PMID- 24980430
OWN - NLM
STAT- MEDLINE
DCOM- 20151028
LR  - 20220311
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 4
DP  - 2014 Jul 1
TI  - An activator of mTOR inhibits oxLDL-induced autophagy and apoptosis in vascular 
      endothelial cells and restricts atherosclerosis in apolipoprotein E(-)/(-) mice.
PG  - 5519
LID - 10.1038/srep05519 [doi]
LID - 5519
AB  - Oxidized low-density lipoprotein (oxLDL) inhibits mammalian target of rapamycin 
      (mTOR) and induces autophagy and apoptosis in vascular endothelial cells (VECs) 
      that play very critical roles for the cardiovascular homostasis. We recently 
      defined 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) as a 
      new activator of mTOR. Therefore, we hypothesized that 3BDO had a protective role 
      in VECs and thus stabilized atherosclerotic lesions in apolipoprotein E(-/-) 
      (apoE(-/-)) mice. Our results showed that oxLDL inhibited the activity of mTOR 
      and increased the protein level of autophagy-related 13 (ATG13) and its 
      dephosphorylation, thus inducing autophagy in human umbilical vein endothelial 
      cells (HUVECs). All of these effects were strongly inhibited by 3BDO. In vivo 
      experiments confirmed that 3BDO activated mTOR and decreased the protein level of 
      ATG13 in the plaque endothelium of apoE(-/-) mice. Importantly, 3BDO did not 
      affect the activity of mTOR and autophagy in macrophage cell line RAW246.7 and 
      vascular smooth muscle cells of apoE(-/-) mice, but suppressed plaque endothelial 
      cell death and restricted atherosclerosis development in the mice. 3BDO protected 
      VECs by activating mTOR and thus stabilized atherosclerotic lesions in apoE(-/-) 
      mice.
FAU - Peng, Nan
AU  - Peng N
AD  - 1] Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Science, Shandong University, Jinan 250100, China [2].
FAU - Meng, Ning
AU  - Meng N
AD  - 1] School of Biological Science and Technology, University of Jinan, Jinan 
      250022, China [2] Institute of Organic Chemistry, School of Chemistry and 
      Chemical Engineering, Shandong University, Jinan 250100, China [3].
FAU - Wang, ShengQing
AU  - Wang S
AD  - Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, 
      Shandong University, Jinan 250100, China.
FAU - Zhao, Fei
AU  - Zhao F
AD  - Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Science, Shandong University, Jinan 250100, China.
FAU - Zhao, Jing
AU  - Zhao J
AD  - Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Science, Shandong University, Jinan 250100, China.
FAU - Su, Le
AU  - Su L
AD  - Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Science, Shandong University, Jinan 250100, China.
FAU - Zhang, ShangLi
AU  - Zhang S
AD  - Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Science, Shandong University, Jinan 250100, China.
FAU - Zhang, Yun
AU  - Zhang Y
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education and Chinese Ministry of Health, Shandong University Qilu 
      Hospital, Jinan, 250012, China.
FAU - Zhao, BaoXiang
AU  - Zhao B
AD  - Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, 
      Shandong University, Jinan 250100, China.
FAU - Miao, JunYing
AU  - Miao J
AD  - 1] Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, 
      School of Life Science, Shandong University, Jinan 250100, China [2] The Key 
      Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry 
      of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 
      Jinan, 250012, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140701
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (3-benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3H)-one)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - OL659KIY4X (4-Butyrolactone)
SB  - IM
MH  - 4-Butyrolactone/administration & dosage/*analogs & derivatives
MH  - Animals
MH  - Apolipoproteins E/genetics/metabolism
MH  - Atherosclerosis/*metabolism/*prevention & control
MH  - Autophagy
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/cytology/drug effects/*metabolism
MH  - Lipoproteins, LDL/*administration & dosage
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Treatment Outcome
PMC - PMC4076681
EDAT- 2014/07/02 06:00
MHDA- 2015/10/29 06:00
PMCR- 2014/07/01
CRDT- 2014/07/02 06:00
PHST- 2014/03/31 00:00 [received]
PHST- 2014/06/13 00:00 [accepted]
PHST- 2014/07/02 06:00 [entrez]
PHST- 2014/07/02 06:00 [pubmed]
PHST- 2015/10/29 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - srep05519 [pii]
AID - 10.1038/srep05519 [doi]
PST - epublish
SO  - Sci Rep. 2014 Jul 1;4:5519. doi: 10.1038/srep05519.