Extracellular Vesicles (EVs) Derived from Senescent Endothelial Cells Promote Platelet Activation
Year: 2026
Type: article
Abstract: Thrombotic cardiovascular diseases are frequent side effects of cancer therapy with cytotoxic drugs such as Doxorubicin. Endothelial cell senescence is emerging as a critical mechanism underlying endothelial dysfunction in this context. Senescent cells, although unable to proliferate, secrete bioactive molecules that alter the tissue microenvironment, a feature known as the senescence-associated secretory phenotype (SASP). Besides soluble molecules, senescent cells also release extracellular vesicles (EVs). Previous studies indicate that senescent endothelial cells produce a secretome that promotes platelet activation; however, the contribution of EVs remains unclear. Here, we show that human microvascular endothelial cells (HMEC-1) exposed to Doxorubicin undergo senescence, display endothelial dysfunction, and release EVs. We found no differences in the concentration or size distribution of EVs from senescent and non-senescent cells. Nevertheless, EVs from senescent HMEC-1 promoted platelet activation more strongly than EVs from control cells. Notably, EVs alone did not induce platelet aggregation, suggesting that soluble factors are also required to support platelet-dependent hemostasis. These findings reveal that EVs from senescent endothelial cells contribute to platelet activation, a process that may favor thrombosis in patients receiving Doxorubicin-based chemotherapy.
DOI: 10.3390/ijms27020869
Authors: Whitney Venturini, Angel Cayo, Gabriel Diaz-Serrano, Sofia Sanhueza, Ricardo Huilcaman, Diego Méndez, Danitza Rebolledo-Mira, Catalina Silva-Pereira, Francisca Torres-Orellana, Felipe Troncoso, Carlos Escudero, Eduardo Fuentes, Andrew F. G. Quest, Claudio Valenzuela, Juan C. Tapia Amaro, Nelson E. Brown, Rodrigo Moore-Carrasco
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: CO-CRYSTALS OF CARBOXYLIC ACID DERIVATIVES AND HCN CHANNEL BLOCKERS: AN ALTERNATIVE APPROACH TO IMPROVE CANCER THERAPY BY BLOCKING HCN CHANNELS, G1713336366, ORGANIZATION OF AN ADULT PARASYMPATHETIC NEURAL NETWORK, G551219040, G5678257495, CENTRO AVANZADO DE ENFERMEDADES CRONICAS/ ADVANCED CENTER FOR CHRONIC DISEASES (ACCDIS), THERAPEUTIC HYPOTHERMIA REDUCES HYPOXIA-MEDIATED BRAIN INJURY IN MALE OFFSPRING FROM EXPERIMENTAL PREECLAMPSIA. ROLE OF BRAIN VASCULAR RESPONSE AND ENDOTHELIAL VEGF/VEGFR2/NO SIGNALING PATHWAY., CAVEOLIN-1-INDUCED CHANGES IN CANCER CELL METABOLISM AND EXOSOME COMPOSITION AS MEDIATORS OF M2 MACROPHAGE POLARIZATION TO PROMOTE TUMOR ANGIOGENESIS, CENTRO DE ESTUDIOS AVANZADOS DE ENFERMEDADES CRONICAS (ACCDIS), PHOSPHATASES AND EXOSOMES IN CAVEOLIN-1-MEDIATED METASTASIS, THE ROLE OF ADIPOCYTE DERIVED EXTRACELLULAR VESICLES CONTAINING CAVEOLIN-1 IN PROMOTING TUMOR ANGIOGENESIS, G8794338893, G99091514
OpenAlex ID: W7124324909