Cargando…
Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes
Cardiovascular morbidity is the leading cause of death of obstructive sleep apnea (OSA) syndrome patients. Nocturnal airway obstruction is associated with intermittent hypoxia (IH). In our previous work with cell lines, incubation with sera from OSA patients induced changes in cell morphology, NF-κB...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499466/ https://www.ncbi.nlm.nih.gov/pubmed/36142186 http://dx.doi.org/10.3390/ijms231810272 |
_version_ | 1784794997961261056 |
---|---|
author | Regev, Danielle Etzion, Sharon Haddad, Hen Gopas, Jacob Goldbart, Aviv |
author_facet | Regev, Danielle Etzion, Sharon Haddad, Hen Gopas, Jacob Goldbart, Aviv |
author_sort | Regev, Danielle |
collection | PubMed |
description | Cardiovascular morbidity is the leading cause of death of obstructive sleep apnea (OSA) syndrome patients. Nocturnal airway obstruction is associated with intermittent hypoxia (IH). In our previous work with cell lines, incubation with sera from OSA patients induced changes in cell morphology, NF-κB activation and decreased viability. A decrease in beating rate, contraction amplitude and a reduction in intracellular calcium signaling was also observed in human cardiomyocytes differentiated from human embryonic stem cells (hESC-CMs). We expanded these observations using a new controlled IH in vitro system on beating hESC-CMs. The Oxy-Cycler system was programed to generate IH cycles. Following IH, we detected the activation of Hif-1α as an indicator of hypoxia and nuclear NF-κB p65 and p50 subunits, representing pro-inflammatory activity. We also detected the secretion of inflammatory cytokines, such as MIF, PAI-1, MCP-1 and CXCL1, and demonstrated a decrease in beating rate of hESC-CMs following IH. IH induces the co-activation of inflammatory features together with cardiomyocyte alterations which are consistent with myocardial damage in OSA. This study provides an innovative approach for in vitro studies of OSA cardiovascular morbidity and supports the search for new pharmacological agents and molecular targets to improve diagnosis and treatment of patients. |
format | Online Article Text |
id | pubmed-9499466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94994662022-09-23 Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes Regev, Danielle Etzion, Sharon Haddad, Hen Gopas, Jacob Goldbart, Aviv Int J Mol Sci Article Cardiovascular morbidity is the leading cause of death of obstructive sleep apnea (OSA) syndrome patients. Nocturnal airway obstruction is associated with intermittent hypoxia (IH). In our previous work with cell lines, incubation with sera from OSA patients induced changes in cell morphology, NF-κB activation and decreased viability. A decrease in beating rate, contraction amplitude and a reduction in intracellular calcium signaling was also observed in human cardiomyocytes differentiated from human embryonic stem cells (hESC-CMs). We expanded these observations using a new controlled IH in vitro system on beating hESC-CMs. The Oxy-Cycler system was programed to generate IH cycles. Following IH, we detected the activation of Hif-1α as an indicator of hypoxia and nuclear NF-κB p65 and p50 subunits, representing pro-inflammatory activity. We also detected the secretion of inflammatory cytokines, such as MIF, PAI-1, MCP-1 and CXCL1, and demonstrated a decrease in beating rate of hESC-CMs following IH. IH induces the co-activation of inflammatory features together with cardiomyocyte alterations which are consistent with myocardial damage in OSA. This study provides an innovative approach for in vitro studies of OSA cardiovascular morbidity and supports the search for new pharmacological agents and molecular targets to improve diagnosis and treatment of patients. MDPI 2022-09-07 /pmc/articles/PMC9499466/ /pubmed/36142186 http://dx.doi.org/10.3390/ijms231810272 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Regev, Danielle Etzion, Sharon Haddad, Hen Gopas, Jacob Goldbart, Aviv Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes |
title | Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes |
title_full | Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes |
title_fullStr | Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes |
title_full_unstemmed | Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes |
title_short | Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes |
title_sort | obstructive sleep apnea syndrome in vitro model: controlled intermittent hypoxia stimulation of human stem cells-derived cardiomyocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499466/ https://www.ncbi.nlm.nih.gov/pubmed/36142186 http://dx.doi.org/10.3390/ijms231810272 |
work_keys_str_mv | AT regevdanielle obstructivesleepapneasyndromeinvitromodelcontrolledintermittenthypoxiastimulationofhumanstemcellsderivedcardiomyocytes AT etzionsharon obstructivesleepapneasyndromeinvitromodelcontrolledintermittenthypoxiastimulationofhumanstemcellsderivedcardiomyocytes AT haddadhen obstructivesleepapneasyndromeinvitromodelcontrolledintermittenthypoxiastimulationofhumanstemcellsderivedcardiomyocytes AT gopasjacob obstructivesleepapneasyndromeinvitromodelcontrolledintermittenthypoxiastimulationofhumanstemcellsderivedcardiomyocytes AT goldbartaviv obstructivesleepapneasyndromeinvitromodelcontrolledintermittenthypoxiastimulationofhumanstemcellsderivedcardiomyocytes |