Abstract Thu168: Disrupted Circadian Rhythms Alter Exosomal Biophysical Signalling Impacting Cardiovascular Health

Introduction: Circadian rhythms play a crucial role in regulating cardiovascular function, with disruptions linked to increased risk of cardiovascular diseases. Recent research has uncovered a novel mechanism by which circadian rhythms impact cardiovascular health through the modulation of exosomal signaling from cardiomyocytes. However, the impact of circadian disruption on exosomal signaling and cardiovascular health remains unexplored. Research Questions: What’s the temporal effect of circadian disruption on exosomal kinetics and biophysical signalling and their impact on neighboring stromal cells, contributing to cardiovascular health? Aims: This research aims to investigate how circadian rhythms, particularly BMAL1, regulate cardiomyocyte-derived exosomal biophysical properties, uptake kinetics, and signaling, and assess their impact on cardiovascular health during circadian disruption. Methods: Cardiomyocytes were cultured under controlled circadian conditions, and exosomes were isolated at different time points. Biophysical properties, including elasticity and uptake kinetics, were analyzed using atomic force microscopy and fluorescence assays. BMAL1 knockdown was performed using siRNA to disrupt circadian rhythms. Exosomal signaling effects on target cells were assessed via co-culture experiments, and data correlations with circadian patterns were statistically evaluated. Results: Cardiomyocytes secrete exosomes following a distinct biophysical pattern correlated with circadian rhythm. These exosomes exhibit unique temporal elasticity, reflecting their dynamic biophysical nature, which influences their uptake kinetics and effects on target cells. The circadian clock genes, particularly BMAL1, appear to play a critical role in regulating this exosomal signaling. Disruption of circadian rhythms through BMAL1 knockdown leads to a loss in the biophysical pattern of cardiomyocyte-derived exosomes. Conclusion: This study emphasizes the critical role of circadian rhythms, particularly BMAL1, in regulating cardiomyocyte-derived exosomal biophysical properties and signaling. Circadian disruption alters these patterns, potentially impacting cardiovascular health, emphasizing the importance of maintaining circadian integrity for cardiac function.