[2015 SOT Conference Poster] Elucidating Mechanisms of Cardiovascular Toxicity Using Phenotypic Data from BioMAP Human Primary Cell Systems

[2015 SOT Conference Poster] Elucidating Mechanisms of Cardiovascular Toxicity Using Phenotypic Data from BioMAP Human Primary Cell Systems
File Name/Number:
2015 SOT Conference Poster

Year:
2015

We are applying a chemical biology approach for elucidating potential toxicity mechanisms for thrombosis-related side effects in humans. In previous work with the EPA for the ToxCast™ program, it was observed that several classes of chemicals, including aryl hydrocarbon receptor (AhR) agonists and estrogen receptor (ER) antagonists, shared a unique biomarker activity of increasing the cell surface levels of Tissue Factor (TF), the primary cellular initiator of coagulation, in a human primary endothelial cell-based model of vascular infl ammation, the BioMAP 3C system (Kleinstreuer et al., NBT, 2014, 32:583). Since human exposure to these chemical classes is associated with increased incidence of thrombosis-related side effects, it was of interest to search a large reference database for other compounds that also increase TF in an effort to better understand the regulation of tissue factor under these conditions and to potentially uncover mechanisms underlying clinical observations.