Elevated levels of oxidative DNA damage in serum and myocardium of patients with heart failure.

BACKGROUND Oxidative stress has been implicated in the pathogenesis of chronic heart failure. The present study 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), and 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 immunoassay in 56 patients with DCM and in 20 control subjects. DCM patients had significantly elevated serum levels of 8-OHdG compared with control subjects. 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 significantly decreased by 19%, together with amelioration of heart failure. CONCLUSIONS Levels of 8-OHdG are elevated in the serum and myocardium of patients with heart failure. Treatment with carvedilol might be effective for decreasing the oxidative DNA damage.