Inflammatory Stroke Extracellular Vesicles Induce Macrophage Activation

: Couch Y, Akbar N, Davis S, Fischer R, Dickens AM, Neuhaus AA, Burgess AI, Rothwell PM, Buchan AM

Publisher: LIPPINCOTT WILLIAMS & WILKINS

: 2017

: Stroke

: STROKE

: 48

: 8

: 2292

: 2296

: 8

: 0039-2499

DOI: https://doi.org/10.1161/STROKEAHA.117.017236

Background and Purpose-Extracellular vesicles (EVs) are protein-lipid complexes released from cells, as well as actively exocytosed, as part of normal physiology, but also during pathological processes such as those occurring during a stroke. Our aim was to determine the inflammatory potential of stroke EVs.Methods-EVs were quantified and analyzed in the sera of patients after an acute stroke (< 24 hours; OXVASC [Oxford Vascular Study]). Isolated EV fractions were subjected to untargeted proteomic analysis by liquid chromatography massspectrometry/mass-spectrometry and then applied to macrophages in culture to investigate inflammatory gene expression.Results-EV number, but not size, is significantly increased in stroke patients when compared to age-matched controls. Proteomic analysis reveals an overall increase in acute phase proteins, including C-reactive protein. EV fractions applied to monocyte-differentiated macrophage cultures induced inflammatory gene expression.Conclusions-Together these data show that EVs from stroke patients are proinflammatory in nature and are capable of inducing inflammation in immune cells.