# GLYCINE AND N-ACETYL CYSTEINE SUPPLEMENTED DIET IMPROVES INFLAMMATORY-BASED FIBROSIS IN THE AGING HEART

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $160,000

## Abstract

PROJECT SUMMARY
The US population is aging; in a decade, 20% of people living in the US will be 65 or older. The
focus of our work is on the mechanism(s) of improving diastolic dysfunction, reducing cardiac
fibrosis and inflammation in mice treated with GlyNAC (glycine + N-Acetyl-Cysteine) with or
without DCSL1 (Dendritic Cell-Specific Intercellular Adhesion Molecule 3-Grabbing Non-integrin
ligand 1). Our overall objective is to examine functional cardiac and cellular changes in these
potential rescue approaches to reduce diastolic dysfunction and cardiac fibrosis in the aging heart.
The central hypothesis arose from our data in which we demonstrated that reactive oxygen
species and inflammation contribute to the cardiac decline via an inflammatory dependent
activation of cardiac fibrosis. We found that an increased level of MCP-1, a leukocyte
chemoattractant, causes elevated leukocyte infiltration. Infiltrating monocytes polarize into pro-
and anti-fibrotic macrophages, which further contribute to pathological fibroblast activation and
excessive collagen production. We found a significant improvement in cardiac function
accompanied by reduced fibrosis in aged mice via restoring reduced glutathione (GSH) levels (by
treating mice with GlyNAC, glycine and N-acetyl cysteine = glutathione precursors) or by reducing
macrophage polarization (via DCSL1). However, we only treated male mice with GlyNAC despite
the fact that females display worse diastolic dysfunction and more severe fibrosis than males.
Interestingly, DCSL1 treatment, which we applied to both male and female mice, only improved
female heart function. Therefore, we postulated that the treatment of male and female aged mice
with GlyNAC with or without DCSL1 may prevent or even reverse inflammatory dysfunction and
fibrosis in the heart. In SA1, we will determine the effect of the dietary and pharmacological
treatment on heart function. Specifically, we will examine vascular function, echocardiography,
mitral and aortic blood flow velocities, exercise endurance, invasive systolic, and diastolic
functions. In SA2, we will investigate the cellular and molecular mechanisms of the GlyNAC and
DCSL1 treatments. At termination, in each mouse, we will analyze macrophage and lymphocyte
polarization via flow cytometry and identify cytokines secreted by them via protein array. Finally,
collagen deposition and fibrosis will be examined. This approach is innovative and significant
because it will allow us to correlate changes in cardiac function to molecular and cellular
responses. Furthermore, our Preliminary Data shows a correlation of the mouse model with the
human aging heart.

## Key facts

- **NIH application ID:** 10284824
- **Project number:** 3R01AG059599-03S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** KATARZYNA A. CIESLIK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $160,000
- **Award type:** 3
- **Project period:** 2018-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10284824

## Citation

> US National Institutes of Health, RePORTER application 10284824, GLYCINE AND N-ACETYL CYSTEINE SUPPLEMENTED DIET IMPROVES INFLAMMATORY-BASED FIBROSIS IN THE AGING HEART (3R01AG059599-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10284824. Licensed CC0.

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