Transcriptional Regulation of Drug Metabolizing CYP Enzymes by Proinflammatory Wnt5A Signaling in Human Coronary Artery Endothelial Cells

Downregulation of drug metabolizing enzymes and transporters by proinflammatory mediators in hepatocytes, enterocytes renal tubular epithelium is an established mechanism affecting pharmacokinetics. Emerging evidences indicate that vascular endothelial cell expression may regulate pharmacokinetic pathways heart to modulate local bioavailability toxicity. However, whether inflammation regulates human cardiac cells remains largely unknown. The lipid modified protein Wnt5A emerging as a critical mediator responses disease severity sepsis, hypertension COVID-19. In the present study, we employed transcriptome profiling gene ontology analyses investigate regulation coronary artery cells. Our study shows for first time induces CYP1A1 CYP1B1 involved phase I metabolism broad spectrum drugs including chloroquine (the controversial COVID-19) known cause toxicity myocardium. Further, upregulation preserved even during inflammatory crosstalk between prototypic IL-1β These findings stimulate further studies test roles CYP1B1, potential vascular-targeted therapy with CYP1A1/CYP1B1 inhibitors modulating myocardial pharmacokinetics Wnt5A-associated cardiovascular diseases.