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Recombinant Human Cytoglobin Prevents Atherosclerosis by Regulating Lipid Metabolism and Oxidative Stress
Ist Teil von
Journal of cardiovascular pharmacology and therapeutics, 2018-03, Vol.23 (2), p.162-173
Ort / Verlag
Los Angeles, CA: SAGE Publications
Erscheinungsjahr
2018
Quelle
MEDLINE
Beschreibungen/Notizen
Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid
accumulation and endothelial dysfunction. Cytoglobin has been shown to exert protective
effects under oxidative stress conditions. The aim of this study was to determine whether
recombinant human cytoglobin (rhCYGB) has protective effects against atherosclerosis. We
intraperitoneally injected rhCYGB (0, 4, or 7 mg/kg BW) into the atherosclerotic rats
daily for 60 days. The rhCYGB injections reduced low-density lipoprotein cholesterol
(LDL-C) levels and increased high-density lipoprotein cholesterol levels in a
dose-dependent manner, rhCYGB (7 mg/kg) significantly attenuated atherosclerosis. Blood
proteins were separated by 2-dimensional electrophoresis and analyzed by mass
spectrometry, and the majority of the proteins in question were participated in oxidative
stress pathways and cardiovascular diseases. Human hepatocellular liver carcinoma cell
line (HepG2) cells were treated with oleic acid (0.3 mmol/L), and Human acute monocytic
leukemia cell line (THP-1) cells were incubated with oxidized LDL (ox-LDL; 50 µg/mL) to
induce foam cell (FC) formation in vitro. Treatment with different concentrations of
rhCYGB (0, 5, 10, and 15 μg/mL) significantly decreased the lipid droplet levels in HepG2
cells and cholesterol ester levels in FCs. Moreover, rhCYGB significantly increased
superoxide dismutase and glutathione peroxidase activity and decreased malondialdehyde and
nicotinamide adenine dinucleotide phosphate oxidase activity in cells. In addition, rhCYGB
decreased NO and Reactive oxygen species (ROS) levels in FCs by functioning as an NO
dioxygenase enzyme and ROS scavenger. Taken together, our findings indicate that rhCYGB
prevented atherosclerosis by regulating lipid metabolism and oxidative stress. Our study
provides insights into the possible usefulness of rhCYGB as an antiatherosclerosis
agent.