# Center for Redox Biology and Cardiovascular Disease

> **NIH NIH P20** · LOUISIANA STATE UNIV HSC SHREVEPORT · 2020 · $191,038

## Abstract

PROJECT SUMMARY/ABSTRACT
The present project is part of the Centers of Biomedical Research Excellence (COBRE) grant focused on
research on redox biology mechanisms of cardiovascular disease. The objective of the COBRE Center for Redox
Biology and Cardiovascular Disease is to establish a nationally recognized research and training program that
develops federally funded junior faculty research while revealing new insights into cardiovascular pathology. One
of the major goals of this COBRE program is to advance mechanistic understanding of redox biology regulation
in cardiovascular pathophysiology. To accomplish this goal, the COBRE program provides a consistent and
robust mentorship and professional development program, funding, and core facility support to junior faculty
projects investigating the redox biology mechanisms of cardiovascular disease that will be competitive for
independent federal funding. The proposed research is part of a current, funded COBRE pilot project focused
on investigating the sex-specific effects of redox imbalances on the heart. The main goal of this proposed
supplement is to expand our current studies on sexual dimorphism. We aim to elucidate, for the first time, the
direct effects of confinement-induced mental stress on the female heart, and to test whether increased mental
stress leads to alterations in critical genes involved in antioxidant pathways in the heart. Since we are facing an
unprecedented situation involving social distancing and confinement with the COVID-19 pandemic,
understanding the long-term cardiac effects of mental stress triggered by confinement is currently of great
interest. Women are at high risk of developing cardiac events in response to mental stress. Stress levels in
women have been shown to correlate with delayed recovery, recurrence, and increased mortality after a heart
attack compared with age-matched men. However, the mechanisms underlying these sex differences are not
precise. In this proposal, we plan to evaluate the direct and long-term effects of confinement stress on the female
heart, and to test whether exposure to this stressor leads to adverse outcomes in females by altering the
expression of genes involved in maintaining the redox balance in cardiomyocytes. Our preliminary data revealed
that confinement stress induces sex-specific changes in the expression of cyclin-dependent kinase inhibitor 1A
(Cdkn1A), which activates the master regulator of the intracellular antioxidant response, nuclear factor erythroid-
2-related factor 2 (Nrf2). With the support of this supplement, if awarded, we will test if Cdkn1A in the female
heart is under the direct regulation of the glucocorticoid receptor (GR), the stress hormone receptor. Also, we
will test whether changes in the levels of Cdkn1A have effects on Nrf2 downstream signaling in the heart that
may predispose females to heart disease and its complications. The results gathered in this proposal will provide
the basis for future studie...

## Key facts

- **NIH application ID:** 10154332
- **Project number:** 3P20GM121307-03S1
- **Recipient organization:** LOUISIANA STATE UNIV HSC SHREVEPORT
- **Principal Investigator:** Christopher G Kevil
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,038
- **Award type:** 3
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154332

## Citation

> US National Institutes of Health, RePORTER application 10154332, Center for Redox Biology and Cardiovascular Disease (3P20GM121307-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10154332. Licensed CC0.

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