Right ventricle from human failing heart is less protected than left ventricle against oxidative stress damage

Purpose: During pathophysiological conditions, the balance between free radicals and antioxidants may shift towards a relative increase of free radicals resulting in oxidative stress. Conflicting data are available on antioxidant defences in human failing heart and they are limited to the left ventricle..We aimed to investigate and compare the source of oxidant and antioxidant enzyme activities in the right (RV) and left (LV) ventricles of human failing hearts, Methods: The molecular and biochemical analyses were performed in RV and LV from non failing (NF) (n=5) and failing hearts secondary to idiopathic dilated cardiomyopathy or ischemic heart disease (n=13). NADPH oxidase activity was determined by lucigenlnenhanced chemiluminescence and NOX2 and NOX4 gene expression by real-time PCR. The analysis of catalase (CAT), glutathione peroxidase (GPx) and Mn-superoxide dismutase (Mn-SOD) was peÉormed by measuring their mRNA (by real-time PCR) and protein levels (by Western blotting) as well as their enzymatic activities (by spectrophotometric methods). The level of lipid peroxidation was evaluated by measuring the contents of malonyldialdheyde (MDA). Results: A significant increase in NADPH-dependent superoxide production was found in both failing ventricles, more marked in RV. As for antioxidant enzymes, despite unchanged mRNA or protein expression, the enzymatic activity of CAT and GPx was lncreased, whereas Mn-SOD activity appeared decreased. We attributed the changes in . catalytic activity of these antioxidant enzymes to post-translational modifications (notably, tyrosine phosphorylation). The increase in NADPH oxidase-dependent superoxide production positively and significantly correlated with the activation of both CAT and GPx. However, the slope of the linear correlation (m) was steeper in LV than in RV forGPx (LV: m = 2.4L6i RV: m = 1.485) and CAT(LV: m = 1.007; RV: m = 0.354). MDA levels, measured as an indirect index of oxidative stress, were significantly higher in the RV than LV. Conclusions: We concluded that in human failing RV and LV, oxidative stress was correlated to activation of antioxidant enzymes CAT and GPx. This activation appeared less evident in RV than RV. Thus, although qualitatively similar changes appeared ln both the RV and LV of the same heafts, our data suggest a reduced protection of RV against oxidative stress damage and support the involvement of the right ventricle in the pathophysiology of heart disease.