Cardiac Response to Obstructive Sleep Apnea: Direct Effects and Preconditioning Protein in-vitro

Project Summary Obstructive sleep apnea (OSA) is known to be correlated with cardiovascular diseases (CVD), yet controlled clinical trials showed that CPAP treatment was insufficient to alleviate CVD risk in all patients. Current tools fail to identify the mechanistic pathways involved in OSA-related CVD pathophysiology, and residual CVD risk may persist despite CPAP treatment. Conversely, some studies have identified OSA as possibly protective against myocardial infarction preconditioning consequences, highlighting significant knowledge gaps in understanding the mechanisms linking OSA and CVD. This research project aims to elucidate the complex relationship between OSA and CVD through an innovative "heart-on-a-chip" platform combined with validated intermittent hypoxia (IH) protocols. Specifically, we will develop and validate physiologically relevant IH protocols using endothelial cells, comparing responses against patient tissue samples. These validated protocols will then be applied to our "heart-on-a-chip" model to investigate the direct impact of OSA-induced IH on cardiac structure and function, providing insights into OSA-specific cardiovascular diseases. Additionally, we will examine whether different patterns of OSA-associated IH can provide cardiovascular protection through preconditioning mechanisms prior to ischemic insult and identify the underlying pathways. This comprehensive approach addresses current limitations in OSA research by providing physiologically relevant in vitro models that can directly test competing hypotheses about OSA's cardiac effects. Our research has the potential to identify novel therapeutic targets and improve the clinical management of OSA patients at risk for cardiovascular complications.