Abstract 3748: Elevated Levels of Oxidative DNA Damage in Serum and Myocardium of Patients with Heart Failure
Background: Oxidative stress due to reactive oxygen species (ROS) has been implicated in the pathogenesis of heart failure. DNA in the nucleus is one of the major targets of ROS. Oxidative DNA damage has been implicated in the pathogenesis of cancer and neurodegenerative diseases and in aging. Therefore, we hypothesized that oxidative DNA damage was elevated in patients with heart failure. To test this hypothesis, we investigated whether the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were elevated in the serum and myocardium of patients with dilated cardiomyopathy (DCM), furthermore whether carvedilol, a vasodilating beta-blocker with antioxidant activity, could reduce the levels.
Methods and Results: Serum levels of 8-OHdG were measured by enzyme immuno-assay in 56 patients with DCM (42 men and 14 women) and in 20 control subjects. DCM patients had significantly elevated serum levels of 8-OHdG compared with those in control subjects (DCM: 5.2±2.9 ng/mL versus control: 3.0±1.5 ng/mL, P<0.0018). There was no significant difference between the levels in male and female patients (men: 6.1±4.3 ng/mL vs. women: 4.9±2.3 ng/mL, P=NS). 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 cardiomyocytes from DCM patients but not in those from control subjects. After treatment with carvedilol, the serum levels of 8-OHdG in DCM patients were significantly decreased along with amelioration of heart failure (6.3±3.5 ng/mL before and 5.1±3.2 ng/mL after carvedilol administration, P<0.05).
Conclusions: The levels of oxidative DNA damage are elevated in serum and myocardium of patients with heart failure. Treatment with carvedilol might be effective for decreasing the oxidative DNA damage.