Oxidized High-Density Lipoprotein Induces Endothelial Fibrosis Promoting Hyperpermeability, Hypotension, and Increased Mortality
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Archivos
Fecha
2022
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
Antioxidants
Nombre de Curso
Licencia CC
Atribución 4.0 Internacional (CC BY 4.0)
Licencia CC
https://creativecommons.org/licenses/by/4.0/
Resumen
During systemic inflammation, reactive oxygen species (ROS) are generated in the blood-stream, producing large amounts of oxidized HDL (oxHDL). OxHDL loses the vascular protective
features of native HDL, acquiring detrimental actions. Systemic inflammation promotes endothelial
fibrosis, characterized by adhesion protein downregulation and fibrotic-specific gene upregulation,
disrupting endothelial monolayer integrity. Severe systemic inflammatory conditions, as found in
critically ill patients in the intensive care unit (ICU), exhibit endothelial hyperpermeability, hypoten sion, and organ hypoperfusion, promoting organ dysfunction and increased mortality. Because
endothelial fibrosis disturbs the endothelium, it is proposed that it is the cellular and molecular
origin of endothelial hyperpermeability and the subsequent deleterious consequences. However,
whether oxHDL is involved in this process is unknown. The aim of this study was to investigate
the fibrotic effect of oxHDL on the endothelium, to elucidate the underlying molecular and cellular
mechanism, and to determine its effects on vascular permeability, blood pressure, and mortality. The
results showed that oxHDL induces endothelial fibrosis through the LOX-1/NOX-2/ROS/NF-κB
pathway, TGF-β secretion, and ALK-5/Smad activation. OxHDL-treated rats showed endothelial
hyperpermeability, hypotension, and an enhanced risk of death and mortality, which was prevented
using an ALK-5 inhibitor and antioxidant diet consumption. Additionally, the ICU patients showed
fibrotic endothelial cells, and the resuscitation fluid volume administered correlated with the plasma
oxHDL levels associated with an elevated risk of death and mortality. We conclude that oxHDL
generates endothelial fibrosis, impacting blood pressure regulation and survival.
Notas
Indexación: Scopus
Palabras clave
oxHDL, oxidative stress, endothelium, fibrosis, blood pressure, mortality, hyperpermeability
Citación
DOI
https://doi.org/10.3390/antiox11122469