# MitoQ supplementation for restoring aerobic exercise training effects on endothelial function in postmenopausal women

> **NIH NIH R56** · UNIVERSITY OF COLORADO DENVER · 2022 · $430,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Endothelial dysfunction is a critical factor in the etiology of age-associated cardiovascular disease (CVD), the
leading cause of death in postmenopausal women. Regular aerobic exercise (AE) enhances macro- and
micro-vascular endothelial function in older men by reducing oxidative stress and preserving nitric oxide (NO)
bioavailability, however, similar AE training improvements are diminished or absent in estrogen (E2)-deficient
postmenopausal women. NO-mediated endothelial function and oxidative stress are improved with AE training
in postmenopausal women treated with E2, suggesting an essential role of E2 in endothelial adaptations to AE
in women. Clinical use of E2 is contraindicated for this purpose, thus establishing alternative pharmacological
approaches that could be administered as a substitute for E2 to transduce AE signaling for vascular endothelial
benefits and reducing CVD risk in E2-deficient postmenopausal women is biomedically important. The
mitochondrial-targeted antioxidant MitoQ may be an alternative to E2 for restoring AE-endothelial signaling in
E2-deficient postmenopausal women given its recently established effectiveness for reducing reactive oxygen
species (ROS) and oxidative stress and improving endothelial function in that population. Accordingly, the
overall aim of this application is to assess the efficacy of a 12-week randomized controlled trial of moderate
intensity AE training combined with oral MitoQ (20 mg/d) compared to AE+oral placebo (PL) or No AE+MitoQ
on macrovascular (brachial artery flow-mediated dilation; FMDBA) and microvascular (forearm blood flow
response to intra-brachial infusion of acetylcholine; FBFAch) endothelial function in healthy E2-deficient
postmenopausal women. Mechanistic insight related to NO bioavailability, mitochondrial function,
ROS/oxidative stress, and the influence of “circulating factors” will also be obtained. We hypothesize that
AE+MitoQ will improve both FMDBA and FBFAch > AE+PL and > No AE+MitoQ, and that No AE+MitoQ will
improve FMDBA and FBFAch > AE+PL. The greater improvements in endothelial function with AE+MitoQ vs.
both AE+PL and No AE+MitoQ, and with No AE+MitoQ vs. AE+PL will be mediated by greater improvements
in NO bioavailability, mitochondrial function, and mitochondrial and whole cell ROS-related suppression of
endothelial function linked, at least in part, to changes in “circulating factors”. The expected results from this
study will establish the efficacy of MitoQ for restoring AE-endothelial signaling in E2-deficient postmenopausal
women, and will provide the foundation for development of evidence-based guidelines for sex-specific AE
programs for improving vascular health and preventing CVD in postmenopausal women.

## Key facts

- **NIH application ID:** 10686453
- **Project number:** 1R56AG072094-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kerrie Moreau
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $430,000
- **Award type:** 1
- **Project period:** 2022-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10686453

## Citation

> US National Institutes of Health, RePORTER application 10686453, MitoQ supplementation for restoring aerobic exercise training effects on endothelial function in postmenopausal women (1R56AG072094-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10686453. Licensed CC0.

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