px-478 and Aortic-Diseases

Hypoxia inducible factor 1α (HIF1α) plays a critical role in atherosclerosis as demonstrated in endothelial-targeted HIF1α -deficient mice. However, it has not been shown if specific pharmacological inhibitors of HIF1α can be used as potential drugs for atherosclerosis. PX-478 is a selective inhibitor of HIF1α, which was used to reduce cancer and obesity in animal models. Here, we tested whether PX-478 can be used to inhibit atherosclerosis.. PX-478 treatment reduced atherosclerotic plaque burden in the aortic trees in both mouse models, while plaque burden in the aortic sinus was reduced in the AAV-PCSK9 mouse model, but not in the ApoE. These results suggest that PX-478 is a potential anti-atherogenic drug, which targets vascular endothelium and hepatic cholesterol pathways.

Topics: Animals; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Disease Models, Animal; Endothelial Cells; Hypoxia; Mice; Mice, Inbred C57BL; Mice, Knockout; Mustard Compounds; Phenylpropionates; Plaque, Atherosclerotic; Proprotein Convertase 9