Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes
| Autor: | Danielle Regev, Sharon Etzion, Hen Haddad, Jacob Gopas, Aviv Goldbart |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Sleep Apnea
Obstructive Stem Cells Organic Chemistry NF-kappa B obstructive sleep apnea intermittent hypoxia inflammation NF-κB cytokines hESC-CM human embryonic stem cells derived cardiomyocytes General Medicine Catalysis Computer Science Applications Inorganic Chemistry Cardiovascular Diseases Plasminogen Activator Inhibitor 1 Cytokines Humans Myocytes Cardiac Physical and Theoretical Chemistry Hypoxia Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 18; Pages: 10272 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms231810272 |
| Popis: | Cardiovascular morbidity is the leading cause of death of obstructive sleep apnea (OSA) syndrome patients. Nocturnal airway obstruction is associated with intermittent hypoxia (IH). In our previous work with cell lines, incubation with sera from OSA patients induced changes in cell morphology, NF-κB activation and decreased viability. A decrease in beating rate, contraction amplitude and a reduction in intracellular calcium signaling was also observed in human cardiomyocytes differentiated from human embryonic stem cells (hESC-CMs). We expanded these observations using a new controlled IH in vitro system on beating hESC-CMs. The Oxy-Cycler system was programed to generate IH cycles. Following IH, we detected the activation of Hif-1α as an indicator of hypoxia and nuclear NF-κB p65 and p50 subunits, representing pro-inflammatory activity. We also detected the secretion of inflammatory cytokines, such as MIF, PAI-1, MCP-1 and CXCL1, and demonstrated a decrease in beating rate of hESC-CMs following IH. IH induces the co-activation of inflammatory features together with cardiomyocyte alterations which are consistent with myocardial damage in OSA. This study provides an innovative approach for in vitro studies of OSA cardiovascular morbidity and supports the search for new pharmacological agents and molecular targets to improve diagnosis and treatment of patients. |
| Databáze: | OpenAIRE |
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