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

Background: Vascular barrier breakdown in sepsis represents a key component of the maladaptive host response to infection and the release of endothelial Angiopoietin-2 (Angpt-2) is a mechanistic driver of endothelial hyperpermeability. Angpt-2 is associated with morbidity and mortality but a targeted therapeutic approach is not available. We screened for U.S. Food and Drug Administration (FDA) approved drugs that might have off-target effects decreasing Angpt-2 and therefore, ameliorating capillary leakage. Methods: Endothelial cells were isolated from human umbilical veins (HUVECs) and used for in vitro studies at baseline and after stimulation (FDA-library screening, RT-PCR, ELISA, immunocytochemistry, MTT assay). On the functional level, we assessed real-time transendothelial electrical resistance (TER) using an electric cell-substrate impedance sensing device. Results: We found that the anti-fungal Bifonazole (BIFO) reduces spontaneous Angpt-2 release in a time- and dose-dependent manner after 8, 12, and 24 h (24 h: veh: 15.6 ± 0.7 vs. BIFO: 8.6 ± 0.8 ng/mL, P 
Source: Shock - Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research