Peroxisome proliferator-activated receptor a ligands increase lectin-like oxidized low density lipoprotein receptor-1 expression in vascular endothelial cells.
Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a receptor for atherogenic oxidized LDL expressed in vascular endothelial cells, smooth muscle cells, and macrophages. Peroxiosme proliferator-activated receptors (PPARs) include subfamilies PPARalpha and PPARgamma, which are expressed in endothelial cells and involved in transcriptional regulation of a large number of genes that affect lipoprotein and fatty acid metabolism as well as inflammation. We therefore explored the effects of PPARalpha and PPARgamma ligands on expression of LOX-1. Treatment of cultured bovine aortic endothelial cells (BAECs) with PPARalpha ligands (fenofibrate and WY14643) remarkably upregulated LOX-1 expression, which was detected by western and northern blot analyses. LOX-1 promoter-reporter gene assay showed that PPARalpha ligands activate transcription of the LOX-1 gene. PPARgamma ligands, in contrast, did not significantly affect LOX-1 expression in BAECs. PPARalpha appears to be a key regulator in promoting LOX-1 expression in BAECs. Upregulated expression of LOX-1 may modulate the catabolism of oxidized LDL and atherosclerotic progression.
Hayashida
K
K
Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, Japan.
Kume
N
N
Minami
M
M
Kataoka
H
H
Morimoto
M
M
Kita
T
T
D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D014157:Transcription Factors / Q000378:metabolism*
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D014157:Transcription Factors