Abstract Extracellular vesicles (EV) are an emerging biomarker source for diagnosis and prognosis of cardiovascular disease. A protein comparison of plasma EVs in relation to blood plasma and atherosclerotic plaque has not been performed but would provide insight into the origin and content of biomarker sources, and their association with atherosclerotic progression. Using samples of 88 carotid endarterectomy patients in the Athero-Express, 92 proteins (Olink Cardiovascular III panel) were measured in citrate plasma, plasma derived LDL-EVs and atherosclerotic plaque. Proteins were correlated between sources and were related to occurrence of pre-operative stroke and three-year major adverse cardiovascular events (MACE). Plasma and EV proteins correlated moderately on average, but with substantial variability. Plasma and EVs showed little correlation with plaque, suggesting that these circulating biomarkers may not originate from the latter. Plaque (n = 17) contained most differentially-expressed proteins in patients with stroke, opposed to EVs (n = 6) and plasma (n = 5). In contrast, EVs contained most differentially-expressed proteins for MACE (n = 21) compared to plasma (n = 9) and plaque (n = 1). EVs appear to provide additional information about severity and progression of systemic atherosclerosis than can be obtained from plasma or atherosclerotic plaque.

Ethical approval for this study (TME/C-01.18) was provided by the Medical Research Ethics Committee of University Medical Center Utrecht, Utrecht, The Netherlands on 10 April 2002, and all research was conducted according to the principles of the Declaration of Helsinki (59th amendment, Seoul 2008) and in accordance with the Dutch Medical Research Involving Human Subjects Act (WMO).

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