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

Area of Science:

• Cardiovascular Science
• Endothelial Biology
• Psychoneuroimmunology

Background:

• Loneliness is a significant risk factor for cardiovascular disease (CVD).
• Endothelial barrier integrity is critical in CVD development.
• The specific impact of loneliness on endothelial function remains unclear.

Purpose of the Study:

• To investigate the relationship between loneliness and endothelial barrier integrity.
• To explore the mechanistic pathways linking loneliness to endothelial dysfunction.
• To assess the association between loneliness markers and subclinical CVD.

Main Methods:

• Measured perceived loneliness and its association with circulating epinephrine and TNFα (E/T).
• Assessed VE-cadherin expression on endothelial cells ex vivo.
• Analyzed plasma soluble VE-cadherin levels and subclinical CVD.
• Investigated E/T effects on endothelial barrier function and JAK/Stat signaling in vitro.

Main Results:

• Greater loneliness correlated with higher E/T levels.
• Higher E/T levels were associated with reduced endothelial VE-cadherin expression.
• Circulating soluble VE-cadherin levels were linked to subclinical CVD.
• In vitro E/T treatment impaired endothelial barrier integrity via JAK/Stat signaling.

Conclusions:

• Loneliness may contribute to CVD by compromising endothelial barrier integrity.
• Epinephrine and TNFα signaling represent a potential mechanism linking loneliness to endothelial dysfunction.
• These findings suggest chronic stress from loneliness could accelerate CVD progression.