Linking in vitro models of endothelial dysfunction with cell senescence

Francisco R. Jimenez Trinidad, Marta Arrieta Ruiz, Núria Solanes Batlló, Àngela Vea Badenes, Joaquim Bobi Gibert, Antoni Valera Cañellas, Mercè Roqué Moreno, Xavier Freixa Rofastes, Manel Sabaté Tenas, Ana Paula Dantas, Olga Tura‐ceide, Montserrat Rigol Muxart*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
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Abstract

Endothelial cell dysfunction is the principal cause of several cardiovascular diseases that are increasing in prevalence, healthcare costs, and mortality. Developing a standardized, representative in vitro model of endothelial cell dysfunction is fundamental to a greater understanding of the pathophysiology, and to aiding the development of novel pharmacological therapies. We subjected human umbilical vein endothelial cells (HUVECs) to different periods of nutrient deprivation or increasing doses of H2O2 to represent starvation or elevated oxidative stress, respectively, to investigate changes in cellular function. Both in vitro cellular models of endothelial cell dysfunction‐associated senescence developed in this study, starvation and oxidative stress, were validated by markers of cellular senescence (increase in β‐galactosidase activity, and changes in senescence gene markers SIRT1 and P21) and endothelial dysfunction as denoted by reductions in angiogenic and migratory capabilities. HUVECs showed a significant H2O2 concentration-dependent reduction in cell viability (p<0.0001), and a significant increase in oxidative stress (p<0.0001). Furthermore, HUVECs subjected to 96h of starvation, or exposed to concentrations of H2O2 of 400 to 1000μM resulted in impaired angiogenic and migratory potentials. These models will enable improved physiological studies of endothelial cell dysfunction, and the rapid testing of cellular efficacy and toxicity of future novel therapeutic compounds.

Original languageEnglish
Article number1323
JournalLife
Volume11
Issue number12
DOIs
Publication statusPublished - 30 Nov 2021

Bibliographical note

Funding Information:
Funding: This research was funded by Beca de Investigacion Basica en Cardiologia from the Sociedad Española de Cardiologia, Fondo de Investigacion en Salud (grants PI18/00277, PI16/00742, PI19/00264, PI18/00960 and PI15/00553) from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III–Fondo Europeo de Desarrollo Regional (FEDER), and Spanish Society of Respiratory Medicine (SEPAR) and Catalan Society of Pneumology (SOCAP) grants. FRJT and OTC are the recipients of the Ayudas para la formación de profesorado universitario (FPU19/04925) and Miguel Servet (CP17/00114) grants, respectively, from the Spanish Ministry of Science and Innovation. IDIBAPS belongs to the CERCA Programme, and receives partial funding from the Generalitat de Catalunya. Cofunding was provided by the Fondo Europeo de Desarrollo Regional (FEDER); “Una manera de hacer Europa”.

Funding Information:
This research was funded by Beca de Investigacion Basica en Cardiologia from the Sociedad Espa?ola de Cardiologia, Fondo de Investigacion en Salud (grants PI18/00277, PI16/00742, PI19/00264, PI18/00960 and PI15/00553) from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III?Fondo Europeo de Desarrollo Regional (FEDER), and Spanish Society of Respiratory Medicine (SEPAR) and Catalan Society of Pneumology (SOCAP) grants. FRJT and OTC are the recipients of the Ayudas para la formaci?n de profesorado universitario (FPU19/04925) and Miguel Servet (CP17/00114) grants, respectively, from the Spanish Ministry of Science and Innovation. IDIBAPS belongs to the CERCA Programme, and receives partial funding from the Generalitat de Catalunya. Cofunding was provided by the Fondo Europeo de Desarrollo Regional (FEDER); ?Una manera de hacer Europa?.

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© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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