The COVID-19 pandemic worsened global food insecurity and malnutrition. Protein restriction increases the risk of poor COVID-19 outcomes and cardiovascular disease. Post-COVID-19 syndrome remains a public health concern, although its underlying mechanisms are not yet fully understood. Extracellular vesicles (EVs), released by most cell types in response to infections, have been implicated in endothelial dysfunction during the post-COVID phase. We hypothesized that EV contribute to endothelial cell (EC) dysfunction in long-term COVID-19, particularly in the setting of protein malnutrition. Circulating EVs were isolated from patients at 1 and 6 months after hospital discharge due to severe COVID-19. Endothelial relaxation was assessed in mouse aortas after a 3-month normoprotein or low-protein diet (LP). LP feeding reduced endothelium-dependent relaxation to acetylcholine, but EVs from post-COVID patients (1 and 6 months) restored endothelium-dependent relaxation. This EV effect was abolished by catalase, but not by L-NAME (a nitric oxide synthase inhibitor) or indomethacin (a cyclooxygenase inhibitor). Aortas from LP mice incubated with post-COVID EVs exhibited reduced catalase expression and increased 4-HNE adducts. In vitro amino acid restriction increased ECl death (Hoechst/Pi), and reduced NO (DAF-2DA) and H2O2 (Amplex red) levels. Incubation with post-COVID EVs for 24h increased H2O2 only in amino acid-restricted EC. EVs had no significant effect on acetylcholine-induced relaxation in normoprotein-fed mice or on EC parameters in vitro under control conditions. These findings suggest that EVs from patients 1 and 6 months after severe COVID-19 impact aortic endothelial function by increasing H₂O₂ contribution under conditions of malnutrition.
Bobato et al. (Fri,) studied this question.