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

Abstract

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.

The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol

“…The reading was performed on a BD FacsLyric flow cytometer (BD Biosciences, San José, CA, USA). CD61 FITC was used to identify the platelet population [ 58 , 60 ].…”

Nutrition Interventions of Herbal Compounds on Cellular Senescence

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Beyond Static Pipes: Mechanisms and In Vitro Models of Vascular Aging

“…Low concentrations of the chemotherapeutic drug doxorubicin were shown to induce senescence of immortalized VECs, which then expressed typical components of the SASP. Interestingly, treatment with SASP-containing conditioned medium induced platelet activation and aggregation (Venturini et al 2020). It is important to highlight that senescent cells or their products can be in principle cleared, as demonstrated in animal models through different methods (e.g., genetic clearing using the INK-ATTAC model, treatment with dasatinib and quercetin, treatment with the Janus kinase (JAK1/2) inhibitor ruxolitinib) (Xu et al 2015(Xu et al , 2018.…”