Characterising extracellular vesicles populations in cardiovascular diseases

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Background: Cardiovascular diseases remain the leading cause of death around the world. Extracellular vesicles (EVs) are a group of small lipid bilayer membrane vesicles that are released from different types of cells of different sizes and are present in many body fluids. EVs play a significant role in cell-to-cell communication and have been found to be involved in cardiovascular disease development. Hypothesis and aims: We hypothesised that EVs size and concentration differed in patients with different cardiovascular diseases. The aim is to compare the EV size and concentration in different serum samples obtained from two cohort studies of patients with or without cardiovascular disease and in smooth muscle cells cultured under controlled conditions and under atherogenic stimuli of oxidized low-density lipoprotein (ox-LDL). Methods: EVs were isolated by precipitation and size exclusion chromatography from serum samples of patients with or without cardiovascular disease in two cohort studies and from human coronary artery smooth muscle cells treated under controlled and atherogenic conditions. EVs were diluted to calculate the optimised measurement of their size and concentration via nanoparticle tracking analysis. Results: In both cohort studies, EVs size and concentration in the different serum samples were not significantly different between the two groups. In EVs derived from human coronary artery smooth muscle cells cultured in the presence or absence of ox-LDL, there was no significant difference in size, but the concentration was significantly higher after atherogenic stimulation with ox-LDL. Conclusion: These data showed that EVs size and concentration were not different in all samples measured from the two cohort studies. However, this project identified a significant difference in the EVs concentration derived from human coronary artery smooth muscle cells treated under atherogenically stimulated conditions when exposed to ox-LDL. The insights gained in this study showed the potential of EVs to be a therapeutic target for cardiovascular disease development, especially atherosclerosis. These observations should be validated in a larger study to assess the potential role of EVs in the development of cardiovascular disease.