Low fluid shear stress stimulates the uptake of noxious endothelial extracellular vesicles via MCAM and PECAM-1 cell adhesion molecules.


Journal

Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479

Informations de publication

Date de publication:
Oct 2024
Historique:
received: 13 06 2023
accepted: 19 01 2024
medline: 14 10 2024
pubmed: 14 10 2024
entrez: 14 10 2024
Statut: ppublish

Résumé

Atherosclerotic lesions mainly form in arterial areas exposed to low shear stress (LSS), where endothelial cells express a senescent and inflammatory phenotype. Conversely, areas exposed to high shear stress (HSS) are protected from plaque development. Endothelial extracellular vesicles (EVs) have been shown to regulate inflammation and senescence, and therefore play a crucial role in vascular homeostasis. Whilst previous studies have shown links between hemodynamic forces and EV release, the effects of shear stress on the release and uptake of endothelial EVs remains elusive. We aim to decipher the interplay between these processes in endothelial cells exposed to atheroprone or atheroprotective shear stress. Confluent HUVECs were exposed to LSS or HSS for 24 h. Large and small EVs were isolated from conditioned medium by centrifugation and size exclusion chromatography. They were characterised by TEM, Western blot, tunable resistive pulse sensing, flow cytometry and proteomics. Uptake experiments were performed using fluorescently-labelled EVs and differences between groups were assessed by flow cytometry and confocal microscopy. We found that levels of large and small EVs in conditioned media were fifty and five times higher in HSS than in LSS conditions, respectively. In vivo and in vitro uptake experiments revealed greater EV incorporation by cells exposed to LSS conditions. Additionally, endothelial LSS-EVs have a greater affinity for HUVECs than HSS-EVs or EVs derived from platelets, erythrocytes and leukocytes. Proteomic analysis revealed that LSS-EVs were enriched in adhesion proteins (PECAM1, MCAM), participating in EV uptake by endothelial cells. LSS-EVs also carried mitochondrial material, which may be implicated in elevating ROS levels in recipient cells. These findings suggest that shear stress influences EV biogenesis and uptake. Given the major role of EVs and shear stress in vascular health, deciphering the relation between these processes may yield innovative strategies for the early detection and treatment of endothelial dysfunction.

Identifiants

pubmed: 39400522
doi: 10.1002/jev2.12414
doi:

Substances chimiques

Platelet Endothelial Cell Adhesion Molecule-1 0
PECAM1 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e12414

Subventions

Organisme : Fondation pour la Recherche Médicale
ID : EQU202003010767
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 665850
Organisme : Institut National Du Cancer
ID : INCA-PLBIO19-059
Organisme : Agence Nationale de la Recherche
ID : ANR-16-CE14-0015-01
Organisme : Agence Nationale de la Recherche
ID : ANR-16-CE92-0032-02
Organisme : Agence Nationale de la Recherche
ID : ANR-20-CE18-0026-01

Informations de copyright

© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.

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Auteurs

Pierre-Michaël Coly (PM)

Université Paris-Cité, PARCC, INSERM, Paris, France.
Institute of Psychiatry and Neuroscience of Paris (IPNP), Université de Paris, INSERM, Paris, France.

Shruti Chatterjee (S)

Université Paris-Cité, PARCC, INSERM, Paris, France.

Fariza Mezine (F)

Université Paris-Cité, PARCC, INSERM, Paris, France.

Christelle El Jekmek (CE)

Université Paris-Cité, PARCC, INSERM, Paris, France.

Cécile Devue (C)

Université Paris-Cité, PARCC, INSERM, Paris, France.

Thomas Nipoti (T)

Université Paris-Cité, PARCC, INSERM, Paris, France.

Stephane Mazlan (S)

Université Paris-Cité, PARCC, INSERM, Paris, France.

Maribel Lara Corona (ML)

Institute of Psychiatry and Neuroscience of Paris (IPNP), Université de Paris, INSERM, Paris, France.

Florent Dingli (F)

Institut Curie, PSL Research University, Centre de Recherche, CurieCoreTech Spectrométrie de Masse Protéomique, Paris, France.

Damarys Loew (D)

Institut Curie, PSL Research University, Centre de Recherche, CurieCoreTech Spectrométrie de Masse Protéomique, Paris, France.

Guillaume van Niel (G)

Institute of Psychiatry and Neuroscience of Paris (IPNP), Université de Paris, INSERM, Paris, France.
GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte Anne, Paris, France.

Xavier Loyer (X)

Université Paris-Cité, PARCC, INSERM, Paris, France.

Chantal M Boulanger (CM)

Université Paris-Cité, PARCC, INSERM, Paris, France.

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