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.


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.
Kono
Yasuyuki
Y
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, and Division of Cardiology, National Hospital Organization Okayama-Medical Center, Japan. y-kono@gk9.so-net.ne.jp
Nakamura
Kazufumi
K
Kimura
Hideo
H
Nishii
Nobuhiro
N
Watanabe
Atsuyuki
A
Banba
Kimikazu
K
Miura
Aya
A
Nagase
Satoshi
S
Sakuragi
Satoru
S
Kusano
Kengo Fukushima
KF
Matsubara
Hiromi
H
Ohe
Tohru
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002227:Carbazoles / Q000494:pharmacology; D002303:Cardiac Output, Low / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D000077261:Carvedilol; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D011412:Propanolamines / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine