PMID- 30124738
OWN - NLM
STAT- MEDLINE
DCOM- 20181217
LR  - 20181217
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Linking)
VI  - 50
IP  - 9
DP  - 2018 Sep 1
TI  - Circadian locomotor output cycles kaput accelerates atherosclerotic plaque 
      formation by upregulating plasminogen activator inhibitor-1 expression.
PG  - 869-879
LID - 10.1093/abbs/gmy087 [doi]
AB  - To explore the association between clock circadian regulator circadian locomotor 
      output cycles kaput gene (CLOCK) and the forming of atherosclerotic plaques and 
      its underlying mechanisms, mouse aortic endothelial cells (MAECs) and 
      atherosclerosis (AS) mouse model were recruited for our study. The apoE gene 
      knockout mouse was used as the model of AS and we accelerated the formation of 
      unstable plaques through the combination of carotid artery ligation and high-fat 
      (HF) diet administration (0.2% cholesterol, 20% fat). The mRNA and protein 
      expressions of CLOCK in peripheral blood monouclear cells of acute coronary 
      syndrome (ACS) patients or mouse AS model were detected by qPCR, western blot 
      analysis and immunohistochemical staining. The number of adherent cells and 
      atherosclerotic plaques was counted to assess the effects of CLOCK on the 
      progression of ACS, and adherence-associated genes, such as vascular cell 
      adhesion molecule (VCAM)-1, C-C motif chemokine ligand 2 (CCL-2), and CCL-5. The 
      results showed that CLOCK expression was significantly increased in both ACS 
      patients and AS mouse model. The levels of CLOCK, leukemia inhibitory factor 
      (LIF), intercellular adhesion molecule 1 (ICAM-1), perilipin 2 (ADFP), nuclear 
      factor kappa B (NF-kappaB), and plasminogen activator inhibitor-1 (PAI-1), as well as 
      the number of atherosclerotic plaques were elevated in the AS mouse model, as 
      compared with the control group. Chromatin immunoprecipitation assay showed that 
      CLOCK bound directly to the promoter of PAI-1 gene and CLOCK could positively 
      regulate the expressions of LIF, ICAM-1, ADFP, NF-kappaB, and PAI-1. Reduction of 
      CLOCK expression would decrease the expressions of VCAM-1, CCL-2, and CCL-5, and 
      the number of adherent cells and atherosclerotic plaques, but these effects were 
      neutralized when PAI-1 was simultaneously overexpressed in either mouse model or 
      MAECs. Our results demonstrate that CLOCK overexpression triggers the formation 
      of atherosclerotic plaques by directly upregulating PAI-1 expression.
FAU - Jiang, Qixia
AU  - Jiang Q
AD  - Department of Cardiology, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Liu, Hua
AU  - Liu H
AD  - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, 
      Shanghai, China.
FAU - Wang, Shengyun
AU  - Wang S
AD  - Department of Emergency and Critical Care Medicine, Changzheng Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Wang, Jiamei
AU  - Wang J
AD  - Department of Cardiology, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Tang, Yehua
AU  - Tang Y
AD  - Department of Cardiology, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - He, Zhiqing
AU  - He Z
AD  - Department of Cardiology, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Wu, Feng
AU  - Wu F
AD  - Department of Cardiology, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Huang, Zhigang
AU  - Huang Z
AD  - Department of Cardiology, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Cong, Xiaoliang
AU  - Cong X
AD  - Department of Cardiology, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Ding, Ru
AU  - Ding R
AD  - Department of Cardiology, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Liang, Chun
AU  - Liang C
AD  - Department of Cardiology, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 0 (Apolipoproteins E)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - EC 2.3.1.48 (CLOCK Proteins)
SB  - IM
MH  - Acute Coronary Syndrome/*genetics/metabolism/pathology
MH  - Aged
MH  - Animals
MH  - Apolipoproteins E/genetics/metabolism
MH  - CLOCK Proteins/*genetics/metabolism
MH  - Cells, Cultured
MH  - Diet, High-Fat/adverse effects
MH  - Endothelial Cells/metabolism
MH  - Humans
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Plaque, Atherosclerotic/etiology/*genetics/metabolism
MH  - Plasminogen Activator Inhibitor 1/*genetics/metabolism
MH  - RNA Interference
MH  - Up-Regulation/*genetics
EDAT- 2018/08/21 06:00
MHDA- 2018/12/18 06:00
CRDT- 2018/08/21 06:00
PHST- 2017/11/07 00:00 [received]
PHST- 2018/08/21 06:00 [pubmed]
PHST- 2018/12/18 06:00 [medline]
PHST- 2018/08/21 06:00 [entrez]
AID - 5073300 [pii]
AID - 10.1093/abbs/gmy087 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2018 Sep 1;50(9):869-879. doi: 
      10.1093/abbs/gmy087.