PMID- 17005185
OWN - NLM
STAT- MEDLINE
DCOM- 20070717
LR  - 20181201
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 192
IP  - 2
DP  - 2007 Jun
TI  - AGE-BSA decreases ABCG1 expression and reduces macrophage cholesterol efflux to 
      HDL.
PG  - 298-304
AB  - BACKGROUND: Previous reports have suggested that advanced glycation end products 
      (AGE) participate in the pathogenesis of diabetic macroangiopathy. However, 
      current understanding of the mechanisms by which AGE may accelerate atherogenesis 
      remains incomplete. METHODS AND RESULTS: Microarray and reverse transcription 
      real-time PCR analyses revealed that exposure to AGE-BSA (BSA, bovine serum 
      albumin) reduced mRNA levels (60%) in the ATP-binding cassette transporter G1 
      (ABCG1) but not ABCA1 in human macrophages. AGE-BSA also reduced ABCG1 protein 
      levels. These effects occurred mainly through the receptor for AGE (RAGE), as an 
      anti-RAGE antibody significantly limited ABCG1 mRNA reduction. Functional studies 
      demonstrated that exposure to AGE-BSA decreased cholesterol efflux to 
      high-density lipoprotein (HDL) (P<0.05) but not to apolipoprotein AI, compared to 
      BSA treatment. Although liver X receptors (LXR) augment ABCG1 expression, 
      macrophages treated with AGE-BSA showed no reduction in LXR mRNA levels or in the 
      binding of nuclear proteins to the LXR response element, compared with BSA. 
      CONCLUSIONS: Our data show that AGE-BSA can decrease cholesterol efflux from 
      macrophages to HDL via an LXR-independent pathway. This novel mechanism may 
      contribute to accelerated foam cell production and atherogenesis in diabetic 
      patients.
FAU - Isoda, Kikuo
AU  - Isoda K
AD  - Donald W. Reynolds Cardiovascular Clinical Research Center, Brigham and Women's 
      Hospital and Harvard Medical School, Boston, MA 02115, USA.
FAU - Folco, Eduardo J
AU  - Folco EJ
FAU - Shimizu, Koichi
AU  - Shimizu K
FAU - Libby, Peter
AU  - Libby P
LA  - eng
GR  - GM-67049/GM/NIGMS NIH HHS/United States
GR  - HL-67249/HL/NHLBI NIH HHS/United States
GR  - HL-67283/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060926
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Liver X Receptors)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (advanced glycation end products-bovine serum albumin)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/*biosynthesis
MH  - Cholesterol/*metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Glycation End Products, Advanced/*pharmacology
MH  - Humans
MH  - Lipoproteins, HDL/*metabolism
MH  - Liver X Receptors
MH  - Macrophages/drug effects/*physiology
MH  - Orphan Nuclear Receptors
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Serum Albumin, Bovine/*pharmacology
EDAT- 2006/09/29 09:00
MHDA- 2007/07/18 09:00
CRDT- 2006/09/29 09:00
PHST- 2006/04/19 00:00 [received]
PHST- 2006/07/06 00:00 [revised]
PHST- 2006/07/21 00:00 [accepted]
PHST- 2006/09/29 09:00 [pubmed]
PHST- 2007/07/18 09:00 [medline]
PHST- 2006/09/29 09:00 [entrez]
AID - S0021-9150(06)00445-X [pii]
AID - 10.1016/j.atherosclerosis.2006.07.023 [doi]
PST - ppublish
SO  - Atherosclerosis. 2007 Jun;192(2):298-304. doi: 
      10.1016/j.atherosclerosis.2006.07.023. Epub 2006 Sep 26.