Increased production of functional small extracellular vesicles in senescent endothelial cells

Small extracellular vesicles (EVs) are novel players in vascular biology. However, a thorough understanding of their production and function remains elusive. Endothelial senescence is a key feature of vascular ageing and thus, is an attractive therapeutic target for the treatment of vascular disease...

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Detalles Bibliográficos
Autores: Riquelme, Jaime A., Takov, Kaloyan, Santiago-Fernandez, Concepcion, Rosselló, Xavier, Lavandero, Sergio, Yellon, Derek M., Davidson, Sean M.
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/19647
Acceso en línea:https://hdl.handle.net/20.500.13003/19647
Access Level:acceso abierto
Palabra clave:Exosomes
Tetraspanin 29
Biomarkers
Human Umbilical Vein Endothelial Cells
rab GTP-Binding Proteins
Cellular Senescence
beta-Galactosidase
Extracellular Vesicles
Flow Cytometry
Humans
Endothelial Cells
Tetraspanin 30
Citometría de Flujo
Humanos
Biomarcadores
Senescencia Celular
Vesículas Extracelulares
Células Endoteliales de la Vena Umbilical Humana
Tetraspanina 29
Tetraspanina 30
beta-Galactosidasa
Exosomas
Células Endoteliales
Proteínas de Unión al GTP rab
endothelium
exosomes
extracellular vesicles
senescence
Descripción
Sumario:Small extracellular vesicles (EVs) are novel players in vascular biology. However, a thorough understanding of their production and function remains elusive. Endothelial senescence is a key feature of vascular ageing and thus, is an attractive therapeutic target for the treatment of vascular disease. In this study, we sought to characterize the EV production of senescent endothelial cells. To achieve this, Human Umbilical Vascular Endothelial Cells (HUVECs) were replicated until they reached senescence, as determined by measurement of Senescence-Associated beta-Galactosidase activity via microscopy and flow cytometry. Expression of the endosomal marker Rab7 and the EV marker CD63 was determined by immunofluorescence. Small EVs were isolated by ultracentrifugation and characterized using electron microscopy, nanopresearch article tracking analysis and immunoassays to assess morphology, size, concentration and expression of exosome markers CD9 and CD81. Migration of HUVECs in response to EVs was studied using a transwell assay. The results showed that senescent endothelial cells express higher levels of Rab7 and CD63. Moreover, senescent endothelial cells produced higher levels of CD9- and CD81-positive EVs. Additionally, small EVs from both young and senescent endothelial cells promoted HUVEC migration. Overall, senescent endothelial cells produce an increased number of functional small EVs, which may have a role in vascular physiology and disease.