Extracellular vesicle protein CD14 relates to common carotid intima-media thickness in eight-year-old children

Abstract

Background: Atherosclerosis is a process that begins in childhood, develops over decades and underlies the majority of cardiovascular events in adulthood. Previously, we demonstrated in adults with cardiovascular disease that levels of extracellular vesicle (EV) proteins CD14, Serpin F2 and cystatin C predict vascular outcome. Here, we study for the first time whether these EV proteins are related to vascular characteristics in healthy, young children.

Methods and results: In 141 eight-year old children of the Wheezing-Illnesses-Studie-LEidsche-Rijn birth cohort, anthropometrics and blood pressure were measured. In addition, common carotid intima-media thickness, carotid distensibility and carotid Young's elastic modulus were obtained non-invasively using ultrasound imaging. A fasting lipid spectrum was obtained and EVs were isolated from plasma. Levels of EV proteins CD14, Serpin F2 and cystatin C were measured using a multiplex assay. In a multivariable linear regression model we assessed the relation between these EV proteins and the selected vascular characteristics. Of the studied EV proteins, CD14 levels were positively related to common carotid intima-media thickness (log transformed, beta = 7.31 ln(mm)/(ng/mg) (1.24, 13.38), p = 0.02). EV proteins Serpin F2 and cystatin C were not related to common carotid intima-media thickness. In addition, we found no relation between all three EV proteins and carotid distensibility or carotid Young's elastic modulus.

Conclusion: In healthy eight-year old children, extracellular vesicle protein CD14 levels seem positively related to common carotid intima-media thickness. This would point towards inflammatory vascular alterations inflicted by extracellular vesicle protein CD14 already in early life and warrants further investigation.

Keywords: Atherosclerosis; Children; Extracellular vesicle; Inflammation; Protein; Vascular alterations.