Elevated levels of DNA damage due to oxidative stress in serum and myocardium of patients with heart failure

Abstract

Background: We hypothesized that oxidative damage to DNA might be associated with progression of heart failure. We investigated whether the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were elevated in serum and myocardium of patients with cardiomyopathies. Methods and Results: Serum levels of 8-OHdG were measured by enzyme immunoassay in 58 patients with dilated cardiomyopathy (DCM) and 23 patients with hypertrophic cardiomyopathy (HCM) and in 20 control subjects. DCM patients had significantly elevated serum levels of 8-OHdG compared with those in control subjects and HCM patients (DCM: 5.2 ± 2.9 ng/mL vs. control: 3.0 ± 1.5 ng/mL, P = 0.0004; DCM vs. HCM: 2.6 ± 0.8 ng/mL, P < 0.0001). The serum levels were significantly correlated with left ventricular end-diastolic diameter determined by echocardiography (P = 0.0009). The levels were significantly inversely correlated with left ventricular ejection fraction determined by left ventriculography (P = 0.0002). Endomyocardial biopsy samples obtained from 12 DCM patients and 5 control subjects with normal cardiac function were studied immunohistochemically for the expression of 8-OHdG. Positive 8-OHdG staining was found in the nuclei of cardiac myocytes of samples from DCM patients but not in those from control subjects. After treatment with carvedilol, the serum levels of 8-OHdG in DCM patients decreased by 19% (P < 0.05) along with amelioration of heart failure. Conclusion: These results indicate that DNA damage due to oxidative stress is implicated in progression of heart failure.