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-Fernández, Concepción, Rossello, Xavier, Lavandero, Sergio, Yellon, Derek M, Davidson, Sean M
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/18007
Acceso en línea:http://hdl.handle.net/20.500.12105/18007
Access Level:acceso abierto
Palabra clave:Endothelium
Exosomes
Extracellular vesicles
Senescence
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
Biomarkers
Cellular Senescence
Endothelial Cells
Extracellular Vesicles
Flow Cytometry
Human Umbilical Vein Endothelial Cells
Humans
Tetraspanin 29
Tetraspanin 30
beta-Galactosidase
rab GTP-Binding Proteins
rab7 GTP-Binding Proteins
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 β-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, nanoparticle 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.