# Exercise training-enhanced reactive oxygen species as protective mechanisms in the coronary microcirculation

> **NIH NIH R01** · TEXAS A&M UNIVERSITY · 2021 · $649,984

## Abstract

Project Summary
Regular exercise is a proven, powerful and cost-effective intervention for the treatment and secondary
prevention of coronary artery disease. However, a detailed understanding of the fundamental cellular and
molecular mechanisms that underlie exercise-induced cardioprotection are lacking, limiting the development of
effective new therapeutic strategies for diseased patients. Despite recent advances in the appreciation of
reactive oxygen species (ROS) as critical regulators of cell signaling, the details of the specific contributions of
these molecules to physiologic signaling and functional adaptions in the vascular system remain to be
elucidated. This is particularly true in the coronary microcirculation where studies determining the contributions
of ROS in the control of blood flow are sparse. The proposed studies will utilize a combination of in vitro and in
vivo approaches to determine how exercise-induced adaptations in ROS signaling affect vascular reactivity
and coronary blood flow into both control and ischemic myocardium, an area that has been largely unexplored
in the coronary circulation. The overarching hypothesis is that ROS play a critical and protective role in the
exercise training-induced restoration of vasodilation responses in the coronary microcirculation and thereby
enhances perfusion and contractile function of the at-risk myocardium. Aim 1 will determine exercise training-
induced adaptations in ROS production in hearts subjected to chronic coronary artery occlusion. Aim 2 will
determine the effects of exercise training on the expression and subcellular localization of candidate sources of
ROS production and associated regulatory subunit proteins in microvascular endothelium of hearts subjected
to chronic coronary artery occlusion. Aim 3 will identify the adaptations by which exercise training promotes
downstream signaling pathway(s) for ROS-mediated dilation in arterioles isolated from hearts subjected to
chronic coronary artery occlusion. Aim 4 will identify the signaling mechanisms by which exercise training
enhances regional perfusion and myocardial contractile function at rest and during dobutamine-induced
myocardial stress in hearts subjected to chronic coronary occlusion. These studies are of high impact since the
knowledge gained will provide novel insight into the protective role of ROS in the cardiovascular system. The
proposed studies will provide important new information with significant mechanistic insight into human
ischemic heart disease and identify the role of ROS signaling in the control of coronary blood flow in health,
disease, and exercise adaptation.

## Key facts

- **NIH application ID:** 10146456
- **Project number:** 5R01HL139903-04
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** CRISTINE L HEAPS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $649,984
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146456

## Citation

> US National Institutes of Health, RePORTER application 10146456, Exercise training-enhanced reactive oxygen species as protective mechanisms in the coronary microcirculation (5R01HL139903-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10146456. Licensed CC0.

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