Loneliness associates with endothelial dysfunction in a community-based cohort: a pilot study and translational...

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.