The effect of sera from children with obstructive sleep apnea syndrome (Osas) on human cardiomyocytes differentiated from human embryonic stem cells

Hen Haddad, Sharon Etzion, Tatiana Rabinski, Rivka Ofir, Danielle Regev, Yoram Etzion, Jacob Gopas, Aviv Goldbart

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 ex-panded 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.

Original languageEnglish
Article number11418
JournalInternational Journal of Molecular Sciences
Volume22
Issue number21
DOIs
StatePublished - 1 Nov 2021

Keywords

  • Beating rate
  • Cardiomyocytes (CM) derived from human embryonic stem cells (hES)
  • Contractility
  • Inflammation
  • Intracellular [Ca]i signaling
  • NF‐κB
  • Obstructive sleep apnea
  • Sera

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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