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sGC Activity and Regulation of Blood Flow in a Zebrafish Model System
Soluble guanylyl cyclase (sGC) protein is a heterodimer formed by two subunits encoded by GUCY1A1 and GUCY1B1 genes. The chromosomal locus 4q32.1 harbors both of these genes, which has been previously significantly associated with coronary artery disease, myocardial infarction, and high blood pressu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946990/ https://www.ncbi.nlm.nih.gov/pubmed/33716783 http://dx.doi.org/10.3389/fphys.2021.633171 |
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author | Vishnolia, Krishan K. Rakovic, Aleksandar Hoene, Celine Tarhbalouti, Karim Aherrahrou, Zouhair Erdmann, Jeanette |
author_facet | Vishnolia, Krishan K. Rakovic, Aleksandar Hoene, Celine Tarhbalouti, Karim Aherrahrou, Zouhair Erdmann, Jeanette |
author_sort | Vishnolia, Krishan K. |
collection | PubMed |
description | Soluble guanylyl cyclase (sGC) protein is a heterodimer formed by two subunits encoded by GUCY1A1 and GUCY1B1 genes. The chromosomal locus 4q32.1 harbors both of these genes, which has been previously significantly associated with coronary artery disease, myocardial infarction, and high blood pressure. Blood pressure is influenced by both the environment and genetics and is complemented by several biological pathways. The underlying mechanisms associated with this locus and its genes still need to be investigated. In the current study, we aimed to establish the zebrafish as a model organism to investigate the mechanisms surrounding sGC activity and blood pressure. A zebrafish mutant gucy1a1 line was generated using the CRISPR-Cas9 system by inducing a 4-bp deletion frameshift mutation. This mutation resulted in a reduction of gucy1a1 expression in both heterozygote and homozygote zebrafish. Blood flow parameters (blood flow, arterial pulse, linear velocity, and vessel diameter) investigated in the gucy1a1 mutants showed a significant increase in blood flow and linear velocity, which was augmented in the homozygotes. No significant differences were observed for the blood flow parameters measured from larvae with individual morpholino downregulation of gucy1a1 and gucy1b1, but an increase in blood flow and linear velocity was observed after co-morpholino downregulation of both genes. In addition, the pharmacological sGC stimulator BAY41-2272 rescued the impaired cGMP production in the zebrafish gucy1a1(±) mutant larvae. Downregulation of cct7 gene did not show any significant difference on the blood flow parameters in both wild-type and gucy1a1(±) background larvae. In summary, we successfully established a zebrafish platform for investigating sGC-associated pathways and underlying mechanisms in depth. This model system will have further applications, including for potential drug screening experiments. |
format | Online Article Text |
id | pubmed-7946990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79469902021-03-12 sGC Activity and Regulation of Blood Flow in a Zebrafish Model System Vishnolia, Krishan K. Rakovic, Aleksandar Hoene, Celine Tarhbalouti, Karim Aherrahrou, Zouhair Erdmann, Jeanette Front Physiol Physiology Soluble guanylyl cyclase (sGC) protein is a heterodimer formed by two subunits encoded by GUCY1A1 and GUCY1B1 genes. The chromosomal locus 4q32.1 harbors both of these genes, which has been previously significantly associated with coronary artery disease, myocardial infarction, and high blood pressure. Blood pressure is influenced by both the environment and genetics and is complemented by several biological pathways. The underlying mechanisms associated with this locus and its genes still need to be investigated. In the current study, we aimed to establish the zebrafish as a model organism to investigate the mechanisms surrounding sGC activity and blood pressure. A zebrafish mutant gucy1a1 line was generated using the CRISPR-Cas9 system by inducing a 4-bp deletion frameshift mutation. This mutation resulted in a reduction of gucy1a1 expression in both heterozygote and homozygote zebrafish. Blood flow parameters (blood flow, arterial pulse, linear velocity, and vessel diameter) investigated in the gucy1a1 mutants showed a significant increase in blood flow and linear velocity, which was augmented in the homozygotes. No significant differences were observed for the blood flow parameters measured from larvae with individual morpholino downregulation of gucy1a1 and gucy1b1, but an increase in blood flow and linear velocity was observed after co-morpholino downregulation of both genes. In addition, the pharmacological sGC stimulator BAY41-2272 rescued the impaired cGMP production in the zebrafish gucy1a1(±) mutant larvae. Downregulation of cct7 gene did not show any significant difference on the blood flow parameters in both wild-type and gucy1a1(±) background larvae. In summary, we successfully established a zebrafish platform for investigating sGC-associated pathways and underlying mechanisms in depth. This model system will have further applications, including for potential drug screening experiments. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7946990/ /pubmed/33716783 http://dx.doi.org/10.3389/fphys.2021.633171 Text en Copyright © 2021 Vishnolia, Rakovic, Hoene, Tarhbalouti, Aherrahrou and Erdmann. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Vishnolia, Krishan K. Rakovic, Aleksandar Hoene, Celine Tarhbalouti, Karim Aherrahrou, Zouhair Erdmann, Jeanette sGC Activity and Regulation of Blood Flow in a Zebrafish Model System |
title | sGC Activity and Regulation of Blood Flow in a Zebrafish Model System |
title_full | sGC Activity and Regulation of Blood Flow in a Zebrafish Model System |
title_fullStr | sGC Activity and Regulation of Blood Flow in a Zebrafish Model System |
title_full_unstemmed | sGC Activity and Regulation of Blood Flow in a Zebrafish Model System |
title_short | sGC Activity and Regulation of Blood Flow in a Zebrafish Model System |
title_sort | sgc activity and regulation of blood flow in a zebrafish model system |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946990/ https://www.ncbi.nlm.nih.gov/pubmed/33716783 http://dx.doi.org/10.3389/fphys.2021.633171 |
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