# Stress-stimulated immune profiles and cardiometabolic risk during the menopausal transition

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $272,125

## Abstract

PROJECT SUMMARY
 Altered immune function, and in particular systemic inflammation, has been repeatedly associated with
exposure to psychosocial stress and with increased risk for aging-related disease, but the mechanisms
underlying these associations are unclear. The long-term goal of this research is to help elucidate the immune
mechanisms linking psychosocial stress with aging-related and, in particular, cardiometabolic disease. The
overall objective of this application is to determine the extent to which the levels of multiple immune mediators
coordinately change in response to stress and predict cardiometabolic risk in perimenopausal women, an aging
population characterized by high stress burden, declining estradiol levels, and dramatically increasing
cardiometabolic risk. The central hypothesis is that stress during the perimenopause triggers systemic changes
in the levels of multiple cytokines and other circulating molecules, and these systemic changes act in concert
with declining estradiol levels to increase cardiometabolic risk. Consequently, the rationale of this application
is that determining the levels of multiple circulating markers and their coordinated responses to stress during
the perimenopause can yield novel, composite (multi-marker) predictors of cardiometabolic disease in aging
women. The central hypothesis will be tested by pursuing two specific aims: 1) Determine how stress
modulates immune mediators and pathways in aging perimenopausal women; and 2) Identify multi-marker
predictors of cardiometabolic worsening during the menopausal transition. To accomplish these aims, the
proposed research will use blood plasma previously collected – both at baseline rest and post-laboratory
stress – in a well-characterized cohort of 151 perimenopausal women with already documented longitudinal
measures of vascular and metabolic function. Plasma at both collection timepoints will be analyzed using
quantitative cytokine arrays to profile 80 circulating markers involved in processes relevant for cardiometabolic
disease, such as inflammation, metabolic regulation, and coagulation. The research proposed in this
application is innovative because it will for the first time perform extensive, stress-stimulated cytokine profiling
during the menopausal transition, a period characterized by high stress burden, changing hormonal and
immune milieu, and increasing cardiometabolic risk, thus being uniquely positioned to address these critical
relational gaps in knowledge. The proposed research is significant because it leverages already available
biological material and extensive metadata to identify new molecular targets and risk markers and to ultimately
enhance early interventions for cardiometabolic disease in aging women.

## Key facts

- **NIH application ID:** 10510682
- **Project number:** 1R21AG078630-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** David R. Rubinow
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $272,125
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510682

## Citation

> US National Institutes of Health, RePORTER application 10510682, Stress-stimulated immune profiles and cardiometabolic risk during the menopausal transition (1R21AG078630-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10510682. Licensed CC0.

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