Elevated Levels of Oxidative DNA Damage in Serum and Myocardium of Patients With Heart Failure

• Published in: Circulation Journal 2006, Vol.70(8), pp.1001-1005
• Main Authors: Kono, Yasuyuki, Nakamura, Kazufumi, Kimura, Hideo, Nishii, Nobuhiro, Watanabe, Atsuyuki, Banba, Kimikazu, Miura, Aya, Nagase, Satoshi, Sakuragi, Satoru, Kusano, Kengo Fukushima, Matsubara, Hiromi, Ohe, Tohru
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adult; Aged; Biomarkers - blood; Carbazoles - pharmacology; Cardiac Output, Low - blood; Cardiac Output, Low - drug therapy; Cardiac Output, Low - physiopathology; Carvedilol; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - blood; DNA; DNA Damage - drug effects; DNA Damage - physiology; Female; Heart - drug effects; Heart - physiopathology; Heart failure; Heart Rate - drug effects; Heart Rate - physiology; Humans; Immunohistochemistry; Male; Middle Aged; Myocardium - metabolism; Oxidative Stress; Propanolamines - pharmacology
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.70.1001

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 β-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. (Circ J 2006; 70: 1001 - 1005)