Extracellular Vesicles Contribute to Oxidized LDL-Induced Stromal Cell Proliferation in Benign Prostatic Hyperplasia

Simple Summary Benign Prostatic Hyperplasia (BPH) is a prevalent condition among aging men, and recent research suggests it may be influenced by high cholesterol levels, especially oxidized LDL (OxLDL). However, how this happens is still not fully understood. This study aimed to explore how elevated OxLDL levels affect prostate cell growth and the release of small particles called extracellular vesicles (EVs), which cells use to communicate. By studying mice on a high-fat diet and human prostate cells exposed to OxLDL, we found that these conditions led to increased cell growth, potentially worsening BPH. We also discovered that OxLDL stimulated the production of EVs, further promoting cell proliferation. However, the drug metformin, commonly used to treat diabetes, was able to reduce this harmful growth. These findings provide new insights into how OxLDL may drive BPH progression and suggest that metformin could be a promising treatment to delay its development, potentially benefiting many men worldwide.Abstract 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.