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bioRxiv · 10.1101/2024.05.20.594769

Human Breast Milk EVs Mitigate Endothelial Dysfunction: Preliminary Study

Cho, Y.-E.·Chen, S.·Shutt, D.·Kaufman, J.·Singh, B.
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Abstract

BackgroundEndothelial cell (EC) dysfunction is an early indicator of failing vascular integrity, leading to various cardiovascular diseases. Toll-like receptor 4 (TLR4) activation is a key mechanism. Milk-derived extracellular vesicles (EVs) are known for their anti-inflammatory properties, particularly in suppressing TLR4 activation in damaged intestinal epithelial cells. This study explores the therapeutic potential of human breast milk EVs (bEVs) in EC dysfunction related to cardiovascular diseases. MethodsHuman breast milk EVs (bEVs) were isolated from healthy nursing mothers using ultracentrifugation. bEVs were applied to LPS-treated HUVECs, and the expression of inflammatory markers was measured using qPCR and western blotting. Angiogenesis was assessed via a wound assay. Additionally, bEVs were orally administered weekly for six weeks to high-fat diet-induced obese mice and lean mice. Metabolic phenotype characteristics and EC-dependent vasorelaxation were evaluated. ResultsbEV pre-treatment inhibited LPS-induced expression of inflammatory genes, including IL-6, IL-1b and VCAM-1. It also suppressed phospho-NFkB and TLR4 protein expression. bEVs enhanced EC migration, significantly increasing wound closure. Oral administration of bEVs restored impaired EC-dependent vasorelaxation in the mesenteric artery of obese mice, though metabolic parameters remained unchanged. ConclusionOur findings demonstrate the beneficial effects of bEVs on EC dysfunction, highlighting their potential as novel therapeutics for cardiovascular diseases. Future studies will focus on identifying specific bEV cargos and further evaluating their therapeutic effects on EC dysfunction.

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Cho, Y.-E., Chen, S., Shutt, D., Kaufman, J., Singh, B.. 2024-05-21. Human Breast Milk EVs Mitigate Endothelial Dysfunction: Preliminary Study. https://doi.org/10.1101/2024.05.20.594769

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