The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells

Obstructive sleep apnea syndrome (OSAS) patients suffer from cardiovascular morbidity, which is the leading cause of death in this disease. Based on our previous work with transformed cell lines and primary rat cardiomyocytes, we determined that upon incubation with sera from pediatric OSAS patients...

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Autores principales:	Hen Haddad, Sharon Etzion, Tatiana Rabinski, Rivka Ofir, Danielle Regev, Yoram Etzion, Jacob Gopas, Aviv Goldbart
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	obstructive sleep apnea sera inflammation NF-κB cardiomyocytes (CM) derived from human embryonic stem cells (hES) intracellular [Ca<sup>2+</sup>]<sub>i</sub> signaling Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/e025f904c06e4e74bc4c90392ffc6902
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spelling	oai:doaj.org-article:e025f904c06e4e74bc4c90392ffc69022021-11-11T16:53:25ZThe Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells10.3390/ijms2221114181422-00671661-6596https://doaj.org/article/e025f904c06e4e74bc4c90392ffc69022021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11418https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Obstructive sleep apnea syndrome (OSAS) patients suffer from cardiovascular morbidity, which is the leading cause of death in this disease. Based on our previous work with transformed cell lines and primary rat cardiomyocytes, we determined that upon incubation with sera from pediatric OSAS patients, the cell’s morphology changes, NF-κB pathway is activated, and their beating rate and viability decreases. These results suggest an important link between OSAS, systemic inflammatory signals and end-organ cardiovascular diseases. In this work, we confirmed and expanded these observations on a new in vitro system of beating human cardiomyocytes (CM) differentiated from human embryonic stem cells (hES). Our results show that incubation with pediatric OSAS sera, in contrast to sera from healthy children, induces over-expression of NF-κB p50 and p65 subunits, marked reduction in CMs beating rate, contraction amplitude and a strong reduction in intracellular calcium signal. The use of human CM cells derived from embryonic stem cells has not been previously reported in OSAS research. The results further support the hypothesis that NF-κB dependent inflammatory pathways play an important role in the evolution of cardiovascular morbidity in OSAS. This study uncovers a new model to investigate molecular and functional aspects of cardiovascular pathology in OSAS.Hen HaddadSharon EtzionTatiana RabinskiRivka OfirDanielle RegevYoram EtzionJacob GopasAviv GoldbartMDPI AGarticleobstructive sleep apneaserainflammationNF-κBcardiomyocytes (CM) derived from human embryonic stem cells (hES)intracellular [Ca<sup>2+</sup>]<sub>i</sub> signalingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11418, p 11418 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	obstructive sleep apnea sera inflammation NF-κB cardiomyocytes (CM) derived from human embryonic stem cells (hES) intracellular [Ca<sup>2+</sup>]<sub>i</sub> signaling Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	obstructive sleep apnea sera inflammation NF-κB cardiomyocytes (CM) derived from human embryonic stem cells (hES) intracellular [Ca<sup>2+</sup>]<sub>i</sub> signaling Biology (General) QH301-705.5 Chemistry QD1-999 Hen Haddad Sharon Etzion Tatiana Rabinski Rivka Ofir Danielle Regev Yoram Etzion Jacob Gopas Aviv Goldbart The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells
description	Obstructive sleep apnea syndrome (OSAS) patients suffer from cardiovascular morbidity, which is the leading cause of death in this disease. Based on our previous work with transformed cell lines and primary rat cardiomyocytes, we determined that upon incubation with sera from pediatric OSAS patients, the cell’s morphology changes, NF-κB pathway is activated, and their beating rate and viability decreases. These results suggest an important link between OSAS, systemic inflammatory signals and end-organ cardiovascular diseases. In this work, we confirmed and expanded these observations on a new in vitro system of beating human cardiomyocytes (CM) differentiated from human embryonic stem cells (hES). Our results show that incubation with pediatric OSAS sera, in contrast to sera from healthy children, induces over-expression of NF-κB p50 and p65 subunits, marked reduction in CMs beating rate, contraction amplitude and a strong reduction in intracellular calcium signal. The use of human CM cells derived from embryonic stem cells has not been previously reported in OSAS research. The results further support the hypothesis that NF-κB dependent inflammatory pathways play an important role in the evolution of cardiovascular morbidity in OSAS. This study uncovers a new model to investigate molecular and functional aspects of cardiovascular pathology in OSAS.
format	article
author	Hen Haddad Sharon Etzion Tatiana Rabinski Rivka Ofir Danielle Regev Yoram Etzion Jacob Gopas Aviv Goldbart
author_facet	Hen Haddad Sharon Etzion Tatiana Rabinski Rivka Ofir Danielle Regev Yoram Etzion Jacob Gopas Aviv Goldbart
author_sort	Hen Haddad
title	The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells
title_short	The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells
title_full	The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells
title_fullStr	The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells
title_full_unstemmed	The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells
title_sort	effect of sera from children with obstructive sleep apnea syndrome (osas) on human cardiomyocytes differentiated from human embryonic stem cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e025f904c06e4e74bc4c90392ffc6902
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The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells

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