A possible mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs), aryl hydrocarbon receptor (AHR) ligands, induce atherogenesis. Liver X receptor (LXR) alpha is known to be involved in the control of cholesterol homeostasis. Thus, the purpose of this study was to investigate the effects of 3-methlycholanthrene (MC), one of the PAHs, on LXRalpha-mediated signal transductions. We found that expression of mRNAs for ATP binding cassette A1, sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase, and stearoyl-CoA desaturase was suppressed by treatment of HepG2 cells with MC. A luciferase reporter assay revealed that LXRalpha- and SREBP-1c-mediated transactivations were inhibited by MC via AHR. Based on these lines of evidence, we propose that down-regulation of the LXRalpha-regulated genes by PAHs is one of the causes responsible for atherosclerosis induced by PAHs.