Plasma APE1/Ref-1 Correlates with Atherosclerotic Inflammation in ApoE−/− Mice
Open Access
- 21 September 2020
- journal article
- research article
- Published by MDPI AG in Biomedicines
- Vol. 8 (9), 366
- https://doi.org/10.3390/biomedicines8090366
Abstract
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is involved in DNA base repair and reducing activity. However, the role of APE1/Ref-1 in atherosclerosis is unclear. Herein, we investigated the role of APE1/Ref-1 in atherosclerotic apolipoprotein E (ApoE−/−) mice fed with a Western-type diet. We found that serologic APE1/Ref-1 was strongly correlated with vascular inflammation in these mice. Neutrophil/lymphocyte ratio (NLR), endothelial cell/macrophage activation, and atherosclerotic plaque formation, reflected by atherosclerotic inflammation, were increased in the ApoE−/− mice fed with a Western-type diet. APE1/Ref-1 expression was upregulated in aortic tissues of these mice, and was co-localized with cells positive for cluster of differentiation 31 (CD31) and galectin-3, suggesting endothelial cell/macrophage expression of APE1/Ref-1. Interestingly, APE1/Ref-1 plasma levels of ApoE−/− mice fed with a Western-type diet were significantly increased compared with those of the mice fed with normal diet (15.76 ± 3.19 ng/mL vs. 3.51 ± 0.50 ng/mL, p < 0.05), and were suppressed by atorvastatin administration. Correlation analysis showed high correlation between plasma APE1/Ref-1 levels and NLR, a marker of systemic inflammation. The cut-off value for APE1/Ref-1 for predicting atherosclerotic inflammation at 4.903 ng/mL showed sensitivity of 100% and specificity of 91%. We conclude that APE1/Ref-1 expression is upregulated in aortic endothelial cells/macrophages of atherosclerotic mice, and that plasma APE1/Ref-1 levels could predict atherosclerotic inflammation.Keywords
Funding Information
- National Research Foundation of Korea (2020R1C1C1014490, 2017R1A6A3A11027834, 2014R1A6A1029617)
This publication has 59 references indexed in Scilit:
- DNA Damage and Repair in Atherosclerosis: Current Insights and Future PerspectivesInternational Journal of Molecular Sciences, 2012
- Redox Regulating Protein APE1/Ref-1 Expression is Increased in Abdominal Aortic Coarctation-induced Hypertension RatsJournal of the Korean Society of Hypertension, 2012
- Apurinic/apyrimidinic endonuclease 1 inhibits protein kinase C-mediated p66shc phosphorylation and vasoconstrictionCardiovascular Research, 2011
- The Many Functions of APE1/Ref-1: Not Only a DNA Repair EnzymeAntioxidants and Redox Signaling, 2009
- Decreased levels of lipid peroxidation-induced DNA damage in the onset of atherogenesis in apolipoprotein E deficient miceMutation Research, 2007
- Apurinic/apyrimidinic endonuclease1/redox factor-1 inhibits monocyte adhesion in endothelial cellsCardiovascular Research, 2006
- Apurinic/Apyrmidinic Endonuclease 1 Regulates Endothelial NO Production and Vascular ToneCirculation Research, 2004
- Inflammation in atherosclerosisNature, 2002
- Transcriptional Activation of Apurinic/Apyrimidinic Endonuclease (Ape, Ref-1) by Oxidative Stress Requires CREBBiochemical and Biophysical Research Communications, 1999
- Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cellsCell, 1992