Dataset Information

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

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 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.

SUBMITTER: Haddad H

PROVIDER: S-EPMC8584070 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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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.

Haddad Hen H Etzion Sharon S Rabinski Tatiana T Ofir Rivka R Regev Danielle D Etzion Yoram Y Gopas Jacob J Goldbart Aviv A

International journal of molecular sciences 20211022 21

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 ...[more]

PMID: 34768848

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Project description:ObjectiveTo assess the macular retina and choroidal thickness change in patients with obstructive sleep apnea-hypopnea syndrome (OSAS) with no significant symptoms and pathological changes in the fundus using spectral domain-optical coherence tomography.MethodsThis prospective, observational case-control study consisted of 53 eyes of 53 patients with OSAS and 12 eyes of 12 age-matched controls. Macular and choroidal thicknesses were measured by optical coherence tomography.ResultsThe foveal and nasal macular thicknesses were significantly different between four groups (P=0.001, P=0.016). The foveal thickness of the control group was significantly thinner than that of the severe group (P=0.000). The nasal macular thickness of the control group was significantly thinner than that of the severe group (P=0.008). A significant correlation was found between oxygen desaturation index (ODI) and macular center thickness (r=0.357, R(2)=0.127, P=0.004), with an ODI coefficient of 0.457 (P=0.004). Similarly, a significant correlation was found between ODI and nasal macular thickness (r=0.265, R(2)=0.070, P=0.033), with an ODI coefficient of 0.233 (P=0.033). The subfoveal choroidal thickness was significantly different among the groups (F=3.657, P=0.017). The subfoveal choroidal thickness of the severe group was significantly thinner than that of the control group, mild group, and moderate group (P=0.023, 0.006, and 0.036, respectively). The choroidal thickness 1 mm nasal to the fovea was significantly different between the groups after correcting for age and diopter (F=3.411, P=0.023). The choroidal thickness 1 mm nasal to the fovea was significantly thinner in the severe group compared with the control group and mild group (P=0.013 and 0.010, respectively). Choroidal thickness was significantly correlated with diopter (r=0.520, R(2)=0.270, P<0.001), with a coefficient of 0.327 (P<0.001), and with ODI (r=0.520, R(2)=0.165, P=0.001), with a coefficient of -0.370 (P=0.001).ConclusionsOSAS patients showed decreased foveal and nasal macular thickness, similar to the subfoveal and nasal choroidal thickness. These findings suggest that, because of intermittent hypoxia, OSAS might change the retinal and choroidal blood supply.

Project description:Background: Notopterygium incisum K.C. Ting ex H.T. Chang, a synonym of Hansenia weberbaueriana (Fedde ex H. Wolff) Pimenov & Kljuykov, is an anti-inflammatory medicinal plant. Although abrnotopterol has been reported to be its primary active metabolite, the other metabolites and their mechanisms of action remain unclear. This study aims to investigate the potential mechanisms by which its active metabolites treat Obstructive Sleep Apnea Syndrome (OSAS) through network analysis and experimental assessment. Methods: The metabolites and potential targets of Notopterygium incisum were extracted from public databases. We searched for OSAS-related genes in the Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Cytoscape 3.9.0 was used to construct the drug-target-disease network and screen for hub genes. Human bronchial epithelial (HBE) cells were cultivated in normoxia and chronic intermittent hypoxia (CIH) medium for 24 h. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) were quantified using enzyme-linked immunosorbent assay (ELISA). Prostaglandin-endoperoxide synthase 2(PTGS2) mRNA was detected using RT-qPCR, while PTGS2 and nuclear factor-kappa B (NF-κB) proteins were identified using Western blot analysis. Co-Immunoprecipitation (CoIP) and Western blotting were utilized to evaluate the ubiquitination of PTGS2 in HBE cells. Results: Pterostilbene and notopterol, isolated from Notopterygium incisum, had potential therapeutic effects on OSAS. The PTGS2 and estrogen receptor alpha (ESR1) hub genes were associated with OSAS. The pathway enrichment analysis focuses on the NF-κB, apoptosis, and HIF-1A pathways. In response to CIH, pterostilbene and notopterol decreased IL-6, TNF-α, and PGE2 levels. The NF-κB pathway was activated by an increase in PTGS2 levels. Pterostilbene promoted proteasome-mediated ubiquitination of PTGS2 protein and reduced PTGS2 levels, inhibiting the NF-κB pathway. Conclusion: This study reveals the active metabolites of Notopterygium incisum and hub genes involved in treating OSAS, which provide a basis for the follow-up development and exploitation of the botanical drug.

Dataset Information

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

Publications

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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