Off-Target Interactions of Vancomycin with Vascular Wall Involving Elastin-Induced Self-Assembly

Area of Science:

• Pharmacology
• Biomedical Engineering
• Molecular Biology

Background:

• Off-target drug effects cause side effects by interacting with non-target tissues.
• Vancomycin (Vanco) efficacy is limited by vascular injury, but its targets and mechanisms are unknown.

Purpose of the Study:

• To identify the molecular target and mechanism of vancomycin-induced vascular injury.
• To visualize vancomycin's behavior in vivo and its interaction with the vascular wall.

Main Methods:

• Multidimensional two-photon imaging was used to track fluorescently labeled vancomycin in vivo.
• Colocalization imaging and morphological analysis were employed to identify molecular interactions.

Main Results:

• Vancomycin directly interacts with elastin in the vascular wall.
• Vancomycin self-assembles into nanoaggregates on the elastic lamina.
• This binding and aggregation cause endothelial cytotoxicity and apoptosis.

Conclusions:

• Elastin is identified as the off-target molecular target of vancomycin in vascular injury.
• Vancomycin-elastin interactions and subsequent self-assembly drive cytotoxicity and apoptosis.
• Findings highlight the significance of drug-vascular interactions in clinical side effects.