title: GABA and topiramate inhibit the formation of human macrophage-derived foam cells by modulating cholesterol-metabolism-associated molecules.
abstract: OBJECTIVE
  γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs).
  
  
  METHODS
  ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model.
  
  
  RESULTS
  GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-α was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL)-6 did not change. The activation of two signaling pathways, p38MAPK and NF-κB, was repressed by GABA and topiramate in lipid-laden HMDMs.
  
  
  CONCLUSIONS
  GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions.
authors.affiliation: Department of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Yi-Tian
authors.initials: YT
authors.lastname: Lian
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Long-Xian
authors.initials: LX
authors.lastname: Cheng
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000077236:Topiramate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D018696:Neuroprotective Agents; C495137:OLR1 protein, human; D051117:Scavenger Receptors, Class A; D051127:Scavenger Receptors, Class E; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D000077236:Topiramate; D005632:Fructose; D005680:gamma-Aminobutyric Acid; D002784:Cholesterol; D048051:p38 Mitogen-Activated Protein Kinases