Bisphenol-A from environment macro-circulation to human micro-circulation: a novel link to abdominal aortic aneurysm

Area of Science:

• Environmental Health
• Toxicology
• Cardiovascular Research

Background:

• Fragmented research hinders understanding of environmental pollutant impacts on health.
• Emerging pollutants like bisphenol A (BPA) are linked to various pathogenic outcomes.
• A clear mechanistic link between BPA exposure and abdominal aortic aneurysm (AAA) is needed.

Purpose of the Study:

• To establish a systematic framework linking bisphenol A (BPA) exposure to abdominal aortic aneurysm (AAA) development.
• To elucidate the mechanistic pathways involved in BPA-induced AAA.
• To identify potential therapeutic targets for BPA-associated AAA.

Main Methods:

• Integrated exposure modeling and cellular validation.
• Cross-species multi-omics analysis to identify core molecular targets.
• In vivo validation of identified pathways and targets.

Main Results:

• Bisphenol A (BPA) promotes AAA development via TNF/NF-κB signaling pathways.
• BPA disrupts extracellular matrix remodeling, smooth muscle cell phenotype, inflammation, and senescence in vascular cells.
• Environmentally relevant BPA exposure alters key gene expression (e.g., Comp, Sele, Ets1) in vascular cells, with prognostic potential.

Conclusions:

• This study provides the first multiscale evidence chain linking environmental BPA exposure to AAA pathogenesis.
• The findings improve risk assessment for BPA and suggest novel prevention targets for BPA-associated AAA.
• Understanding these mechanisms is crucial for mitigating environmental health risks.