Aksoy, Z. B.; Aydos, D.; Kocakaya, E.; Uyar, R.; Turan, B.; Bitirim, C. V.

Cardiovascular diseases (CVDs) are among the disease groups with the highest mortality rates; therefore, the development of effective cardioprotective applications is of utmost importance. Estrogen (E2) plays a crucial role in cardiac remodeling and is known for its cardioprotective effects. However, the impact of E2 on the cargo composition of extracellular vesicles (EVs) derived from cardiac progenitor cells (CPCs) has not been fully elucidated. While CPC-derived EVs contribute to myocardial regeneration and cardioprotection, their paracrine therapeutic efficacy has not been comprehensively defined. Here, we investigated how E2 regulates the miRNA cargo of CPC-derived EVs. Our findings indicate that E2 enhances the expression of miR-146, miR-23, miR-21, miR-132, and miR-148-miRNAs known to support angiogenesis. Conversely, the decrease in the expression of miR-208 leads to a role in cardiac remodeling. These E2-induced alterations in EV cargo composition highlight the role of E2 in establishing a cardioprotective EV profile and promoting myocardial recovery. Additionally, transcriptomic analysis of CPCs following E2 treatment revealed differential expression changes aligned with CPC EV cargo activity. Understanding the molecular changes occurring both intracellularly and in EV content following E2 treatment has the potential to offer a novel perspective in the development of stem cell-based therapies for cardiovascular diseases.