# The Microvascular Aging and Eicosanoids - Women's Evaluation of Systemic Aging Tenacity (MAE-WEST) ("You are never too old to become younger!") Specialized Center for Research Excellence (SCORE)

> **NIH NIH U54** · CEDARS-SINAI MEDICAL CENTER · 2020 · $1,767,973

## Abstract

Project Abstract – MAE-WEST SCORE Overall
Women age differently than men across the lifespan, culminating in a female predominance in morbid chronic
diseases such as heart failure with preserved ejection fraction, Alzheimer’s disease and related dementias, and
chronic kidney disease. Women also tend to develop multi-organ syndromes (heart-brain, heart-kidney) more
frequently than men. The mechanisms underlying sex-specific differences in multi-organ dysfunction remain
poorly understood. Prior work indicates that women exhibit accelerated microvascular aging, a process
implicated in disorders of the heart, brain, and kidney. In this context, systemic inflammation has emerged as a
primary driver of both microvascular dysfunction and the development of these chronic disease states.
Preliminary data from our group indicates that eicosanoids, a diverse group of bioactive lipids that serve as the
upstream mediators of systemic inflammation, can influence endothelial cell function, exhibit sexual dimorphism
in circulating plasma, and are related to certain vascular phenotypes. Given these findings, we hypothesize that
sexual dimorphism in both local and systemic eicosanoid variation contributes to sex differences in microvascular
dysfunction and, in turn, to sex differences in age-related multi-organ disease. Motivated by our early findings
and the critical need to understand the determinants and drivers of sex differences in age-related disease
outcomes, we propose to create the Microvascular Aging and Eicosanoids –Women’s Evaluation of Systemic
aging Tenacity (MAE-WEST) Specialized Center of Research Excellence (SCORE) on Sex Differences.
Leveraging our collective expertise, we plan to advance the understanding of sex-specific molecular drivers of
chronic microvascular and end-organ disease through 3 foundational projects. In Project 1, we will examine
longitudinal variation in circulating eicosanoid levels in relation to age-related alterations in microvascular
function in end-organ (cardiovascular, neurocognitive, renal) disease traits in 2 large community cohorts. In
Project 2, we will prospectively enroll and deeply phenotype a cohort of women and men to assess the relation
of eicosanoids with organ-specific as well as global burden of microvascular disease, as well as their response
to a trial of intensive medical therapy with FDA-approved agents (statins and ACEi/ARB). Finally, in Project 3,
we will study the mechanistic role of sex-specific eicosanoid signaling on human endothelial cell function and on
microvascular function in experimental models of organ-specific disease as well as whole organism aging. As
an integral part of this SCORE, we will establish a Career Enhancement Center that will provide robust training
and mentorship for trainees and junior investigators. Collectively, this highly collaborative and innovative SCORE
aims to transform our understanding of sex differences in microvascular and chronic multi-organ diseases and,
in tu...

## Key facts

- **NIH application ID:** 9854799
- **Project number:** 1U54AG065141-01
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Cathleen Noel Bairey Merz
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,767,973
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854799

## Citation

> US National Institutes of Health, RePORTER application 9854799, The Microvascular Aging and Eicosanoids - Women's Evaluation of Systemic Aging Tenacity (MAE-WEST) ("You are never too old to become younger!") Specialized Center for Research Excellence (SCORE) (1U54AG065141-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9854799. Licensed CC0.

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