Extracellular vesicles mediate OxLDL-induced stromal cell proliferation in Benign Prostatic Hyperplasia

2 Abstract Background Clinical and basic research evidence has suggested a possible linkage of Benign Prostatic Hyperplasia (BPH) to proatherogenic conditions such as dyslipedemia and hypercholesterolemia, but the underlying mechanisms remain still unknown. We here aimed to explore the impact of dyslipidemic contexts on prostatic stromal cell proliferation and on the release of extracellular vesicles (EVs). Methods Mice were exposed to a high-fat diet and human prostatic stromal cells (HPSC) subjected to oxidized-LDL (OxLDL). Cell proliferation assays and EV characterization were performed to elucidate the involvement of EVs in the BPH. Results Pro-atherogenic conditions significantly induced 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. Conclusions The findings suggest that pro-atherogenic conditions contributes to prostatic cell proliferation and EV production, 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.