# Sex Differences in Chronic and Acute Vascular Responses to Aerobic Exercise in Older Adults

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2020 · $190,625

## Abstract

PROJECT SUMMARY
Cardiovascular disease (CVD) is the leading cause of death in the U.S. in both men and women. Although
biological sex is an important determinant of CVD pathophysiology, a major knowledge gap remains regarding
sex differences in CVD prevention and treatment. A key early event in CVD development is endothelial
dysfunction, characterized by impaired flow-mediated dilation (FMD). Aging progressively impairs endothelial
function which independently predicts CVD progression and events. Therefore, strategies to optimize endothelial
function in aging are clinically important. Regular aerobic exercise ameliorates endothelial dysfunction in healthy
older men, but the data in healthy postmenopausal women are inconsistent with many studies showing no effect.
The mechanisms underlying these sex disparities are unknown. Higher intensity exercise is thought to be
required for chronic endothelial adaptations in postmenopausal women, but this has not been investigated. We
have recently developed a novel exercise strategy by adapting high intensity interval training (HIIT) on a non-
weight-bearing all-extremity (NWA) ergometer. Our innovative NWA-HIIT can be implemented in a larger portion
of the aging population because it allows compensation for lower extremity musculoskeletal problems. The
primary objective of this grant application is to examine sex differences in acute and chronic endothelial
responses to NWA-HIIT in older men vs. postmenopausal women. Our overarching hypothesis is that acute and
chronic endothelial responsiveness to aerobic exercise is influenced by sex in healthy aging and acute
endothelial responses to exercise will be predictive of chronic endothelial adaptations. To examine sex
differences in chronic exercise adaptations, brachial artery FMD will be determined at baseline, after an 8-week
control period and after 8-week NWA-HIIT. To examine sex differences in the acute response to exercise, FMD
will be determined at pre-exercise, the end of a single session of NWA-HIIT and after 1-hour and 24-hours post-
exercise. The acute responses to NWA-HIIT will be measured in both the untrained and trained state (i.e., at
baseline and after 8-week NWA-HIIT). To gain mechanistic insight, we will determine: 1) protein/mRNA levels of
key factors in endothelial cells biopsied using a state-of-the-art endovascular technique and peripheral blood
mononuclear cells (PBMCs) and 2) circulating factors in blood known to be important for endothelial function.
This novel translational application will significantly impact the field by: 1) Addressing a fundamental gap in
knowledge regarding how sex influences the impact of acute and chronic aerobic exercise on endothelial function
in older adults; 2) Providing preliminary mechanistic insight into sex differences regarding in vivo
systemic/cellular/molecular adaptations to exercise in older adults by studying endothelial cells, PBMCs and key
factors in blood; and 3) Forming the foundation for fut...

## Key facts

- **NIH application ID:** 9999423
- **Project number:** 5R21AG063143-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Demetra Christou
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,625
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999423

## Citation

> US National Institutes of Health, RePORTER application 9999423, Sex Differences in Chronic and Acute Vascular Responses to Aerobic Exercise in Older Adults (5R21AG063143-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999423. Licensed CC0.

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