on December 20, 2007
Published online before print December 20, 2007, doi: 10.1161/ATVBAHA.107.143487
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 9, 2007
Accepted on December 1, 2007
Laminar Shear Stress Regulates Liver X Receptor in Vascular Endothelial Cells
Minjia Zhu ;
From the Department of Physiology and Pathophysiology (M.Z., Y.F., Y.H., Y.G., C.T., Y.Z.) and the Institute of Cardiovascular Research (N.W.), Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Health Science Center, Peking University, Beijing, China; and the Division of Biomedical Sciences (J.Y.-J.S.), University of California, Riverside.
* To whom correspondence should be addressed. E-mail: zhuyi{at}hsc.pku.edu.cn.
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/cm2). 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 and CYP27 RNAi. The decrease of LXR in the aorta of PPAR
+/- mice and that of C57 mice fed with PPAR antagonist suggest the involvement of PPAR in the LXR induction by flow.
Conclusion—Laminar flow increases LXR function via a PPAR-CYP27 dependent mechanism, which reveals an atheroprotective role for laminar flow exerting on endothelium.
Key words: shear stress • LXR • PPAR
•
endothelial cells