Plasma extracellular vesicle-associated inflammatory proteins are promising potential clinical biomarkers of mortality

Even before the COVID-19 pandemic declines in life expectancy in the United States were attributed to increased mortality rates in midlife adults across racial and ethnic groups, indicating a need for markers to identify individuals at risk for early mortality. Extracellular vesicles (EVs) are small, lipid-bound vesicles capable of shuttling functional proteins, nucleic acids, and lipids. Given their role as intercellular communicators and potential biomarkers of disease, researchers at the National Institute on Aging explored whether circulating EVs may be markers of mortality in a prospective, racially, and socioeconomically diverse middle-aged cohort. They isolated plasma EVs from 76 individuals (mean age = 59.6 years) who died within a 5 year period and 76 surviving individuals matched by age, race, and poverty status. There were no significant differences in EV concentration, size, or EV-associated mitochondrial DNA levels associated with mortality. The researchers found that several EV-associated inflammatory proteins including CCL23, CSF-1, CXCL9, GDNF, MCP-1, STAMBP, and 4E-BP1 were significantly associated with mortality. IL-10RB and CDCP1 were more likely to be present in plasma EVs from deceased individuals than in their alive counterparts. They also report differences in EV-associated inflammatory proteins with poverty status, race, and sex. These results suggest that plasma EV-associated inflammatory proteins are promising potential clinical biomarkers of mortality.

Significant association of EV inflammatory protein levels with mortality

Figure 3

Plasma EVs were isolated from 76 individuals deceased within 5 years along with 76 surviving individuals. EVs were lysed and analyzed using a proximity extension assay. Normalized protein levels (NPL) are shown. Linear regression was used to determine the relationships between protein levels and later mortality status accounting for sex, race, and poverty status.

Noren Hooten N, Torres S, Mode NA, Zonderman AB, Ghosh P, Ezike N, Evans MK. (2022) Association of extracellular vesicle inflammatory proteins and mortality. Sci Rep 12(1):14049. [article]

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