The role of the hypoxia-inducible lipid droplet protein Hig2/Hilpda in macrophages and endothelial cells in the development of atherosclerosis
During our work on the respective contribution of HIF-1 α, HIF-2 α and HIF-3 α to hypoxic gene induction we recently identified the hypoxia-inducible gene 2 (HIG2) as a novel lipid droplet protein (Gimm et. al., FASEB J. 2010). HIG2, which was subsequently renamed HILPDA (hypoxia-inducible lipid droplet-associated protein), is a ubiquitous HIF target gene and mediates the hypoxic accumulation of triglycerides and cholesteryl esters, which is detectable in almost all cell types.
HIG2/HILPDA is highly expressed in macrophage foam cells in human atherosclerotic plaques. HIF is known to be activated in atherosclerotic blood vessels by hypoxia and by pro-inflammatory signaling pathways and to contribute to the progression of atherosclerosis through induction of a multitude of target genes. Therefore, we presently investigate in Apolipoprotein E-deficient mice whether a conditional knockout of Hig2/Hilpda affects the development of atherosclerosis.
Moreover, we are working on the characterization of FAM13A1, another HIF target gene with unknown function.
Our studies thus complement the projects of the other groups in our department that characterize the hypoxic gene response in vitro, as well as the role of HIF in kidney diseases and the protective effects of pharmacological HIF activation in animal models.