S1 - Symposium 1

Molecular messengers of disease: How extracellular vesicles shape smooth muscle cell behavior in prostate and Vascular hyperproliferative diseases

Quintar, Amado Alfredo

INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD, CENTRO CIENTIFICO TECNOLOGICO (CONICET), CONSEJO NACIONAL DE INVESTIGACIONES CIENTIFICAS Y TECNICAS, CORDOBA
Contacto: no_mail

 Benign prostatic hyperplasia (BPH) and vascular occlusive diseases share pathological hallmarks involving dysregulated smooth muscle cell (SMC) proliferation and altered intercellular communication. Extracellular vesicles (EVs) have emerged as pivotal mediators linking metabolic stress to hyperproliferative responses in multiple tissues. Our results demonstrated that in the prostate, oxidized low-density lipoprotein (OxLDL) promotes stromal cell proliferation in both high-fat diet–fed mice and cultured human prostatic SMCs, an effect driven in part by OxLDLinduced EV release. In vitro, these EVs contained proliferation-associated miRNAs and exhibited pro-proliferative properties, while metformin effectively suppressed OxLDL-stimulated SMC proliferation, suggesting a potential therapeutic avenue for BPH progression. In vascular biology, the atypical cadherin FAT1—previously shown to dampen SMC proliferation via mitochondrial metabolism—also exerts paracrine effects through EVs. FAT1 was detected in EVs derived from bovine, murine, and human SMCs, where FAT1-positive EVs inhibited proliferation of FAT1- deficient cells, whereas EVs from FAT1-deficient SMCs lacked this anti-proliferative activity. Importantly, FAT1-containing EVs were also identified in plasma samples from patients with chronic kidney disease (CKD), a condition associated with accelerated vascular remodeling, underscoring their clinical relevance. Together, these findings highlight EVs as critical modulators of cellular growth in both prostate and vascular contexts, capable of transmitting either pro- or anti-proliferative signals depending on their molecular cargo. The integration of metabolic cues (e.g., OxLDL, metformin) and structural regulators (e.g., FAT1) into EV-mediated communication reveals shared mechanisms by which systemic and local factors drive disease progression.