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Open AccessArticle

Orexin-A Exerts Equivocal Role in Atherosclerosis Process Depending on the Duration of Exposure: In Vitro Study

1
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
2
Department of Endocrinology, King’s College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK
3
1st Department of Cardiology, Hippokration Hospital, National and Kapodistrian University of Athens, Medical School, 11527 Athens, Greece
4
Department of Chemistry, Analysis of Circulating Tumor Cells Lab, Laboratory of Analytical Chemistry, University of Athens, 15784 Athens, Greece
5
Division of Translational and Experimental Medicine-Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
6
Human Metabolism Research Unit, WISDEM Centre, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
*
Authors to whom correspondence should be addressed.
N.N.A. and F.S. are joint first authors.
E.K. and H.S.R. are joint last and corresponding authors.
Nutrients 2020, 12(1), 53; https://doi.org/10.3390/nu12010053
Received: 2 December 2019 / Accepted: 17 December 2019 / Published: 24 December 2019
(This article belongs to the Special Issue Dietary Supplementation and Vascular Function)
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-κΒ/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-κΒ pathway. Orexin-A may have an equivocal role in atherosclerosis process with its effects depending on the duration of exposure. View Full-Text
Keywords: atherosclerosis; endothelial cells; orexin-α; MMPs; MCP-1; breast feeding; diurnal intermittent fasting atherosclerosis; endothelial cells; orexin-α; MMPs; MCP-1; breast feeding; diurnal intermittent fasting
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Nasiri Ansari, N.; Spentza, F.; Dimitriadis, G.K.; Daskalopoulou, A.; Karapanagioti, A.; Siasos, G.; Lianidou, E.; Papavassiliou, A.G.; Kassi, E.; Randeva, H.S. Orexin-A Exerts Equivocal Role in Atherosclerosis Process Depending on the Duration of Exposure: In Vitro Study. Nutrients 2020, 12, 53.

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