PMID- 26288135
OWN - NLM
STAT- MEDLINE
DCOM- 20160524
LR  - 20201215
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 8
DP  - 2015
TI  - LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and 
      PRMT2.
PG  - e0135218
LID - 10.1371/journal.pone.0135218 [doi]
LID - e0135218
AB  - High cholesterol and diabetes are major risk factors for atherosclerosis. 
      Regression of atherosclerosis is mediated in part by the Liver X Receptor (LXR) 
      through the induction of genes involved in cholesterol transport and efflux. In 
      the context of diabetes, regression of atherosclerosis is impaired. We proposed 
      that changes in glucose levels modulate LXR-dependent gene expression. Using a 
      mouse macrophage cell line (RAW 264.7) and primary bone marrow derived 
      macrophages (BMDMs) cultured in normal or diabetes relevant high glucose 
      conditions we found that high glucose inhibits the LXR-dependent expression of 
      ATP-binding cassette transporter A1 (ABCA1), but not ABCG1. To probe for this 
      mechanism, we surveyed the expression of a host of chromatin-modifying enzymes 
      and found that Protein Arginine Methyltransferase 2 (PRMT2) was reduced in high 
      compared to normal glucose conditions. Importantly, ABCA1 expression and 
      ABCA1-mediated cholesterol efflux were reduced in Prmt2-/- compared to wild type 
      BMDMs. Monocytes from diabetic mice also showed decreased expression of Prmt2 
      compared to non-diabetic counterparts. Thus, PRMT2 represents a glucose-sensitive 
      factor that plays a role in LXR-mediated ABCA1-dependent cholesterol efflux and 
      lends insight to the presence of increased atherosclerosis in diabetic patients.
FAU - Hussein, Maryem A
AU  - Hussein MA
AD  - Department of Microbiology, NYU School of Medicine, New York, New York, United 
      States of America.
FAU - Shrestha, Elina
AU  - Shrestha E
AD  - Department of Microbiology, NYU School of Medicine, New York, New York, United 
      States of America.
FAU - Ouimet, Mireille
AU  - Ouimet M
AD  - Department of Medicine, NYU School of Medicine, New York, New York, United States 
      of America.
FAU - Barrett, Tessa J
AU  - Barrett TJ
AD  - Department of Medicine, NYU School of Medicine, New York, New York, United States 
      of America.
FAU - Leone, Sarah
AU  - Leone S
AD  - Department of Microbiology, NYU School of Medicine, New York, New York, United 
      States of America.
FAU - Moore, Kathryn J
AU  - Moore KJ
AD  - Department of Medicine, NYU School of Medicine, New York, New York, United States 
      of America.
FAU - Herault, Yann
AU  - Herault Y
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire, Illkirch, 1 rue 
      Laurent Fries, 67404, Illkirch, France; Centre National de la Recherche 
      Scientifique, UMR7104, Illkirch, France; Institut National de la Sante et de la 
      Recherche Medicale, U964, Illkirch, France; Universite de Strasbourg, Illkirch, 
      France; Institut Clinique de la Souris, ICS, 1 rue Laurent Fries, 67404, 
      Illkirch, France.
FAU - Fisher, Edward A
AU  - Fisher EA
AD  - Department of Medicine, NYU School of Medicine, New York, New York, United States 
      of America.
FAU - Garabedian, Michael J
AU  - Garabedian MJ
AD  - Department of Microbiology, NYU School of Medicine, New York, New York, United 
      States of America.
LA  - eng
GR  - R01 HL117226/HL/NHLBI NIH HHS/United States
GR  - T32 GM007238/GM/NIGMS NIH HHS/United States
GR  - T32GM007238/GM/NIGMS NIH HHS/United States
GR  - T32AI07180/AI/NIAID NIH HHS/United States
GR  - R01 DK095684/DK/NIDDK NIH HHS/United States
GR  - R01DK095684/DK/NIDDK NIH HHS/United States
GR  - T32 GM007308/GM/NIGMS NIH HHS/United States
GR  - T32 AI007180/AI/NIAID NIH HHS/United States
GR  - R01HL117226/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150819
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (ABCA1 protein, mouse)
RN  - 0 (ABCG1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Blood Glucose)
RN  - 0 (Lipoproteins)
RN  - 0 (Liver X Receptors)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.319 (PRMT2 protein, mouse)
RN  - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/biosynthesis/*metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/biosynthesis/metabolism
MH  - Animals
MH  - Atherosclerosis/pathology
MH  - Biological Transport/genetics
MH  - Blood Glucose/*analysis
MH  - Cell Line
MH  - Cholesterol/blood/metabolism
MH  - Diabetes Mellitus, Experimental
MH  - Hypercholesterolemia/*blood
MH  - Lipoproteins/biosynthesis/metabolism
MH  - Liver X Receptors
MH  - Macrophages/metabolism
MH  - Male
MH  - Methyltransferases/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Orphan Nuclear Receptors/biosynthesis/*metabolism
MH  - Protein-Arginine N-Methyltransferases
PMC - PMC4545936
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/08/20 06:00
MHDA- 2016/05/25 06:00
PMCR- 2015/08/19
CRDT- 2015/08/20 06:00
PHST- 2015/05/08 00:00 [received]
PHST- 2015/07/20 00:00 [accepted]
PHST- 2015/08/20 06:00 [entrez]
PHST- 2015/08/20 06:00 [pubmed]
PHST- 2016/05/25 06:00 [medline]
PHST- 2015/08/19 00:00 [pmc-release]
AID - PONE-D-15-19743 [pii]
AID - 10.1371/journal.pone.0135218 [doi]
PST - epublish
SO  - PLoS One. 2015 Aug 19;10(8):e0135218. doi: 10.1371/journal.pone.0135218. 
      eCollection 2015.