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

Circ J. 2006 Aug;70(8):1001-5. doi: 10.1253/circj.70.1001.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adrenergic beta-Antagonists / pharmacology
  • Adult
  • Aged
  • Biomarkers / blood
  • Carbazoles / pharmacology
  • Cardiac Output, Low / blood*
  • Cardiac Output, Low / drug therapy
  • Cardiac Output, Low / physiopathology*
  • Carvedilol
  • DNA Damage / drug effects
  • DNA Damage / physiology*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / blood
  • Female
  • Heart / drug effects
  • Heart / physiopathology
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Myocardium / metabolism*
  • Oxidative Stress*
  • Propanolamines / pharmacology

Substances

  • Adrenergic beta-Antagonists
  • Biomarkers
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine