Reorganization of cytoskeletal proteins and prolonged life expectancy caused by hepatocyte growth factor in a hamster model of late-phase dilated cardiomyopathy.
OBJECTIVE
It has been postulated recently that changes in cytoskeletal and sarcolemmal proteins initiate a final common pathway for contractile dysfunction in dilated cardiomyopathy. In ischemic cardiomyopathy, hepatocyte growth factor plays an important role in reorganizing the impaired cytoskeletal proteins in several cell types. We have tested the hypothesis that hepatocyte growth factor might improve life expectancy through modification of the molecular process that contributes to impairment in dilated cardiomyopathy.


METHODS
Adult male 27-week-old BIO TO-2 hamsters, which show moderate cardiac remodeling, were divided into treatment groups that received (1) hemagglutinating virus of Japan liposomes containing human hepatocyte growth factor cDNA (H group), (2) culture medium (C group), or (3) sham operation (S group).


RESULTS
After the operation, echocardiography demonstrated that the enlarged left ventricular end-systolic dimension and decreased fractional shortening were significantly attenuated in the H group compared with the C group. There was significantly less myocardial fibrosis in the H group compared with the C group. Immunohistochemical analysis showed alpha-dystroglycan and alpha- and beta-sarcoglycan expression in the basement membrane beneath the cardiomyocytes in the H group, whereas no expression of these proteins was seen in the C group. The 40-week survival was significantly better in the H group than in the C and S groups.


CONCLUSIONS
An improved survival associated with transient reorganization of the cytoskeletal proteins and reduction in myocardial fibrosis was achieved by hepatocyte growth factor treatment in an adult hamster model of dilated cardiomyopathy. The results suggest a therapeutic potential of hepatocyte growth factor in the treatment of dilated cardiomyopathy.
Kondoh
Haruhiko
H
Division of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Japan.
Sawa
Yoshiki
Y
Fukushima
Norihide
N
Matsumiya
Goro
G
Miyagawa
Shigeru
S
Kitagawa-Sakakida
Satoru
S
Memon
Imran A
IA
Kawaguchi
Naomasa
N
Matsuura
Nariaki
N
Matsuda
Hikaru
H
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D008017:Life Expectancy; D008297:Male; D023421:Models, Animal; D020257:Ventricular Remodeling / Q000502:physiology
D003598:Cytoskeletal Proteins; D017228:Hepatocyte Growth Factor