Core protein of hepatitis C virus induces cardiomyopathy.
Hepatitis C virus (HCV) has been reported to be associated with cardiomyopathy. However, the mechanism of cardiomyopathy in chronic HCV infection is still unclear. Therefore, we investigate the development of cardiomyopathy in mice transgenic for the HCV-core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction assessed by Doppler echocardiography. Histologically, hypertrophy of cardiomyocytes, cardiac fibrosis, disarray and scarcity of myofibrils, vacuolization and deformity of nuclei, myofibrillar lysis, streaming of Z-bands, and an increased number of bizarre-shaped mitochondria were found in HCV-core transgenic mice. These histological changes are just consistent with cardiomyopathy. In conclusion, the HCV-core protein directly plays an important role in the development of cardiomyopathy.
Omura
Takashi
T
Department of Internal Medicine and Cardiology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. omura@med.osaka-cu.ac.jp
Yoshiyama
Minoru
M
Hayashi
Tetsuya
T
Nishiguchi
Shuhei
S
Kaito
Masahiko
M
Horiike
Shinichiro
S
Fukuda
Katsuhiko
K
Inamoto
Sakiko
S
Kitaura
Yasushi
Y
Nakamura
Yasuhiro
Y
Teragaki
Masakazu
M
Tokuhisa
Takeshi
T
Iwao
Hiroshi
H
Takeuchi
Kazuhide
K
Yoshikawa
Junichi
J
D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D001794:Blood Pressure; D001835:Body Weight; D015150:Echocardiography, Doppler; D005355:Fibrosis; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity*; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008929:Mitochondria, Heart / Q000378:metabolism / Q000648:ultrastructure; D009205:Myocarditis / Q000150:complications*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000648:ultrastructure; D016328:NF-kappa B / Q000032:analysis; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics; D009929:Organ Size; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000473:pathology; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D016328:NF-kappa B; D012333:RNA, Messenger; D012367:RNA, Viral; D018808:Transcription Factor AP-1; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor