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).


RESULTS
Western blot showed that the protein level of LXRalpha 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 LXRalpha and CYP27 RNAi. The decrease of LXR in the aorta of PPARgamma+/- mice and that of C57 mice fed with PPARgamma antagonist suggest the involvement of PPARgamma in the LXR induction by flow.


CONCLUSIONS
Laminar flow increases LXR function via a PPARgamma-CYP27 dependent mechanism, which reveals an atheroprotective role for laminar flow exerting on endothelium.
Zhu
Minjia
M
Department of Physiology and Pathophysiology, Peking University, Health Sciences Center, Beijing, China 100083.
Fu
Yi
Y
Hou
Yingjian
Y
Wang
Nanping
N
Guan
Youfei
Y
Tang
Chaoshu
C
Shyy
John Y-J
JY
Zhu
Yi
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013314:Stress, Mechanical; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear