Human Breast Milk Extracellular Vesicles Mitigate Endothelial Dysfunction.

Area of Science:

• Cardiovascular Research
• Cell Biology
• Nanomedicine

Background:

• Endothelial cell (EC) dysfunction is a key early indicator of cardiovascular diseases (CVDs).
• Toll-like receptor 4 (TLR4) activation significantly contributes to EC dysfunction.
• Extracellular vesicles (EVs) from human breast milk (HBM-EVs) possess anti-inflammatory properties.

Purpose of the Study:

• To investigate the therapeutic potential of HBM-EVs in mitigating endothelial cell dysfunction relevant to CVDs.
• To assess the impact of HBM-EVs on inflammatory pathways and oxidative stress in endothelial cells.
• To evaluate the efficacy of HBM-EVs in restoring vascular function and promoting angiogenesis.

Main Methods:

• Isolation of HBM-EVs via ultracentrifugation from healthy donors.
• Treatment of lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) with HBM-EVs.
• Assessment of inflammatory markers (IL-6, VCAM-1), NFκB phosphorylation, and mitochondrial oxidative stress (MitoSOX).
• Ex vivo studies on mesenteric arteries from diet-induced obese mice and in vitro angiogenesis assays (wound closure).

Main Results:

• HBM-EVs significantly inhibited LPS-induced IL-6 and VCAM-1 expression and NFκB phosphorylation in HUVECs.
• HBM-EVs reduced mitochondrial oxidative stress in LPS-treated HUVECs.
• HBM-EV treatment restored endothelial cell-dependent vasorelaxation in obese mouse arteries and enhanced EC migration and wound closure.

Conclusions:

• HBM-EVs demonstrate significant therapeutic potential for alleviating endothelial cell dysfunction.
• HBM-EVs represent a promising novel approach for the treatment of cardiovascular diseases.
• Further research is warranted to identify HBM-EV cargo and elucidate detailed therapeutic mechanisms.