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

• Main Authors: Whitney Venturini, Alexandra Olate-Briones, Claudio Valenzuela, Diego Méndez, Eduardo Fuentes, Angel Cayo, Daniel Mancilla, Raul Segovia, Nelson E. Brown, Rodrigo Moore-Carrasco
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: International Journal of Molecular Sciences
• Subjects: platelets; cellular senescence; doxorubicin; endothelial cells; SASP
• Online Access: https://www.mdpi.com/1422-0067/21/9/3287

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.