# Role of Cytoglobin in the Regulation of Vascular Tone

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $721,580

## Abstract

Abstract
Endothelium-derived relaxing factor, identified as nitric oxide (NO), is a key mediator regulating vascular tone
and blood pressure. NO mediates vascular relaxation through activation of soluble guanylate cyclase (sGC) in
the smooth muscle. While NO is synthesized by a specific well characterized NO synthase in the endothelium
(eNOS), the process of vascular NO degradation and metabolism is poorly understood. It is hypothesized that
NO degradation in the vessel wall is mediated by an O2-dependent NO dioxygenase (NOD) that oxidizes NO
to nitrate. However, the identity of the specific NO dioxygenase that serves as the main in vivo regulator of O2-
dependent NO degradation in vascular smooth muscle has remained elusive. Cytoglobin (Cgb) is a recently
discovered globin expressed in smooth muscle with unknown function. Based on our preliminary data where
we observe that: 1) Cgb is the major globin expressed in smooth muscle; and 2) knockout of Cgb greatly
prolongs NO decay, increases vascular relaxation, lowers blood pressure and systemic vascular resistance,
we hypothesize that Cgb is the major heme protein regulating the rate of O2-dependent NO metabolism
in the vessel wall, in turn profoundly modulating vascular tone. In this grant, there are 3 aims in which we
sequentially test this hypothesis, first in vascular smooth muscle cells, then in isolated vessels and finally in the
in vivo cardiovascular system with experimental measurements and computational modeling. The latter will
enable us to determine how well the process of Cgb-mediated O2-dependent NO metabolism accounts for the
measured vascular NO metabolism along with enabling prediction of the effects of modulating Cgb expression
and NOD function. Since the O2-dependent NOD function of Cgb is controlled by its rate of reduction, studies
will be performed to elucidate the process and mechanisms of Cgb reduction in smooth muscle cells, vessels
and in vivo in mice utilizing molecular knockdown, pharmacological inhibition, or other manipulation of these
reducing pathways. We will determine how modulation of the NOD function of Cgb modulates vascular tone in
normal physiology and vascular disease with studies in vessels and mice with varying Cgb expression levels
and inhibition of each of the major pathways of its reduction or specific inhibition of its NOD function. These
studies will be performed in normal mice and mice with angiotensin-induced hypertension. In these settings,
studies will be performed to measure and scavenge superoxide (O2-.) to determine how the O2-dependent
reaction of NO with Cgb compares to that of O2-. and specific attention paid to the role of the endothelium and
the coupling state of eNOS in NO metabolism. Accomplishment of this research plan will elucidate the
molecular mechanism underlying the important role of Cgb in vascular NO metabolism and provide
important insights into the regulation of vascular tone in normal physiology and cardiovascular
disease. Thi...

## Key facts

- **NIH application ID:** 9842910
- **Project number:** 5R01HL131941-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** GOVINDASAMY ILANGOVAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $721,580
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842910

## Citation

> US National Institutes of Health, RePORTER application 9842910, Role of Cytoglobin in the Regulation of Vascular Tone (5R01HL131941-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842910. Licensed CC0.

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