OxLDL promotes stromal cell proliferation in Benign Prostatic Hyperplasia mediated by extracellular vesicles

FRANCO ROLDÁN GALLARDO; DANIEL MARTINEZ PIÑEREZ; KEVIN REINARZ TORRADO; GABRIELA BERG; VANINA DA ROS; MANUEL LOPEZ SEOANE; CRISTINA MALDONADO; AMADO QUINTAR

PROSTATE CANCER AND PROSTATIC DISEASES

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2024

1365-7852

AbtractIntroduction: Benign Prostatic Hyperplasia (BPH), characterized by uncontrolled cell proliferation in the prostatic transitional zone, is a prevalent condition associated with urinary symptoms. The pro-atherogenic environment has emerged as a potential contributor to BPH pathogenesis, prompting further investigation into its underlying mechanisms.Objectives: This study aimed to explore the impact of pro-atherogenic states on prostatic stromal cell proliferation and investigate potential therapeutic interventions.Methodology: Murine models were exposed to pro-atherogenic conditions, while human prostatic stromal cells (HPSC) were subjected to oxidized-LDL (OxLDL) in vitro. Proliferation assays and extracellular vesicles (EVs) characterization were conducted to elucidate the involvement of EVs in the BPH pathogenesis.Results: Pro-atherogenic conditions induced significant proliferation in murine prostatic cells and HPSC, while metformin demonstrated a mitigating effect on OxLDL-induced proliferation. Additionally, OxLDL augmented EV production and release by HPSC, thereby promoting further proliferation, highlighting a potential mechanism underlying BPH progression.Conclusion: The findings suggest a role for the pro-atherogenic environment in driving prostatic cell proliferation and EV production, potentially influencing BPH progression. Metformin emerges as a promising therapeutic avenue for BPH management. This study underscores the intricate interplay between dyslipidemia, cell proliferation, and therapeutic targets in BPH pathogenesis.