# Vascular dysfunction in coronary microcirculation

> **NIH NIH R01** · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · 2024 · $622,223

## Abstract

Abstract
Cardiovascular disease causes 34% of all deaths in the United States and 17.6 million
Americans suffer from coronary heart disease (CHD). Of these, 8.5 million experience
myocardial infarction. Although we have made significant progress in understanding the
mechanisms of reperfusion injury of heart, we are yet to find an effective intervention to
alleviate I/R injury. Nitric oxide (NO) plays a major role in relaxation of coronary
microcirculation that is important to transport oxygen and nutrients to myocardial tissue. It
has been demonstrated that nitric oxide synthase (eNOS), the enzyme that generates NO
in the vascular endothelium is altered in I/R and produces deleterious superoxide anion
radical, which not only depletes NO by reacting with it, but also produces more harmful
reactive nitrogen species. Intriguingly, in our preliminary studies we found that eNOS is
glutathionylated and progressively lost in the myocardial tissue following I/R. We
hypothesize that eNOS undergoes S-glutathionylation during I/R that induces its
chaperone mediated autophagy, resulting in irreversible loss of NO production that affects
coronary microcirculation and perfusion resulting in myocardial infarction (MI) in I/R. In
Aim 1 we will investigate the mechanism of loss of vascular eNOS due to S-
glutathionylation. In Aim 2, we will investigate the specific type of autophagy involved in
eNOS disappearance; and in Aim 3 we will elucidate the eNOS autophagy and evaluate
whether deglutathionylation by thioredoxin would ameliorate reperfusion injury, using a
variety of transgenic and knockout mice models. Our proposed research will provide a
clear understanding of the role of coronary vascular mechanism of loss of eNOS in I/R.
The results of this study may provide significant insight into clinical management of
myocardial infarction and develop new intervention for treatment of reperfusion injury.

## Key facts

- **NIH application ID:** 10742936
- **Project number:** 5R01HL157128-03
- **Recipient organization:** TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
- **Principal Investigator:** KUMUDA C DAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $622,223
- **Award type:** 5
- **Project period:** 2021-12-10 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10742936

## Citation

> US National Institutes of Health, RePORTER application 10742936, Vascular dysfunction in coronary microcirculation (5R01HL157128-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10742936. Licensed CC0.

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