PMID- 30393020
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20220208
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 214
DP  - 2018 Dec 1
TI  - Homocysteine accelerates atherosclerosis via inhibiting LXRalpha-mediated 
      ABCA1/ABCG1-dependent cholesterol efflux from macrophages.
PG  - 41-50
LID - S0024-3205(18)30690-8 [pii]
LID - 10.1016/j.lfs.2018.10.060 [doi]
AB  - AIMS: Macrophage-derived foam-cell formation plays a crucial role in the 
      development of atherosclerosis, and liver X receptor alpha (LXRalpha) is a key 
      regulator of lipid metabolism in macrophages. Homocysteine (Hcy) is an 
      independent risk factor of atherosclerosis; however, the regulation of lipid 
      metabolism and role of LXRalpha induced by Hcy in macrophages is still unknown. The 
      present study aimed to investigate the potential role of Hcy in disordered lipid 
      metabolism and atherosclerotic lesions, especially the effects of Hcy on 
      cholesterol efflux in macrophages and the possible mechanisms. MAIN METHODS: In 
      vitro, lipid accumulation and cholesterol efflux were evaluated in THP-1 
      macrophages with Hcy intervention. Real-time quantitative PCR and western blot 
      analyses were used to assess mRNA and protein levels. In vivo, atherosclerotic 
      lesions and lipid profiles were evaluated by methionine diet-induced 
      hyperhomocysteinemia (HHcy) in ApoE(-/-) mice. The LXRalpha agonist T0901317 was used 
      to verify the role of LXRalpha in HHcy-accelerated atherosclerosis. KEY FINDINGS: Hcy 
      promoted lipid accumulation and inhibited cholesterol efflux in THP-1 
      macrophages. HHcy mice showed increased lesion area and lipid accumulation in 
      plaque. Both studies in vitro and in vivo showed decreased expression of ATP 
      binding cassette transporter A1 (ABCA1) and G1 (ABCG1). T0901317 treatment 
      increased ABCA1 and ABCG1 levels; reversed macrophage-derived foam-cell formation 
      in THP-1 macrophages and reduced atherosclerotic lesions in ApoE(-/-) mice. 
      SIGNIFICANCE: Inhibition of LXRalpha-mediated ABCA1/ABCG1-dependent cholesterol 
      efflux from macrophages is a novel mechanism in Hcy-accelerated atherosclerosis.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Jin, Ping
AU  - Jin P
AD  - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 
      750001, China.
FAU - Bian, Yitong
AU  - Bian Y
AD  - Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi 710061, China.
FAU - Wang, Kai
AU  - Wang K
AD  - Heart Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 
      750001, China.
FAU - Cong, Guangzhi
AU  - Cong G
AD  - Heart Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 
      750001, China.
FAU - Yan, Ru
AU  - Yan R
AD  - Institute of Cardiovascular Diseases, General Hospital of Ningxia Medical 
      University Yinchuan, Ningxia 750001, China.
FAU - Sha, Yong
AU  - Sha Y
AD  - Heart Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 
      750001, China.
FAU - Ma, Xueping
AU  - Ma X
AD  - Heart Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 
      750001, China.
FAU - Zhou, Juan
AU  - Zhou J
AD  - Department of Cardiovascular Medicine, The First Affiliated Hospital of the 
      Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
FAU - Yuan, Zuyi
AU  - Yuan Z
AD  - Department of Cardiovascular Medicine, The First Affiliated Hospital of the 
      Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
FAU - Jia, Shaobin
AU  - Jia S
AD  - Heart Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 
      750001, China; Institute of Cardiovascular Diseases, General Hospital of Ningxia 
      Medical University Yinchuan, Ningxia 750001, China. Electronic address: 
      jsbxn@163.com.
LA  - eng
PT  - Journal Article
DEP - 20181028
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (ABCA1 protein, human)
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Liver X Receptors)
RN  - 0 (NR1H3 protein, human)
RN  - 0 (Sulfonamides)
RN  - 0 (T0901317)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/*metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1/*metabolism
MH  - Animals
MH  - Atherosclerosis/*metabolism/pathology
MH  - Cell Line
MH  - Cholesterol/metabolism
MH  - Foam Cells/metabolism/pathology
MH  - Homocysteine/blood/*metabolism
MH  - Humans
MH  - Hydrocarbons, Fluorinated/pharmacology
MH  - Lipid Metabolism
MH  - Liver X Receptors/agonists/metabolism
MH  - Macrophages/*metabolism/pathology
MH  - Male
MH  - Mice, Knockout, ApoE
MH  - Plaque, Atherosclerotic/drug therapy/metabolism/pathology
MH  - Sulfonamides/pharmacology
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Cholesterol efflux
OT  - Homocysteine
OT  - LXRalpha
OT  - Macrophages
EDAT- 2018/11/06 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/11/06 06:00
PHST- 2018/08/18 00:00 [received]
PHST- 2018/10/15 00:00 [revised]
PHST- 2018/10/26 00:00 [accepted]
PHST- 2018/11/06 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/11/06 06:00 [entrez]
AID - S0024-3205(18)30690-8 [pii]
AID - 10.1016/j.lfs.2018.10.060 [doi]
PST - ppublish
SO  - Life Sci. 2018 Dec 1;214:41-50. doi: 10.1016/j.lfs.2018.10.060. Epub 2018 Oct 28.