Extracellular vesicle cargo can differ by race and sex and is associated with mortality risk factors

Differential mortality rates remain a significant health disparity in the United States, suggesting the need to investigate novel potential molecular markers associated with mortality. Extracellular vesicles (EVs), including exosomes, microvesicles and apoptotic bodies, are lipid-bound vesicles secreted by cells into the circulation. EVs mediate intercellular communication by shuttling functional signaling molecules as cargo. EV characteristics by race in the context of mortality risk factors have not been described.

Researchers at the National Institute on Aging isolated plasma EVs from a cross-sectional cohort of African Americans (AA) and whites and found no significant differences in EV size, distribution or concentration between race or by sex. However, EV cargo showed increased levels of phospho-p53, total p53, cleaved caspase 3, ERK1/2 and phospho-AKT in white individuals compared to AAs. phospho-IGF-1R levels were significantly higher in females compared to males. EV concentration was significantly associated with several clinical mortality risk factors: high-sensitivity C-reactive protein (hsCRP), homeostatic model assessment of insulin resistance (HOMA-IR), alkaline phosphatase, body mass index, waist circumference and pulse pressure. The association of EV proteins with mortality markers were dependent on race. These data suggest that EV cargo can differ by race and sex and is associated with mortality risk factors.

EV characteristics across different demographics

(A) Two EV-depleted samples as negative controls, cell lysate, and plasma EV samples were lysed with MPER, analyzed by SDS-PAGE and probed for the known EV markers CD9 and Flotillin1 (Flot1) and the purity markers GM130 and Apolipoprotein A1 (ApoA1). Full immunoblots are in Supp. Fig. 2. (B) Electron microscopy images of plasma EVs scale bar = 200 nm. (C) EV size distribution, (D) concentration, (E) size mean, and (F) size mode were analyzed across each demographic using Nanoparticle Tracking Analysis (NTA). Two-way ANOVAs tested the association of sex and race with EV size mean, size mode or concentration. Lines indicate the mean and bars indicate the standard error of the mean. AA, African American; W, white.