Abstract 12335: Urinary 8-hydroxy-2'-deoxyguanosine as a Novel Marker of Left Ventricular Remodelling in Patients With Dilated Cardiomyopathy
Background: Recently we reported that urinary 8-hydroxy-2' deoxyguanosine (8-OHdG), a marker of oxidized DNA damage, which derived from failing cardiac tissue, reflected well the severity of chronic heart failure. If urinary 8-OhdG levels represent myocardial oxidative stress in patients with dilated cardiomyopathy (DCM), it may become a useful marker of left ventricular (LV) remodeling. Here, we investigated whether the 8-OHdG level was related to LV remodeling in DCM patients in comparison with plasma brain natriuretic peptide (BNP).
Methods: We performed full study of cardiac catheterization including endomyocardial biopsy from LV and blood sampling from coronary sinus (CS) and aortic root (Ao) in 40 patients with DCM (LV ejection fraction (LVEF)=28±5%). We measured each serum concentration of 8-OHdG with ELISA method in blood samples from CS and Ao to clarify the source of 8-OHdG. Biopsy samples were stained with collagen-specific sirius red to evaluate myocardial fibrosis, and also stained with immunohistochemical method using anti-8-OHdG antibody to evaluate intracellular oxidative stress. In 150 DCM patients, moreover, we examined whether urinary 8-OHdG levels were correlated with LVEF, LV end-diastolic volume index(LVEDVI) and LV mass index(LVMI), e’(mitral annular early diastolic velocity).
Results: Blood sampling data showed that serum 8-OHdG level in CS was significantly higher than that in Ao in DCM (n=40; serum 8-OHdG: 0.65±0.52 ng/ml in CS vs 0.30±0.2 ng/ml in Ao, P<0.001), whereas it was not in normal subjects (n=10). Immunohistochemical study showed that the positive staining ratio of nuclei with anti-8OHdG in cardiomyocytes and CVF were significantly increased in patients with DCM as compared with normal subjects. A direct correlation was found between the positive staining ratio of nuclei and CVF (n=40, r=0.64, P<0.001). In the clinical study, urinary 8-OHdG was also significantly higher in DCM patients than in control subjects (DCM; n=150: 13.5±3.0 ng/mg creatinine vs. control; n=30: 8.0±2.1 ng/mg creatinine, P<0.001). There was a significant correlation between U-8-OHdG and LVEF, or LVEDVI, e’.
Conclusions: These findings suggest that urinary 8-OHdG may be a clinically-useful marker for LV remodeling associated with DCM.
- © 2012 by American Heart Association, Inc.