Document Type

Article

Publication Date

2025

DOI

10.1038/s44325-025-00059-5

Publication Title

npj Cardiovascular Health

Volume

2

Issue

1

Pages

28 (1-11)

Abstract

Loneliness is known to be an important contributor to cardiovascular disease (CVD). However, little is known about the impact of loneliness on endothelial barrier integrity, a crucial hallmark of CVD development and progression. In this study, we aimed to investigate how loneliness might impact the endothelium. We found greater perceived loneliness associated with the product of circulating epinephrine and TNFα (E/T), which, in turn, associated with lower VE-cadherin on endothelial cells in an ex vivo experiment. Additionally, circulating plasma levels of soluble VE-cadherin were associated significantly with subclinical CVD. To explore the mechanistic aspects of these associations, we measured the effects of E/T on endothelial barrier function in vitro. E/T treatment decreased endothelial VE-cadherin expression and dampened endothelial barrier integrity, involving at least partial JAK/Stat signaling, highlighting a potential additive effect of epinephrine and TNFα on endothelial dysfunction, potentially accelerating CVD development and progression in individuals experiencing loneliness-related chronic stress.

Rights

This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Data Availability

Article states: Data availability: "The data pertaining to this study are available from the corresponding author upon reasonable request and within the IRB guidelines for the study protocol."

Original Publication Citation

Baumer, Y., Tirado, B. A., Ortiz-Whittingham, L. R., Baez, A. S., Gutierrez-Huerta, C. A., Mendelsohn, L. G., Saurabh, A., Jacobs, J. A., Andrews, M. R., Mitchell, V. M., Collins, B. S., Jones, A., Schwartz, D. M., Dobrian, A. D., Stanton, M. V., & Powell-Wiley, T. M. (2025). Loneliness associates with endothelial dysfunction in a community-based cohort: A pilot study and translational approach. npj Cardiovascular Health, 2(1), 1-11, Article 28. https://doi.org/10.1038/s44325-025-00059-5

44325_2025_59_MOESM1_ESM.pdf (2389 kB)
Supplementary Data

44325_2025_59_MOESM2_ESM.pdf (385 kB)
Supplementary Data 4A

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