PMID- 32001235
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20200831
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 174
DP  - 2020 Apr
TI  - Omentin-1 protects against high glucose-induced endothelial dysfunction via the 
      AMPK/PPARdelta signaling pathway.
PG  - 113830
LID - S0006-2952(20)30040-X [pii]
LID - 10.1016/j.bcp.2020.113830 [doi]
AB  - High glucose-induced endothelial dysfunction is a critical initiating factor in 
      the development of diabetic vascular complications. Omentin-1 has been regarded 
      as a novel biomarker of endothelial function in subjects with type-2 diabetes 
      (T2D); however, it is unclear whether omentin-1 has any direct effect in 
      ameliorating high glucose-induced endothelial dysfunction. In the present study, 
      we analyzed the effect of omentin-1 on high glucose-induced endothelial 
      dysfunction in isolated mouse aortas and mouse aortic endothelial cells (MAECs). 
      Vascular reactivity in aortas was measured using wire myography. The expression 
      levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated 
      receptor delta (PPARdelta), Akt, endothelial nitric-oxide synthase (eNOS), and 
      endoplasmic reticulum (ER)-stress markers in MAECs were determined by Western 
      blotting. The production of reactive oxygen species (ROS) and nitric oxide (NO) 
      was assessed by diluted fluoroprobe, 2',7'-dichlorodihydrofluorescein diacetate 
      (DCFH-DA) and 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM DA), 
      respectively. We found that ex vivo treatment with omentin-1 reversed impaired 
      endothelial-dependent relaxations (EDR) in mouse aortas after high-glucose 
      insult. Elevated ER-stress markers, oxidative stress, and reduction of NO 
      production induced by high glucose in MAECs were reversed by omentin-1 treatment. 
      Omentin-1 also effectively reversed tunicamycin-induced ER stress responses in 
      MAECs, as well as ameliorated impairment of endothelial-dependent relaxation in 
      mouse aortas. Moreover, omentin-1 increased AMPK phosphorylation with a 
      subsequent increase in PPARdelta expression, while also restoring the decreased 
      phosphorylation of Akt and eNOS. The effects of omentin-1 were abolished by 
      cotreatment of compound C (AMPK inhibitor) and GSK0660 (PPARdelta antagonist). These 
      data indicate that omentin-1 protects against high glucose-induced 
      vascular-endothelial dysfunction through inhibiting ER stress and oxidative 
      stress and increasing NO production via activation of AMPK/PPARdelta pathway.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Liu, Fang
AU  - Liu F
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China; Department of Cardiology, The Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China.
FAU - Fang, Shaohong
AU  - Fang S
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China.
FAU - Liu, Xinxin
AU  - Liu X
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China; Department of Cardiology, The Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China.
FAU - Li, Ji
AU  - Li J
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China.
FAU - Wang, Xuedong
AU  - Wang X
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China; Department of Cardiology, The Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China.
FAU - Cui, Jinjin
AU  - Cui J
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China; Department of Cardiology, The Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China.
FAU - Chen, Tao
AU  - Chen T
AD  - Department of Cardiology, The Second Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Li, Zhaoying
AU  - Li Z
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China.
FAU - Yang, Fan
AU  - Yang F
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China.
FAU - Tian, Jiangtian
AU  - Tian J
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China.
FAU - Li, Hulun
AU  - Li H
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China.
FAU - Yin, Li
AU  - Yin L
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China; Department of Cardiology, The Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China. Electronic address: 
      yinli@hrbmu.edu.cn.
FAU - Yu, Bo
AU  - Yu B
AD  - The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of 
      Education, Harbin, China; Department of Cardiology, The Second Affiliated 
      Hospital of Harbin Medical University, Harbin, China. Electronic address: 
      yubo@hrbmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200128
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Cytokines)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Itln1 protein, mouse)
RN  - 0 (Lectins)
RN  - 0 (PPAR delta)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Cytokines/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/drug effects/*metabolism
MH  - GPI-Linked Proteins/*pharmacology
MH  - Glucose/*toxicity
MH  - Lectins/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Organ Culture Techniques
MH  - PPAR delta/*metabolism
MH  - Signal Transduction/drug effects/*physiology
OTO - NOTNLM
OT  - AMP-activated protein kinase
OT  - Endothelial dysfunction
OT  - High glucose
OT  - Omentin-1
OT  - Peroxisome proliferator-activated receptor delta
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/02/01 06:00
MHDA- 2020/09/01 06:00
CRDT- 2020/02/01 06:00
PHST- 2019/09/02 00:00 [received]
PHST- 2020/01/24 00:00 [accepted]
PHST- 2020/02/01 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2020/02/01 06:00 [entrez]
AID - S0006-2952(20)30040-X [pii]
AID - 10.1016/j.bcp.2020.113830 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2020 Apr;174:113830. doi: 10.1016/j.bcp.2020.113830. Epub 2020 
      Jan 28.