage banked blood specimens and
collected clinical trial data from 3,550 men and women (1,275 incident CVD events) to examine eicosanoids in
relation to CVD risk factors and events. In Aim1 we will focus on the JUPITER trial of participants recruited
based on the presence of chronic systemic inflammation to examine the associations (cross-sectional and
change over time) of pro-and anti-inflammatory eicosanoids with CVD risk factors and events, and assess
changes in eicosanoid levels with high-intensity statin therapy versus placebo. In Aim 2, we will replicate the
JUPITER analyses in the VITAL trial, an independent population of older healthy individuals (20% African
Americans). In VITAL, we will assess eicosanoid associations with CVD risk factors and incident events, and
effects of marine omega-3 fatty acid supplementation versus placebo, then we will perform meta-analysis of
the JUPITER and VITAL studies. We will also assess whether the benefits of the interventions differ based on
levels of eicosanoids, and how they are modulated by genetic variants in enzymes involved in eicosanoid
pathways. This comprehensive approach may elucidate specific pro- and anti-inflammatory PUFA derived
eicosanoids associated with CVD, and could trigger therapeutic anti-inflammatory approaches that are in line
with personaliz...

## Key facts

- **NIH application ID:** 9938603
- **Project number:** 5R01HL134811-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** SAMIA MORA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $710,610
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938603

## Citation

> US National Institutes of Health, RePORTER application 9938603, Reducing Inflammation for the Prevention of CVD: A Focus on Eicosanoid Pathways (5R01HL134811-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9938603. Licensed CC0.

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