Extracellular Vesicles Contribute to Oxidized LDL-Induced Stromal Cell Proliferation in Benign Prostatic Hyperplasia
Franco F. Roldán Gallardo,
Daniel E. Martínez Piñerez,
Kevin F. Reinarz Torrado,
Gabriela A. Berg,
Jael D. Herzfeld,
Vanina G. Da Ros,
Manuel López Seoane,
Cristina A. Maldonado,
Amado A. Quintar
Affiliations
Franco F. Roldán Gallardo
Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina
Daniel E. Martínez Piñerez
Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina
Kevin F. Reinarz Torrado
Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina
Gabriela A. Berg
Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1000, Argentina
Jael D. Herzfeld
Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires 1000, Argentina
Vanina G. Da Ros
Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires 1000, Argentina
Manuel López Seoane
Sanatorio Allende, Sede Nueva Córdoba, Córdoba 5000, Argentina
Cristina A. Maldonado
Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina
Amado A. Quintar
Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina
Background: Clinical and experimental evidence has linked Benign Prostatic Hyperplasia (BPH) with dyslipidemic and hypercholesterolemic conditions, though the underlying cellular mechanisms remain unclear. This study investigates the impact of dyslipidemia, specifically oxidized LDL (OxLDL), on prostatic stromal cell proliferation and the release of extracellular vesicles (EVs). Methods: Mice were fed a high-fat diet, and human prostatic stromal cells (HPSCs) were treated with OxLDL. Proliferation assays and EV characterization were performed to assess the role of EVs in BPH progression. Results: Pro-atherogenic conditions significantly increased cell proliferation in both murine prostatic cells and HPSCs. Treatment with metformin effectively inhibited OxLDL-induced proliferation. Additionally, OxLDL stimulated the production and release of pro-proliferative EVs by HPSCs, which further promoted cellular proliferation. Conclusions: The findings suggest that dyslipidemia drives prostatic stromal cell proliferation and EV secretion, contributing to BPH progression. Metformin demonstrates potential as a therapeutic agent to mitigate these effects, offering insight into novel strategies for BPH management. This study highlights the complex interaction between dyslipidemia, cell proliferation, and extracellular communication in the context of BPH pathogenesis.