Modulation of the Permeability-Inducing Factor Angiopoietin-2 Through Bifonazole in Systemic Inflammation

Area of Science:

• Vascular biology
• Pharmacology
• Sepsis research

Background:

• Vascular barrier breakdown in sepsis increases mortality.
• Endothelial Angiopoietin-2 (Angpt-2) drives hyperpermeability.
• No targeted therapies exist for Angpt-2-mediated vascular leakage.

Purpose of the Study:

• Screen FDA-approved drugs for potential to reduce Angpt-2.
• Investigate Bifonazole's effect on Angpt-2 release and vascular permeability.
• Identify novel therapeutic strategies for sepsis-induced vascular dysfunction.

Main Methods:

• Screened FDA-approved drug library for compounds affecting Angpt-2.
• Utilized human umbilical vein endothelial cells (HUVECs) for in vitro assays.
• Assessed Angpt-2 levels via ELISA and RT-PCR.
• Measured endothelial permeability using transendothelial electrical resistance (TER).

Main Results:

• Bifonazole (BIFO) significantly reduced spontaneous and TNFα-induced Angpt-2 release.
• BIFO decreased intracellular Angpt-2 levels by 33%.
• BIFO treatment ameliorated thrombin-induced endothelial barrier breakdown.

Conclusions:

• The antifungal Bifonazole (BIFO) inhibits Angpt-2 release and biosynthesis in vitro.
• BIFO enhances vascular barrier function, suggesting therapeutic potential.
• Further in vivo and mechanistic studies are warranted.