PMID- 31878149
OWN - NLM
STAT- MEDLINE
DCOM- 20200826
LR  - 20200826
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 12
IP  - 1
DP  - 2019 Dec 24
TI  - Orexin-A Exerts Equivocal Role in Atherosclerosis Process Depending on the 
      Duration of Exposure: In Vitro Study.
LID - 10.3390/nu12010053 [doi]
LID - 53
AB  - Orexin-A is a peptide hormone that plays a crucial role in feeding regulation and 
      energy homeostasis. Diurnal intermittent fasting (DIF) has been found to increase 
      orexin-A plasma levels during fasting hours, while Ramadan fasting which 
      resembles DIF, has led to beneficial effects on endothelial function. Herein, we 
      aimed to investigate the effects of orexin-A on the expression of molecules 
      involved in the atherogenesis process: Monocyte chemoattractant protein-1 
      (MCP-1), matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and tissue inhibitor 
      of metalloproteinase-1 and 2 (TIMP-1 and TIMP-2), in human aortic endothelial 
      cells (HAECs). HAECs were incubated with orexin-A at concentrations of 40 ng/mL, 
      200 ng/mL and 400 ng/mL for 6, 12 and 24 h. The mRNA levels of MCP-1, MMP-2, 
      MMP-9, TIMP-1, and TIMP-2 and orexin-1 receptor were measured by real-time qPCR. 
      We also evaluated the MMP-2, p38, phospho-p38, NF-kappaBeta/p65 as well as TIMP-1 
      protein levels by Western blot and ELISA, respectively. MMP-2 activity was 
      measured by gelatin zymography. Short-term 6-h incubation of HAECs with orexin-A 
      at a high concentration (400 ng/mL) decreased MCP-1, MMP-2 expression, 
      MMP-2/TIMP-1 ratio (p < 0.05), and MMP-2 activity, while incubation for 24 h 
      increased MCP-1, MMP-2 expression (p < 0.05), MMP-2/TIMP-1 and MMP-2/TIMP-2 ratio 
      (p < 0.01 and p < 0.05, respectively) as well as MMP-2 activity. The dual effects 
      of orexin-A are mediated, at least in part, via regulation of p38 and NF-kappaBeta 
      pathway. Orexin-A may have an equivocal role in atherosclerosis process with its 
      effects depending on the duration of exposure.
FAU - Nasiri Ansari, Narjes
AU  - Nasiri Ansari N
AUID- ORCID: 0000-0002-0116-693X
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
FAU - Spentza, Flora
AU  - Spentza F
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
FAU - Dimitriadis, Georgios K
AU  - Dimitriadis GK
AUID- ORCID: 0000-0002-6662-804X
AD  - Department of Endocrinology, King's College Hospital NHS Foundation Trust, 
      Denmark Hill, London SE5 9RS, UK.
FAU - Daskalopoulou, Aphrodite
AU  - Daskalopoulou A
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
FAU - Karapanagioti, Angeliki
AU  - Karapanagioti A
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
FAU - Siasos, Gerasimos
AU  - Siasos G
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
AD  - 1st Department of Cardiology, Hippokration Hospital, National and Kapodistrian 
      University of Athens, Medical School, 11527 Athens, Greece.
FAU - Lianidou, Evi
AU  - Lianidou E
AD  - Department of Chemistry, Analysis of Circulating Tumor Cells Lab, Laboratory of 
      Analytical Chemistry, University of Athens, 15784 Athens, Greece.
FAU - Papavassiliou, Athanasios G
AU  - Papavassiliou AG
AUID- ORCID: 0000-0001-5803-4527
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
FAU - Kassi, Eva
AU  - Kassi E
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
FAU - Randeva, Harpal S
AU  - Randeva HS
AD  - Division of Translational and Experimental Medicine-Metabolic and Vascular 
      Health, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
AD  - Human Metabolism Research Unit, WISDEM Centre, University Hospitals Coventry and 
      Warwickshire NHS Trust, Coventry CV2 2DX, UK.
LA  - eng
PT  - Journal Article
DEP - 20191224
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Orexins)
RN  - 0 (TIMP1 protein, human)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Atherosclerosis/*prevention & control
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Chemokine CCL2/genetics/metabolism
MH  - Drug Administration Schedule
MH  - Endothelial Cells/*drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Matrix Metalloproteinase 2/genetics/metabolism
MH  - Orexins/administration & dosage/*pharmacology
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics/metabolism
PMC - PMC7019720
OTO - NOTNLM
OT  - MCP-1
OT  - MMPs
OT  - atherosclerosis
OT  - breast feeding
OT  - diurnal intermittent fasting
OT  - endothelial cells
OT  - orexin-alpha
COIS- The authors declare that they have no competing interests.
EDAT- 2019/12/28 06:00
MHDA- 2020/08/28 06:00
PMCR- 2020/01/01
CRDT- 2019/12/28 06:00
PHST- 2019/12/02 00:00 [received]
PHST- 2019/12/17 00:00 [accepted]
PHST- 2019/12/28 06:00 [entrez]
PHST- 2019/12/28 06:00 [pubmed]
PHST- 2020/08/28 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - nu12010053 [pii]
AID - nutrients-12-00053 [pii]
AID - 10.3390/nu12010053 [doi]
PST - epublish
SO  - Nutrients. 2019 Dec 24;12(1):53. doi: 10.3390/nu12010053.