Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes

Autor: Natalia Di Pietro, Marco Marchisio, Assunta Pandolfi, Feliciano Protasi, Fernanda Amicarelli, Silvano Junior Santini, Umberto Galderisi, Nadia Di Pietrantonio, Gloria Formoso, Paola Lanuti, Valeria Cordone, Laura Pietrangelo, Pamela Di Tomo, Stefano Falone, Nicola Alessio
Přispěvatelé: Di Tomo, P., Alessio, N., Falone, S., Pietrangelo, L., Lanuti, P., Cordone, V., Santini, S. J., Di Pietrantonio, N., Marchisio, M., Protasi, F., Di Pietro, N., Formoso, G., Amicarelli, F., Galderisi, U., Pandolfi, A.
Rok vydání: 2021
Předmět:
0301 basic medicine
senescence
Mitochondrion
medicine.disease_cause
Biochemistry
Umbilical cord
Antioxidants
0302 clinical medicine
Sirtuin 1
Pregnancy
Cells
Cultured
Cellular Senescence
Kinase
gestational diabete
mitochondria
Gestational diabetes
medicine.anatomical_structure
Female
Antioxidant
Human
Biotechnology
Cyclin-Dependent Kinase Inhibitor p21
Senescence
medicine.medical_specialty
endothelium
Endothelium
Human Umbilical Vein Endothelial Cell
In Vitro Techniques
Models
Biological
03 medical and health sciences
In vivo
Internal medicine
Human Umbilical Vein Endothelial Cells
Genetics
medicine
Humans
Molecular Biology
oxidative stre
In Vitro Technique
business.industry
medicine.disease
Diabetes
Gestational
Oxidative Stress
030104 developmental biology
Endocrinology
Gene Expression Regulation
Tumor Suppressor Protein p53
business
E1A-Associated p300 Protein
030217 neurology & neurosurgery
Oxidative stress
Zdroj: The FASEB Journal. 35
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.202002072rr
Popis: Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD-HUVECs) display durable pro-atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C-HUVECs (controls) exhibited oxidative stress, altered both mitochondrial membrane potential and antioxidant response, significant increase of senescent cells characterized by a reduced NAD-dependent deacetylase sirtuin-1 (SIRT1) activity together with an increase in cyclin-dependent kinase inhibitor-2A (P16), cyclin-dependent kinase inhibitor-1 (P21), and tumor protein p53 (P53) acetylation. This was associated with the p300 activation, and its silencing significantly reduced the GD-HUVECs increased protein levels of P300 and Ac-P53 thus indicating a persistent endothelial senescence via SIRT1/P300/P53/P21 pathway. Overall, our data suggest that GD-HUVECs can represent an "endothelial hyperglycemic memory" model to investigate in vitro the early endothelium senescence in cells chronically exposed to hyperglycemia in vivo.
Databáze: OpenAIRE
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