Endothelial extracellular vesicles preserve vascular smooth muscle cell identity but do not reverse endothelial senescence.

Úrsula Zúñiga-Cuevas, Vania Otárola-Urrutia, Leslye Venegas-Zamora, Magda C Díaz-Vesga, Camila López-Torres, Javiera Favi-Coloma, Constanza Rimassa-Taré, Ximena Calle-Chalco, Andrés Ramírez-Reyes, Alejandra Hernández, Danica Jiménez-Gallegos, Sebastián Urquiza-Zurich, Mayarling F Troncoso, Ignacio Norambuena-Soto, Mario Chiong, Valentina Parra, Sergio Lavandero, Jaime A Riquelme

Laboratory of Cardiovascular Pharmacotherapy, Departamento de Quimica Farmacologica y Toxicologica, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.Laboratory of Cardiovascular Pharmacotherapy, Departamento de Quimica Farmacologica y Toxicologica, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Santiago, Chile. · pubmed

Paper

Abstract

Vascular aging is characterized by endothelial senescence and vascular smooth muscle cell (VSMC) phenotypic switching, yet the role of endothelial extracellular vesicles (EVs) in these processes remains unclear. We show that EVs from non-senescent endothelial cells prevent PDGF-BB-induced VSMC dedifferentiation, preserving contractile markers and limiting migration. In endothelial cells, EVs protected against TNF-α-induced eNOS downregulation but failed to reverse inflammatory and mitochondrial features of senescence after short-term exposure, highlighting a context-dependent protective role.

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Research summary

Endothelial extracellular vesicles from non-senescent cells preserve vascular smooth muscle cell identity and partially protect endothelial cells from inflammatory stress, but fail to reverse established senescence markers. This study provides incremental mechanistic insight into intercellular communication in vascular aging, highlighting the limitations of EV-based reversal strategies for established senescence.

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