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Article

Platelet Activation Is Triggered by Factors Secreted by Senescent Endothelial HMEC-1 Cells In Vitro

1
Center for Medical Research, University of Talca Medical School, Talca 3460000, Chile
2
Faculty of Health Sciences, University of Talca, Talca 3460000, Chile
3
Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 7500000, Chile
4
Núcleo Científico Multidisciplinario, Universidad de Talca, Talca 3460000, Chile
5
Thrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohaematology, Faculty of Health Sciences, University of Talca, Talca 3460000 Chile
6
Programa de Investigación Asociativa en Cáncer Gástrico (PIA-CG), Talca 3460000, Chile
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(9), 3287; https://doi.org/10.3390/ijms21093287
Received: 8 April 2020 / Revised: 28 April 2020 / Accepted: 1 May 2020 / Published: 6 May 2020
(This article belongs to the Special Issue Advances in Biological Functions of Platelet)
Aging is one of the main risk factors for the development of chronic diseases, with both the vascular endothelium and platelets becoming functionally altered. Cellular senescence is a form of permanent cell cycle arrest initially described in primary cells propagated in vitro, although it can also be induced by anticancer drugs and other stressful stimuli. Attesting for the complexity of the senescent phenotype, senescent cells synthesize and secrete a wide variety of bioactive molecules. This “senescence-associated secretory phenotype” (SASP) endows senescent cells with the ability to modify the tissue microenvironment in ways that may be relevant to the development of various physiological and pathological processes. So far, however, the direct role of factors secreted by senescent endothelial cells on platelet function remains unknown. In the present work, we explore the effects of SASP factors derived from senescent endothelial cells on platelet function. To this end, we took advantage of a model in which immortalized endothelial cells (HMEC-1) were induced to senesce following exposure to doxorubicin, a chemotherapeutic drug widely used in the clinic. Our results indicate that (1) low concentrations of doxorubicin induce senescence in HMEC-1 cells; (2) senescent HMEC-1 cells upregulate the expression of selected components of the SASP and (3) the media conditioned by senescent endothelial cells are capable of inducing platelet activation and aggregation. These results suggest that factors secreted by senescent endothelial cells in vivo could have a relevant role in the platelet activation observed in the elderly or in patients undergoing therapeutic stress. View Full-Text
Keywords: platelets; cellular senescence; doxorubicin; endothelial cells; SASP platelets; cellular senescence; doxorubicin; endothelial cells; SASP
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MDPI and ACS Style

Venturini, W.; Olate-Briones, A.; Valenzuela, C.; Méndez, D.; Fuentes, E.; Cayo, A.; Mancilla, D.; Segovia, R.; Brown, N.E.; Moore-Carrasco, R. Platelet Activation Is Triggered by Factors Secreted by Senescent Endothelial HMEC-1 Cells In Vitro. Int. J. Mol. Sci. 2020, 21, 3287. https://doi.org/10.3390/ijms21093287

AMA Style

Venturini W, Olate-Briones A, Valenzuela C, Méndez D, Fuentes E, Cayo A, Mancilla D, Segovia R, Brown NE, Moore-Carrasco R. Platelet Activation Is Triggered by Factors Secreted by Senescent Endothelial HMEC-1 Cells In Vitro. International Journal of Molecular Sciences. 2020; 21(9):3287. https://doi.org/10.3390/ijms21093287

Chicago/Turabian Style

Venturini, Whitney, Alexandra Olate-Briones, Claudio Valenzuela, Diego Méndez, Eduardo Fuentes, Angel Cayo, Daniel Mancilla, Raul Segovia, Nelson E. Brown, and Rodrigo Moore-Carrasco. 2020. "Platelet Activation Is Triggered by Factors Secreted by Senescent Endothelial HMEC-1 Cells In Vitro" International Journal of Molecular Sciences 21, no. 9: 3287. https://doi.org/10.3390/ijms21093287

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