Nitrite improves Zebrafish Cardiac Regeneration Potentially by Cytoglobin 1

DOI: 10.1016/j.freeradbiomed.2017.10.183

Cygb1 expression is necessary and/or sufficient for cardiac regeneration. DOI: 10.1016/j.freeradbiomed.2017.10.184

171 Nitrite improves Zebrafish Cardiac

172

Regeneration Potentially by Cytoglobin 1 Elizabeth Rochon1, Jianmin Xue1, Jesus Tejero1, Mark Gladwin1, and Paola Corti1 1

Metabolic Diseases Mouse Models Using

University of Pittsburgh, USA

Optical Coherence Tomography

Treatment with nitrite (NO2‒) has been shown to have a

beneficial effect on ischemia/reperfusion injury via the

production of nitric oxide (NO) and modulation of reactive oxygen/nitrogen

species

(ROS/RNS).

Nitrite

can

be

converted to NO through the action of heme globins via a nitrite reductase reaction. The role of NO2‒ and globins has

not

yet

been

investigated

in

the

context

of

heart

regeneration. Zebrafish can fully regenerate their hearts following ventricular amputation and were used a model to study the effects of hypoxia and NO2‒ treatment on heart regeneration. We hypothesize that treatment with hypoxia/ NO2‒ will improve cardiac regeneration through increased

production of NO or signaling ROS/RNS. We have found that NO2‒ /hypoxia treatment improves the rate of

cardiomyocyte

Noninvasive Retinal Optical Imaging in

proliferation

and

improves

neovascularization compared to hypoxia alone five days post amputation (dpa). Preceding these events, we observe an increase in thrombocytes (1 dpa) and neutrophils (3 dpa) migration to the injured area and a decrease in the blood clot size, suggesting that NO2‒ treatment is able to modulate

the immune response to improve healing following injury. Zebrafish Cytoglobin 1 (Cygb1) is a globin that may mediate the cardiac regenerative response to NO2‒. Our data show

that Cygb1 is expressed in the epicardium (a tissue that is known to drive the regeneration process) and its expression is increased following cardiac injury. Cygb1 may be mediating this response via its fast nitrite reductase rate

(28.6 ± 3.1 M (-1) s(-1)) in its deoxy state or oxy-Cygb1 may react with NO2- to produce RNS, modulating the immune response via ROS/RNS signaling.

Given the

Di Shao1, Weiye Song1, Ji Yi1, and Markus Bachschmid1 1

Boston University Medical Center, USA

Objectives: To evaluate retinal thickness, microvasculature, blood flow rate and oxygen metabolic rate in glutaredoxin-1 (Glrx) knock out induced metabolic disease mouse models. Methods: Twenty-week old wild type and Glrx knock out mice fed with normal chow diet were imaged. Visible-light optical coherence tomography (vis-OCT) was used to image retinal thickness and microvasulature, as well as functional parameters including retinal blood flow rate and oxygen saturation (sO2). These quantitative measurements were compared between wild type and Glrx knock out mice. Results: We observed that the retinal thickness was significantly decreased in Glrx knock out mice compared with wild type mice. Additionally, we found significant reduction in arteriovenous sO2 difference in these mice, indicating lower oxygen extraction efficiency. However, Glrx knockout mice did not exhibit any differences in retinal blood flow rate as well as the density of microvasculature. Conclusions: vis-OCT provides an unprecedented capability for high-resolution imaging of mouse retinal vessels, in venous sO2 and blood flow that may play a pivotal role in providing a noninvasive method for detection of early microvascular

patients

disorder induced retinopathy. DOI: 10.1016/j.freeradbiomed.2017.10.185

hypothesize that it is the latter, even in the context of the Our current research aims to identify the

mechanism by which nitrite treatment modulates the immune response in the healing heart and determine if

122

in

with

retinopathy.

Glutaredoixn-1 plays a very important role in metabolic

extremely low Cygb1 oxygen P50 (0.277 torr), we hypoxic heart.

changes

SfRBM 2017