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LPS-enriched small extracellular vesicles from metabolic syndrome patients trigger endothelial dysfunction by activation of TLR4
- Source :
- Metabolism, Metabolism, Elsevier, 2021, 118, pp.154727. ⟨10.1016/j.metabol.2021.154727⟩, Metabolism, 2021, 118, pp.154727. ⟨10.1016/j.metabol.2021.154727⟩
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- Background Metabolic syndrome (MetS) is characterized by a cluster of interconnected risk factors -hyperglycemia, dyslipidemia, hypertension and obesity- leading to an increased risk of cardiovascular events. Small extracellular vesicles (sEVs) can be considered as new biomarkers of different pathologies, and they are involved in intercellular communication. Here, we hypothesize that sEVs are implicated in MetS-associated endothelial dysfunction. Methods Circulating sEVs of non-MetS (nMetS) subjects and MetS patients were isolated from plasma and characterized. Thereafter, sEV effects on endothelial function were analyzed by measuring nitric oxide (NO) and reactive oxygen species (ROS) production, and mitochondrial dynamic proteins on human endothelial aortic cells (HAoECs). Results Circulating levels of sEVs positively correlated with anthropometric and biochemical parameters including visceral obesity, glycaemia, insulinemia, and dyslipidemia. Treatment of HAoECs with sEVs from MetS patients decreased NO production through the inhibition of the endothelial NO-synthase activity. Injection of MetS-sEVs into mice impaired endothelium-dependent relaxation induced by acetylcholine. Furthermore, MetS-sEVs increased DHE and MitoSox-associated fluorescence in HAoECs, reflecting enhanced cytosolic and mitochondrial ROS production which was not associated with mitochondrial biogenesis or dynamic changes. MetS patients displayed elevated circulating levels of LPS in plasma, and, at least in part, it was associated to circulating sEVs. Pharmacological inhibition and down-regulation of TLR4, as well as sEV-carried LPS neutralization, results in a substantial decrease of ROS production induced by MetS-sEVs. Conclusion These results evidence sEVs from MetS patients as potential new biomarkers for this syndrome, and TLR4 pathway activation by sEVs provides a link between the endothelial dysfunction and metabolic disturbances described in MetS.
- Subjects :
- Lipopolysaccharides
Male
0301 basic medicine
Mitochondrial ROS
Endocrinology, Diabetes and Metabolism
viruses
[SDV]Life Sciences [q-bio]
030204 cardiovascular system & hematology
Exosomes
Cohort Studies
Mice
chemistry.chemical_compound
Cytosol
Endocrinology
0302 clinical medicine
Medicine
030212 general & internal medicine
Endothelial dysfunction
Cells, Cultured
chemistry.chemical_classification
Organelle Biogenesis
virus diseases
MESH: Toll-Like Receptor 4
Middle Aged
respiratory system
Metabolic syndrome
Mitochondria
[SDV] Life Sciences [q-bio]
Female
MESH: Endothelium, Vascular
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
MESH: Metabolic Syndrome
030209 endocrinology & metabolism
Nitric Oxide
Nitric oxide
Extracellular Vesicles
03 medical and health sciences
Insulin resistance
Internal medicine
Animals
Humans
MESH: Extracellular Vesicles
Reactive oxygen species
business.industry
medicine.disease
Toll-Like Receptor 4
Oxidative Stress
030104 developmental biology
chemistry
Mitochondrial biogenesis
TLR4
Endothelium, Vascular
MESH: Lipopolysaccharides
Reactive Oxygen Species
business
Dyslipidemia
Subjects
Details
- Language :
- English
- ISSN :
- 00260495
- Database :
- OpenAIRE
- Journal :
- Metabolism, Metabolism, Elsevier, 2021, 118, pp.154727. ⟨10.1016/j.metabol.2021.154727⟩, Metabolism, 2021, 118, pp.154727. ⟨10.1016/j.metabol.2021.154727⟩
- Accession number :
- edsair.doi.dedup.....2664bef9bc6295907d692dda54fb0307