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, the cell's morphology changes, NF-kappa B 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-kappa B 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-kappa B 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.

Automated summary

The study revealed that incubation with sera from pediatric OSAS patients could lead to changes in cardiomyocyte morphology, activation of the NF-kappa B pathway, and a decrease in beating rate and viability. These findings suggest a significant connection between OSAS, systemic inflammatory signals, and cardiovascular diseases, highlighting the role of NF-kappa B-dependent inflammatory pathways in the pathogenesis of cardiovascular morbidity in OSAS. The use of human cardiomyocytes derived from embryonic stem cells in OSAS research is novel and provides a new model for studying cardiovascular pathology in this condition.