Abstract/Summary

Extracellular vesicles (EVs) are small membrane derived vesicles released by activated or dying cells, reported to have pathophysiological effects in cardiovascular diseases (CVDs), and are modified by dietary fat intake, suggesting their potential as a novel biomarker. EVs were analysed by a combination of nanoparticle tracking analysis, flow cytometry, thrombin generation assay, gas chromatography, and proteomics. The first study demonstrated that EVs generated in vitro from platelets were greater in number when platelets were stimulated and had altered fatty acid compositions compared with their parent platelets, specifically a higher proportion of saturated fatty acids and a lower proportion of unsaturates, particularly arachidonic acid. The second study demonstrated a pronounced postprandial increase in the number and thrombogenicity of EVs, peaking at 4 hours after consumption of a high-fat meal, but there was no effect of replacing the fat source to include interesterified (IE) fats. The final study drew a strong association between plasma triacylglycerol (TAG) and EV numbers in patients with ischaemic heart disease (IHD), but numbers of circulating EVs were similar to those in symptomatic controls. However, the thrombogenicity of EVs from IHD patients was significantly greater. Numbers and thrombogenicity of EVs from arterial blood were similar to those from venous blood. In vitro activation of platelets, regardless of stimulation, released EVs with altered fatty acid content that do not resemble that of their parent platelets, indicating compositional remodelling during EV formation. Postprandial increases in number and thrombogenicity of EVs suggested a strong link between EVs and thrombogenicity. An increase in the thrombogenicity of EVs in IHD patients compared with symptomatic controls suggests a potentially important role for EVs in IHD.