PCSK9 as a mediator of monocytes transendothelial activation in obstructive sleep apnoea: A translational study
Abstract
Obstructive sleep apnoea (OSA) causes intermittent hypoxia (IH) during sleep which is the main trigger for associated cardiovascular complications. IH increases endothelial permeability and vascular remodelling. The proprotein convertase subtilisine kexine type 9 (PCSK9) is capable of promoting vascular inflammation. This study aims at characterizing PCSK9 expression in OSA patients and cellular models exposed to IH for unravelling PCSK9 role in monocytes migration and endothelial permeability. PCSK9 levels were evaluated by ELISA in serum from 48 OSA patients without comorbidities and 27 control subjects, before and after 6 months of treatment by Continuous Positive Airway Pressure (CPAP). Human Aortic Endothelial Cells and THP-1 monocytes were exposed to IH in vitro. Monocyte migration was studied after IH or OSA patients' sera exposure, treated or not with inhibitors of PCSK9 (SBC-115076 or anti-PCSK9 mAb1), and endothelial permeability was evaluated by dextran-FITC passage. PCSK9 was elevated in OSA patients compared to control subjects and this difference was abolished after 6 months of CPAP treatment. In multivariate analysis, the presence of OSA was independently associated with an increased level of PCSK9 at baseline. Exposure to IH increased endothelial permeability, and both IH and OSA patient's sera increased THP-1 migration. IH upregulated ICAM1, CD163 and SOD2 gene and SOD2 protein expression in THP-1 cells. All these effects were reversed by PCSK9 inhibition. OSA is one of the determinants of increased PCSK9 in humans. PCSK9 inhibition reverses IH-induced endothelial permeability and monocyte migration, suggesting that PCSK9 could be a key player in IH-induced vascular remodelling.
Related
- CB2 activation during epileptogenesis recruits immunomodulatory monocytes and mitigates cognitive, affective and seizure outcomes
- Translational activation: An unforeseen function of RNP biomolecular condensates
- Chemical proteomics reveals post-translational remodeling of endosomal pathways during macrophage activation.
- The Alzheimer's Disease-associated gene CD2AP regulates permeability of endothelial cells and transendothelial migration of immune cells
- Bringing translational structure to complex immune-mediated conditions: the ACT (Activation–Constraint–Tissue Context) framework for divergent phenotypes
BibTeX
@article{reveyaz2026pcsk9,
title = {{PCSK9 as a mediator of monocytes transendothelial activation in obstructive sleep apnoea: A translational study}},
author = {Marc-Adrien Reveyaz and Yann Sibaud and Maël Brossette and Alejandro Arco-Hierves and Antoine Boutin and Emeline Lemarié and Jonathan Gaucher and Van Ngo and Marie Joyeux-Faure and Sébastien Bailly and Renaud Tamisier and Jean-Louis Pépin and Gilles Faury and Anne Briançon-Marjollet},
journal = {Biochimica et Biophysica Acta - Molecular Basis of Disease},
year = {2026},
month = nov,
doi = {10.1016/j.bbadis.2026.168436},
url = {https://inserm.hal.science/inserm-05849470v1},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - JOUR
TI - PCSK9 as a mediator of monocytes transendothelial activation in obstructive sleep apnoea: A translational study
AU - Marc-Adrien Reveyaz
AU - Yann Sibaud
AU - Maël Brossette
AU - Alejandro Arco-Hierves
AU - Antoine Boutin
AU - Emeline Lemarié
AU - Jonathan Gaucher
AU - Van Ngo
AU - Marie Joyeux-Faure
AU - Sébastien Bailly
AU - Renaud Tamisier
AU - Jean-Louis Pépin
AU - Gilles Faury
AU - Anne Briançon-Marjollet
PY - 2026
DA - 2026/11/03
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
DO - 10.1016/j.bbadis.2026.168436
UR - https://inserm.hal.science/inserm-05849470v1
AB - Obstructive sleep apnoea (OSA) causes intermittent hypoxia (IH) during sleep which is the main trigger for associated cardiovascular complications. IH increases endothelial permeability and vascular remodelling. The proprotein convertase subtilisine kexine type 9 (PCSK9) is capable of promoting vascular inflammation. This study aims at characterizing PCSK9 expression in OSA patients and cellular models exposed to IH for unravelling PCSK9 role in monocytes migration and endothelial permeability. PCSK9 levels were evaluated by ELISA in serum from 48 OSA patients without comorbidities and 27 control subjects, before and after 6 months of treatment by Continuous Positive Airway Pressure (CPAP). Human Aortic Endothelial Cells and THP-1 monocytes were exposed to IH in vitro. Monocyte migration was studied after IH or OSA patients' sera exposure, treated or not with inhibitors of PCSK9 (SBC-115076 or anti-PCSK9 mAb1), and endothelial permeability was evaluated by dextran-FITC passage. PCSK9 was elevated in OSA patients compared to control subjects and this difference was abolished after 6 months of CPAP treatment. In multivariate analysis, the presence of OSA was independently associated with an increased level of PCSK9 at baseline. Exposure to IH increased endothelial permeability, and both IH and OSA patient's sera increased THP-1 migration. IH upregulated ICAM1, CD163 and SOD2 gene and SOD2 protein expression in THP-1 cells. All these effects were reversed by PCSK9 inhibition. OSA is one of the determinants of increased PCSK9 in humans. PCSK9 inhibition reverses IH-induced endothelial permeability and monocyte migration, suggesting that PCSK9 could be a key player in IH-induced vascular remodelling.
SN - 0925-4439
ER -