Testing Coagulation Potential of Extracellular Vesicles Derived from Aortic Stenosis Patients on Human Cardiac Spheroids

Sammanfattning: Cardiovascular diseases have always been the leading cause of global morbidity and mortality. Aortic stenosis, which is a kind of cardiovascular disease has a high prevalence in elderlies that are 75 years and older. Currently, the only available treatment would be valve replacement surgery. Recently, a few studies have risen regarding the potential of extracellular vesicles to reduce the effects of aortic stenosis, hence allowing patients to opt for a non-life-threatening treatment in comparison to a surgical one. The goal within this study is to determine the pro-coagulability of extracellular vesicles (EVs) that were endogenously derived from human blood (patients and healthy individuals) and their effect on the coagulation cascade. This study was performed on cardiac spheroids that were formed through seeding human aortic endothelial cells in an ultra-low attachment 96-well plate for 96 hours. Spheroids were challenged with tumour necrosis factor-alpha (TNFα) for 24 hours prior to EVs incubation for 48 and 72 hours. The effects of EVs on these spheroids were observed in terms of their ability to induce tissue factor activity. There was no significant difference in the tissue factor activity between spheroids incubated with patient derived EVs or healthy individual derive EVs irrespective of TNFα challenge. To conclude, the results of this study were not significant to stipulate that extracellular vesicles are procoagulant. Hence, further research regarding their ability to reduce or rescue the effects of cardiovascular diseases needs to be performed.