PMID- 27644038
OWN - NLM
STAT- MEDLINE
DCOM- 20170407
LR  - 20181202
IS  - 1476-511X (Electronic)
IS  - 1476-511X (Linking)
VI  - 15
IP  - 1
DP  - 2016 Sep 19
TI  - Advanced glycation end products increase lipids accumulation in macrophages 
      through upregulation of receptor of advanced glycation end products: increasing 
      uptake, esterification and decreasing efflux of cholesterol.
PG  - 161
LID - 10.1186/s12944-016-0334-0 [doi]
LID - 161
AB  - BACKGROUND: Previous reports have suggested that advanced glycation end products 
      (AGEs) participate in the pathogenesis of diabetic macroangiopathy. Our previous 
      study have found that AGEs can increase the lipid droplets accumulation in aortas 
      of diabetic rats, but the current understanding of the mechanisms remains 
      incomplete by which AGEs affect lipids accumulation in macrophages and accelerate 
      atherosclerosis. In this study, we investigated the role of AGEs on lipids 
      accumulation in macrophages and the possible molecular mechanisms including 
      cholesterol influx, esterification and efflux of macrophages. METHODS: THP-1 
      cells were incubated with PMA to differentiate to be macrophages which were 
      treated with AGEs in the concentration of 300 mug/ml and 600 mug/ml with or without 
      anti-RAGE (receptor for AGEs) antibody and then stimulated by oxidized-LDL 
      (oxLDL) or Dil-oxLDL. Lipids accumulation was examined by oil red staining. The 
      cholesterol uptake, esterification and efflux were detected respectively by 
      fluorescence microscope, enzymatic assay kit and fluorescence microplate. 
      Quantitative RT-PCR and Western blot were used to measure expression of the 
      moleculars involved in cholesterol uptake, synthesis/esterification and efflux. 
      RESULTS: AGEs increased lipids accumulation in macrophages in a 
      concentration-dependent manner. 600 mug/ml AGEs obviously upregulated oxLDL 
      uptake, increased levels of cholesterol ester in macrophages, and decreased the 
      HDL-mediated cholesterol efflux by regulating the main molecular expression 
      including CD36, Scavenger receptors (SR) A2, HMG-CoA reductase (HMGCR), ACAT1 and 
      ATP-binding cassette transporter G1 (ABCG1). The changes above were inversed when 
      the cells were pretreated with anti-RAGE antibody. CONCLUSIONS: The current study 
      suggest that AGEs can increase lipids accumulation in macrophages by regulating 
      cholesterol uptake, esterification and efflux mainly through binding with RAGE, 
      which provide a deep understanding of mechanisms how AGEs accelerating diabetic 
      atherogenesis.
FAU - Xu, Lei
AU  - Xu L
AD  - Department of Endocriology and Metabolic Disease, East Hospital, Tongji 
      University School of Medicine, Shanghai, 200120, China.
FAU - Wang, Yi-Ru
AU  - Wang YR
AD  - Tongji University School of Medicine, Shanghai, 200120, China.
FAU - Li, Pei-Cheng
AU  - Li PC
AD  - Tongji University School of Medicine, Shanghai, 200120, China.
FAU - Feng, Bo
AU  - Feng B
AD  - Department of Endocriology and Metabolic Disease, East Hospital, Tongji 
      University School of Medicine, Shanghai, 200120, China. fengbo201607@126.com.
AD  - , Ji-mo Road 150, Shanghai, 200120, China. fengbo201607@126.com.
LA  - eng
PT  - Journal Article
DEP - 20160919
PL  - England
TA  - Lipids Health Dis
JT  - Lipids in health and disease
JID - 101147696
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (Abcg1 protein, rat)
RN  - 0 (Ager protein, rat)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (oxidized low density lipoprotein)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
RN  - EC 2.3.1.9 (ACAT1 protein, rat)
RN  - EC 2.3.1.9 (Acetyl-CoA C-Acetyltransferase)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1/biosynthesis
MH  - Acetyl-CoA C-Acetyltransferase/biosynthesis
MH  - Animals
MH  - Cholesterol/*metabolism
MH  - Diabetes Mellitus, Experimental/genetics/*metabolism/pathology
MH  - Diabetic Angiopathies/genetics/*metabolism/pathology
MH  - Esterification
MH  - Gene Expression Regulation
MH  - Glycation End Products, Advanced/metabolism
MH  - Humans
MH  - Hydroxymethylglutaryl CoA Reductases/biosynthesis
MH  - Lipid Metabolism/*genetics
MH  - Lipoproteins, LDL/metabolism
MH  - Macrophages/metabolism/pathology
MH  - Rats
MH  - Receptor for Advanced Glycation End Products/*genetics/metabolism
PMC - PMC5028926
OTO - NOTNLM
OT  - AGEs
OT  - Atherosclerosis
OT  - Cholesterol
OT  - Diabetes
OT  - Macrophages
OT  - RAGE
EDAT- 2016/09/20 06:00
MHDA- 2017/04/08 06:00
PMCR- 2016/09/19
CRDT- 2016/09/20 06:00
PHST- 2016/07/27 00:00 [received]
PHST- 2016/09/14 00:00 [accepted]
PHST- 2016/09/20 06:00 [entrez]
PHST- 2016/09/20 06:00 [pubmed]
PHST- 2017/04/08 06:00 [medline]
PHST- 2016/09/19 00:00 [pmc-release]
AID - 10.1186/s12944-016-0334-0 [pii]
AID - 334 [pii]
AID - 10.1186/s12944-016-0334-0 [doi]
PST - epublish
SO  - Lipids Health Dis. 2016 Sep 19;15(1):161. doi: 10.1186/s12944-016-0334-0.