Abstract 15511: Kruppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility

Background: Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall [e.g., endothelial cells (ECs)] as well as circulating and resident immunogenic cells (e.g., monocytes/macrophages). Acting as a ligand for liver X receptor(LXR), but an inhibitor of sterol regulatory element binding protein 2(SREBP2), 25-hydroxycholesterol (25-HC) and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages. Methods: Bioinformatic analyses were used to investigate RNA-seqdata to identify cholesterol oxidation and efflux genes regulated by kruppel-like factor4 ( KLF4). In vitro experiments involving cultured ECs and macrophages and in vivo methods involving mice with Ch25h ablation were then used to explore the atheroprotective role of KLF4-Ch25h/LXR. Results: Vasoprotectivestimuli increased the expression of Ch25h and LXR via KLF4. The KLF4-Ch25h/LXR homeostat...