Laminar shear stress regulates liver X receptor in vascular endothelial cells

Objective-The liver X receptors (LXRs) regulate a set of genes involved in lipid metabolism and reverse cholesterol transport. We investigated the mechanism by which shear stress regulates LXR in vascular endothelial cells (ECs). Methods and Results-Western blot showed that the protein level of LXR and its target ABCA1 in the mouse thoracic aorta was higher than that in the aortic arch. As well, the mRNA level of LXR and its target genes ABCA1, ABCG1, ApoE, and LPL in the thoracic aorta was higher. In vitro, bovine aortic ECs were subjected to a steady laminar flow (12 dyne/cm(2)). The expressions of LXR and the LXR-mediated transcription were increased by laminar shear stress. Laminar flow increased LXR-ligand binding and the gene expression of sterol 27-hydroxylase (CYP27), which suggests an increased level of LXR ligand in ECs. This effect was attenuated by LXR alpha and CYP27 RNAi. The decrease of LXR in the aorta of PPAR gamma(-/-) mice and that of C57 mice fed with PPAR gamma antagonist suggest the involvement of PPAR gamma in the LXR induction by flow. Conclusion-Laminar flow increases LXR function via a PPAR gamma-CYP27 dependent mechanism, which reveals an atheroprotective role for laminar flow exerting on endothelium.