# Basic and Translational Studies in Redox Regulation of Cardiovascular Physiology and Disease

> **NIH NIH R35** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $940,725

## Abstract

ABSTRACT
Our research program seeks to elucidate the chemistry, biology and translational impact of “redox switches” in
the cardiovascular system. Our work has revealed that cytochrome b5 reductase 3 (CYB5R3) operates as a
critical redox switch in the cardiovascular system by reducing substrates such heme and coenzyme Q to
modulate reactive nitrogen and oxygen species and downstream signaling. The overarching goal of this R35
research proposal is to fill four major gaps in our knowledge related to redox switches in the cardiovascular
biology. First, we will define the role(s) of the “other CYB5R” family members including CYB5R1, 2, 4, 5 and their
functions in endothelial, smooth muscle and cardiomyocytes. While expressed in these cells types, there are no
reports defining the function(s) of these enzymes in the cardiovascular system. Using new cell type specific
knockouts of CYB5R1, 2, 4, 5, we will delineate the physiological and pathophysiological role(s) of these
enzymes across endothelial, smooth muscle and cardiomyocytes and their potential function(s) in redox
signaling. Second, we aim to establish novel client proteins for the CYB5R family of enzymes using an innovative
“biopanning” approach. Utilizing a genetically modified soybean peroxidase coupled to CYB5R enzymes we will
establish new binding partners, substrates and mechanisms for these reductases. Third, using large human
data sets (i.e. n=8500 participants), we will assess if common genetic variants in CYB5R enzymes associates
with diseases such as hypertension, sickle cell disease and heart failure. Mechanistic studies will determine
functional impact of these variants on redox signaling pathways in cardiovascular cells. Forth, we will leverage
the information gained from our studies on CYB5R3 to test if a new drug we developed called “NitroQ” and test
if improves redox equilibrium and reverses hypertension, sickle cell disease and heart failure. Mechanistic
studies will elucidate key targets and downstream signaling pathways influenced by NitroQ. Collectively, these
fundamental basic, translational and therapeutic studies will provide a critical framework that will enable us to fill
these major gaps in our knowledge and improve our understanding of redox switches in cardiovascular health
and disease.

## Key facts

- **NIH application ID:** 10351500
- **Project number:** 1R35HL161177-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Adam Carl Straub
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $940,725
- **Award type:** 1
- **Project period:** 2022-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10351500

## Citation

> US National Institutes of Health, RePORTER application 10351500, Basic and Translational Studies in Redox Regulation of Cardiovascular Physiology and Disease (1R35HL161177-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10351500. Licensed CC0.

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