title: Upregulation of redox-regulating protein, thioredoxin, in endomyocardial biopsy samples of patients with myocarditis and cardiomyopathies.
abstract: An important role of redox regulation in myocardial diseases and heart failure has been postulated. Thioredoxin (TRX) is a redox-regulating protein. Recent studies indicated a possible association between plasma TRX concentrations and the severity of heart failure. Accordingly, we investigated the myocardial expression of TRX in patients with myocarditis and cardiomyopathies. Four cases of hypertrophic cardiomyopathy (HCM), 10 of dilated cardiomyopathy (DCM), 6 of myocarditis, and 5 of controls were studied. Right and left ventricular endomyocardial biopsy samples were obtained at the diagnostic cardiac catheterization. The samples were processed for immunohistological staining for TRX, which was done by the indirect immunoperoxidase technique. 8-hydoxy-2'-deoxyguanosine (8-OHdG), one of the major DNA base-modified products, was also detected for an established marker for oxidative stress. TRX immunoreactivity was none or trivial in control specimens. Positive TRX staining was found in 6 cases; 3 in active myocarditis and 3 in DCM. The positive staining was found in infiltrating cells and damaged myocytes in the perinecrotic lesions. Damaged myocytes were also positive for 8-OHdG All the 3 cases of DCM positive for TRX stain showed severe left ventricular hypertrophy on electrocardiogram and highly elevated left ventricular end-diastolic pressure (> 24 mmHg), suggesting the overload of oxidative stress by hemodynamic impairment. Myocardial TRX was upregulated in myocarditis and cardiomyopathies with active necrotic stage associated with DNA damage, which may reflect the oxidative stress overload in hemodynamically uncontrolled status.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nimata
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kishimoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shioji
authors.forename: Katsumi
authors.initials: K
authors.lastname: Ishizaki
authors.forename: Shoji
authors.initials: S
authors.lastname: Kitaguchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Norikazu
authors.initials: N
authors.lastname: Nagata
authors.forename: Chuichi
authors.initials: C
authors.lastname: Kawai
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D001706:Biopsy; D009202:Cardiomyopathies / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003971:Diastole; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D009205:Myocarditis / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009336:Necrosis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011312:Pressure; D013879:Thioredoxins / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D013879:Thioredoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine