The molecular basis for heart failure is unknown, but oxidative stress is associated with the pathogenesis of the disease. We tested the hypothesis that the activity of xanthine oxidoreductase (XOR), a free-radical generating enzyme, increases in hypertrophied and failing heart. We studied XOR in two rat models: (1) The monocrotaline-induced right ventricular hypertrophy and failure model; (2) coronary artery ligation induced heart failure, with left ventricular failure and compensatory right ventricular hypertrophy at different stages at 3 and 8 weeks post-infarction, respectively. XOR activity was measured at 30 degrees C and the reaction products were analysed by HPLC. In both models XOR activity in hypertrophic and control ventricles was similar. In the monocrotaline model, the hearts showed enhanced XOR activity in the failing right ventricle (65+/-5 mU/g w/w), as compared to that in the unaffected left ventricle (47+/-3 mU/g P<0.05, n=6-7). In the coronary ligation model, XOR activities did not differ at 3 and 8 weeks. In the infarcted left ventricle, XOR activity increased from 29.4+/-1.4 mU/g (n=6) in sham-operated rats, to 48+/-3 and 80+/-6 mU/g (n=8 P<0.05 v sham) in the viable and infarcted parts of failing rat hearts, respectively. With affinity-purified polyclonal antibody, XOR was localized in CD68+ inflammatory cells of which the number increased more in the failing than in sham-operated hearts. Our results show that the expression of functional XOR is elevated in failing but not in hypertrophic ventricles, suggesting its potential role in the transition from cardiac hypertrophy into failure.
Enhanced expression and activity of xanthine oxidoreductase in the failing heart.
CECONI, Claudio
2000
Abstract
The molecular basis for heart failure is unknown, but oxidative stress is associated with the pathogenesis of the disease. We tested the hypothesis that the activity of xanthine oxidoreductase (XOR), a free-radical generating enzyme, increases in hypertrophied and failing heart. We studied XOR in two rat models: (1) The monocrotaline-induced right ventricular hypertrophy and failure model; (2) coronary artery ligation induced heart failure, with left ventricular failure and compensatory right ventricular hypertrophy at different stages at 3 and 8 weeks post-infarction, respectively. XOR activity was measured at 30 degrees C and the reaction products were analysed by HPLC. In both models XOR activity in hypertrophic and control ventricles was similar. In the monocrotaline model, the hearts showed enhanced XOR activity in the failing right ventricle (65+/-5 mU/g w/w), as compared to that in the unaffected left ventricle (47+/-3 mU/g P<0.05, n=6-7). In the coronary ligation model, XOR activities did not differ at 3 and 8 weeks. In the infarcted left ventricle, XOR activity increased from 29.4+/-1.4 mU/g (n=6) in sham-operated rats, to 48+/-3 and 80+/-6 mU/g (n=8 P<0.05 v sham) in the viable and infarcted parts of failing rat hearts, respectively. With affinity-purified polyclonal antibody, XOR was localized in CD68+ inflammatory cells of which the number increased more in the failing than in sham-operated hearts. Our results show that the expression of functional XOR is elevated in failing but not in hypertrophic ventricles, suggesting its potential role in the transition from cardiac hypertrophy into failure.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
