Extracellular vesicles from post-COVID-19 patients alter endothelial function under protein restriction

Area of Science:

• Cardiovascular Biology
• Infectious Disease Immunology
• Nutritional Science

Background:

• The COVID-19 pandemic exacerbated global food insecurity and malnutrition.
• Protein restriction is linked to adverse COVID-19 outcomes and cardiovascular disease.
• Post-COVID-19 syndrome involves endothelial dysfunction, potentially mediated by extracellular vesicles (EVs).

Purpose of the Study:

• To investigate the role of extracellular vesicles (EVs) in endothelial cell (EC) dysfunction in long-term COVID-19, especially with protein malnutrition.
• To determine if EVs from post-COVID-19 patients affect aortic endothelial function under malnourished conditions.

Main Methods:

• Isolated circulating EVs from patients 1 and 6 months post-hospital discharge for severe COVID-19.
• Assessed endothelial relaxation in mouse aortas after 3 months on normoprotein or low-protein diets (LP).
• Evaluated EC death, nitric oxide (NO), and hydrogen peroxide (H2O2) levels in vitro under amino acid restriction.

Main Results:

• Low-protein diet impaired endothelium-dependent relaxation, which was restored by post-COVID EVs.
• This EV effect was dependent on catalase activity and linked to reduced catalase and increased 4-HNE adducts in LP mouse aortas.
• In vitro, post-COVID EVs increased H2O2 in amino acid-restricted ECs, but not under normal conditions.

Conclusions:

• EVs from patients 1-6 months after severe COVID-19 can impair aortic endothelial function.
• This impairment is exacerbated by malnutrition and involves increased hydrogen peroxide (H2O2) contribution.
• These findings suggest a mechanism linking post-COVID-19 endothelial dysfunction to malnutrition.