TY - JOUR
T1 - The effect of sera from children with obstructive sleep apnea syndrome (Osas) on human cardiomyocytes differentiated from human embryonic stem cells
AU - Haddad, Hen
AU - Etzion, Sharon
AU - Rabinski, Tatiana
AU - Ofir, Rivka
AU - Regev, Danielle
AU - Etzion, Yoram
AU - Gopas, Jacob
AU - Goldbart, Aviv
N1 - Funding Information:
Funding: This work was supported by the Israel Science Foundation (ISF) No. 1344/15
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
KW - Beating rate
KW - Cardiomyocytes (CM) derived from human embryonic stem cells (hES)
KW - Contractility
KW - Inflammation
KW - Intracellular [Ca]i signaling
KW - NF‐κB
KW - Obstructive sleep apnea
KW - Sera
UR - http://www.scopus.com/inward/record.url?scp=85117361531&partnerID=8YFLogxK
U2 - 10.3390/ijms222111418
DO - 10.3390/ijms222111418
M3 - Article
C2 - 34768848
AN - SCOPUS:85117361531
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 21
M1 - 11418
ER -