title: Activation of PPAR-δ induces microRNA-100 and decreases the uptake of very low-density lipoprotein in endothelial cells.
abstract: OBJECTIVE
  Increased level of very low-density lipoprotein (VLDL) is a key feature of the metabolic syndrome and is associated with cardiovascular diseases. PPAR-δ agonists play a protective role in lipid metabolism and vascular function. In this study, we aimed to investigate the role of PPAR-δ in the uptake of VLDL in endothelial cells and its underlying mechanism(s).
  
  
  METHODS
  Uptake of VLDL in HUVECs was assessed by Dil-fluorescent labelling of VLDL. Levels of VLDL receptor mRNA and microRNA (miR-100) were detected by quantitative PCR. The target genes of miR-100 were predicted using bioinformatics analysis. 3'-Untranslated region (3'-UTR) luciferase reporter and Argonaute 1 pull-down assays were used to validate the target of miR-100.
  
  
  RESULTS
  PPAR-δ agonist GW501516 decreased uptake of VLDL and expression of VLDL receptor at mRNA and protein levels. GW501516 inhibited the luciferase reporter activity of the 3'-UTR of VLDL receptor. VLDL receptor was a direct target of miR-100. miR-100 was significantly increased by GW501516 in HUVECs. Transfection of a miR-100 mimic decreased the mRNA and protein levels of VLDL receptor and uptake of VLDL. Furthermore, a miR-100 inhibitor abolished the inhibitory effect of PPAR-δ on VLDL receptor expression and VLDL uptake.
  
  
  CONCLUSIONS
  In endothelial cells, activation of PPAR-δ decreased VLDL receptor expression and VLDL uptake via the induction of miR-100. These results provided a novel mechanism for the vascular protective effect of PPAR-δ agonists.
authors: Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, China.|Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.
authors: Xi
authors: X
authors: Fang
authors: Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, China.
authors: Li
authors: L
authors: Fang
authors: Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, China.
authors: Ao
authors: A
authors: Liu
authors: Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, China.
authors: Xiaohong
authors: X
authors: Wang
authors: Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, China.
authors: Beilei
authors: B
authors: Zhao
authors: Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, China.|Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.
authors: Nanping
authors: N
authors: Wang
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047494:PPAR delta / Q000819:agonists / Q000502:physiology*; D011973:Receptors, LDL / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C425931:GW 501516; D008079:Lipoproteins, VLDL; C544266:MIRN100 microRNA, human; D035683:MicroRNAs; D047494:PPAR delta; D011973:Receptors, LDL; D013844:Thiazoles; C036053:VLDL receptor