Human Breast Milk Extracellular Vesicles Mitigate Endothelial Dysfunction

Young-Eun Cho; Shaoshuai Chen; Keith Crouch; Damon Shutt; Justin W. Kaufman; Brajesh K. Singh

doi:10.3390/nu17182953

Back

Human Breast Milk Extracellular Vesicles Mitigate Endothelial Dysfunction

Journal article

Open access

Peer reviewed

Human Breast Milk Extracellular Vesicles Mitigate Endothelial Dysfunction

Young-Eun Cho, Shaoshuai Chen, Keith Crouch, Damon Shutt, Justin W. Kaufman and Brajesh K. Singh

Nutrients, Vol.17(18), 2953

09/13/2025

DOI: 10.3390/nu17182953

PMCID: PMC12472446

PMID: 41010478

Files and links (1)

url

https://doi.org/10.3390/nu17182953View

Published (Version of record) Open Access

Abstract

Background: Endothelial cell (EC) dysfunction is an early sign of compromised vascular integrity and is associated with various cardiovascular diseases (CVDs). Activation of Toll-like receptor 4 (TLR4) plays a central role in this process. Extracellular vesicles (EVs) derived from milk have known anti-inflammatory properties, particularly in suppressing TLR4 activation. This study investigates the therapeutic potential of human breast milk-derived EVs (HBM-EVs) in mitigating EC dysfunction related to CVDs. Methods: HBM-EVs were isolated from the breast milk of healthy nursing mothers using ultracentrifugation. HBM-EVs were applied to lipopolysaccharide (LPS)-treated human umbilical vein endothelial cells (HUVECs), and inflammatory marker expression was assessed through qPCR and Western blotting. Mitochondrial oxidative stress was measured using MitoSOX. The effects of HBM-EVs were further evaluated in ex vivo studies using mesenteric arteries from diet-induced obese mice. Additionally, the effect of HBM-EVs on angiogenesis was tested via a wound closure assay. Results: In HUVECs, pre-treatment with HBM-EVs inhibited LPS-induced expression of inflammatory markers, including IL-6 and VCAM-1, as well as the phosphorylation of NFκB. Additionally, HBM-EVs reduced LPS-induced mitochondrial oxidative stress. In animal studies, HBM-EV treatment restored EC-dependent vasorelaxation in mesenteric arteries from diet-induced obese mice. Furthermore, HBM-EVs enhanced EC migration, leading to improved wound closure in HUVECs. Conclusion: This study demonstrates the therapeutic potential of HBM-EVs in alleviating EC dysfunction, offering a promising new approach to the treatment of CVDs. Future research will focus on identifying the specific cargo of HBM-EVs and further exploring their therapeutic mechanisms in endothelial dysfunction.

human breast milk extracellular vesicles

exosomes

endothelial dysfunction

inflammation

oxidative stress

Details

Title: Subtitle: Human Breast Milk Extracellular Vesicles Mitigate Endothelial Dysfunction
Creators: Young-Eun Cho
Shaoshuai Chen - University of Iowa
Keith Crouch - University of Iowa
Damon Shutt - University of Iowa
Justin W. Kaufman - University of Iowa
Brajesh K. Singh - University of Iowa
Resource Type: Journal article
Publication Details: Nutrients, Vol.17(18), 2953
DOI: 10.3390/nu17182953
PMID: 41010478
PMCID: PMC12472446
NLM abbreviation: Nutrients
ISSN: 2072-6643
eISSN: 2072-6643
Publisher: MDPI
Grant note: Fraternal Order of Eagles Diabetes Research CenterDepartment of Pediatrics, University of Iowa
This research was funded by the Fraternal Order of Eagles Diabetes Research Center and Savvy Ferentz research award from Department of Pediatrics, University of Iowa (No funding numbers).
Language: English
Date published: 09/13/2025
Academic Unit: Stead Family Department of Pediatrics; Pathology; Nursing; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984963628002771

Metrics

12 Record Views