Enhanced expression of the ubiquitin-proteasome system in the myocardium from patients with dilated cardiomyopathy referred for left ventriculoplasty: an immunohistochemical study with special reference to oxidative stress.
The ubiquitin (Ub)-proteasome system (UPS) is an important proteolytic mechanism for selecting and digesting cytotoxic proteins. The aim of this study is to elucidate expression and in situ localization of the UPS in the myocardium from patients with dilated cardiomyopathy (DCM) with refractory heart failure. The expression profile of the oxidative stress-induced cytotoxic proteins was also examined. Myocardium was obtained from 26 patients with DCM at the left ventriculoplasty. Ten normal autopsied hearts served as controls. Myocardial expressions of Ub and proteasomes were studied immunohistochemically. Oxidative stresses were examined in point of localization of the oxidation-induced modifier molecules (OMM). The relationship between immunohistochemical results and clinical parameters was also evaluated. Both Ub and proteasomes were stained positive in granular structures accumulating between the myofibrils and adjacent to nuclei in cardiomyocytes. The OMMs were also positive in the same Ub-positive granular structures. The area fraction of Ub, proteasomes and OMM was significantly higher in DCM hearts than in normal controls. Significant positive correlation was observed between the area fractions of Ub and plasma levels of brain natriuretic peptide (p = 0.046) in DCM hearts. In conclusion, enhanced expression of the UPS colocalized with OMM in cardiomyocytes may be involved in the pathophysiology of DCM hearts.
Otsuka
Koji
K
Department of Internal Medicine III, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki 569-8686, Japan.
Terasaki
Fumio
F
Shimomura
Hiroaki
H
Tsukada
Bin
B
Horii
Taiko
T
Isomura
Tadashi
T
Suma
Hisayoshi
H
Shibayama
Yuro
Y
Kitaura
Yasushi
Y
D000328:Adult; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000201:enzymology* / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000032:analysis*; D012017:Referral and Consultation; D025801:Ubiquitin / Q000032:analysis*; D015854:Up-Regulation
D015415:Biomarkers; D025801:Ubiquitin; D020097:Natriuretic Peptide, Brain; D046988:Proteasome Endopeptidase Complex