title: Receptor mediated elevation in FABP4 levels by advanced glycation end products induces cholesterol and triacylglycerol accumulation in THP-1 macrophages.
abstract: Excessive formation of advanced glycation end products (AGE) and lipid accumulation in macrophages play a pivotal role in the progression of atherosclerosis in diabetes mellitus. This study aimed to determine the molecular link between AGE-induced fatty acid binding protein 4 (FABP4) expression and macrophage lipid accumulation. AGE-BSA markedly increased macrophage FABP4 expression via engagement of RAGE, a 35-kDa transmembrane receptor that is able to bind extracellular AGE and responsible for the corresponding signal transduction, whereas knockdown of RAGE significantly reversed the FABP4 up-regulation. This effect was further paralleled with elevated intracellular total cholesterol and triacylglycerol levels. Finally, administration of FABP4 inhibitor totally abolished the increased lipid contents in response to AGE-BSA. These results indicate that FABP4 up-regulation is responsible for the enhanced macrophage lipid accumulation by AGE, which may underlie the accelerated formation of foam cells and development of atherosclerotic cardiovascular diseases in diabetic patients.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, People's Republic of China.
authors.forename: Xiao Qun
authors.initials: XQ
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Yu Song
authors.initials: YS
authors.lastname: He
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Wei Feng
authors.initials: WF
authors.lastname: Shen
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism*
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D017127:Glycation End Products, Advanced; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014280:Triglycerides; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D002784:Cholesterol