Elevation of the Serum Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 in Coronary Artery Disease

Background and Objectives: Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a multifunctional protein involved in the DNA base excision repair pathway, inflammation, angiogenesis, and survival pathways. We investigated serum APE1/Ref-1 in patients with coronary artery disease (CAD). Subjects and Methods: Serum APE1/Ref-1 was measured with a sandwich enzyme-linked immunosorbent assay from 360 patients who received coronary angiograms. They were divided into two groups; a control (n=57) and a CAD group (n=303), the latter included angina (n=128) and myocardial infarction (MI, n=175). Results: The levels of APE1/Ref-1 were higher in the CAD than the control ($0.63{\pm}0.07$ vs. $0.12{\pm}0.07ng/100{\mu}L$, respectively; p<0.01). They were also higher in MI than angina ($0.81{\pm}0.10$ vs. $0.38{\pm}0.11ng/100{\mu}L$ L, respectively; p<0.01) and different according to the thrombolysis in myocardial infarction (TIMI) flow ($0.88{\pm}0.09$ for TIMI flow 0, 1, 2 vs. $0.45{\pm}0.13ng/100{\mu}L$ for TIMI flow 3, p<0.01) in acute coronary syndrome. In correlation analysis, the levels of APE1/Ref-1 were positively correlated with Troponin I (r=0.222; p<0.0001) and N-terminal pro-B type natriuretic peptide (NT-proBNP, r=0.217; p<0.0001) but not high sensitivity to C-reactive protein. Also, they revealed a negative correlation with ejection fraction (EF, r=-0.221; p=0.002). However, there were no significant differences among the three groups, were divided by their levels of APE1/Ref-1, for major adverse cardiovascular events (death, recurrent MI, stroke, revascularization) (8.2 vs. 14.0 vs. 12.5%, p=ns). Conclusion: The levels of serum APE1/Ref-1 are elevated in CAD, and are higher in MI than in angina. They are correlated with Troponin I, NT-proBNP, and EF.