Browsing by Author "Moore-Carrasco, Rodrigo"

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    Platelet Activation Is Triggered by Factors Secreted by Senescent Endothelial HMEC-1 Cells In Vitro
    (2020) Venturini, Whitney; Olate-Briones, Alexandra; Valenzuela, Claudio; Mendez, Diego; Fuentes, Eduardo; Cayo, Angel; Mancilla, Daniel; Segovia, Raul; Brown, Nelson E.; Moore-Carrasco, Rodrigo
    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.
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    Shortcomings, limitations and gaps in physiological roles of extracellular vesicles in obesity
    (2024) Valero, Paola; Silva, Katherin; Valenzuela-Hinrichsen, Andres; Vasquez, Antonia; Espinoza, Fernanda; Lira, Fernanda; Cornejo, Marcelo; Fuentes, Gonzalo; Gonzalez, Daniel; Moore-Carrasco, Rodrigo; van der Beek, Eline M.; Hillebrands, Jan-Luuk; van Goor, Harry; Grismaldo, Adriana; Sobrevia, Luis
    Extracellular vesicles (EVs) play a crucial role in mediating communication between cells across species and kingdoms. The intercellular communication facilitated by EVs through autocrine and paracrine signalling mechanisms is essential for cell survival, maintaining normal metabolic functions and ensuring overall bodily homeostasis and health. Extracellular vesicles are present in various bodily fluids, such as pleural effusions, plasma, breast milk, amniotic fluid, semen and saliva. Additionally, the generation and release of EVs contribute to the removal of cellular waste. Patients with obesity exhibit a higher release and amount of circulating EVs than individuals with normal weight. This increased EV release in obesity might contribute to the inflammatory state characteristic of this metabolic condition, because higher levels of pro-inflammatory molecules are found within their cargo. However, interpreting results related to EV abundance, cargo and biological actions can be complicated by several factors; these include variations in cell sources, a wide age range (from children to the elderly), a mix of females and males, medication use and health status, a range of body weights (from normal weight to morbid obesity) and differences between in vitro assays using cell lines versus primary cultures. This article addresses the shortcomings, limitations and gaps in knowledge, providing a framework for enhancing our understanding of the physiological effects of EVs on obesity. image