TY - JOUR
TI - Orexin-a exerts equivocal role in atherosclerosis process depending on the duration of exposure: In vitro study
AU - Ansari, N.N.
AU - Spentza, F.
AU - Dimitriadis, G.K.
AU - Daskalopoulou, A.
AU - Karapanagioti, A.
AU - Siasos, G.
AU - Lianidou, E.
AU - Papavassiliou, A.G.
AU - Kassi, E.
AU - Randeva, H.S.
JO - Nutrient Cycling in Agroecosystems
PY - 2020
VL - 12
TODO - 1
SP - null
PB - MDPI AG
SN - 1385-1314
TODO - 10.3390/nu12010053
TODO - gelatin;  gelatinase A;  gelatinase B;  heme oxygenase 1;  matrix metalloproteinase;  messenger RNA;  monocyte chemotactic protein 1;  orexin A;  synaptophysin;  tissue inhibitor of metalloproteinase 1;  tissue inhibitor of metalloproteinase 2;  transcription factor RelA, aortic endothelial cell;  Article;  atherogenesis;  atherosclerosis;  cell culture;  cell proliferation assay;  cell signaling assay;  cell viability assay;  controlled study;  drug exposure;  endothelium cell;  enzyme activity;  enzyme linked immunosorbent assay;  feeding behavior;  homeostasis;  human;  human cell;  in vitro study;  incubation time;  MTS assay;  polymerase chain reaction;  protein expression;  protein phosphorylation;  real time polymerase chain reaction;  signal transduction;  treatment duration;  Western blotting;  zymography
TODO - 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-κB/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-κB pathway. Orexin-A may have an equivocal role in atherosclerosis process with its effects depending on the duration of exposure. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
ER -