title: Angiogenesis and antifibrotic action by hepatocyte growth factor in cardiomyopathy.
abstract: Impairment of cardiac function in cardiomyopathy has been postulated to be related to decreased blood blow and increased collagen synthesis. Therefore, a therapeutic approach to alter the blood flow or fibrosis directly by means of growth factors may open a new therapeutic concept in dilated cardiomyopathy. From this viewpoint, hepatocyte growth factor (HGF) is a unique growth factor with antifibrosis and angiogenesis effects. Using the hereditary cardiomyopathic Syrian hamster as a model of genetically determined cardiomyopathy and heart failure, the effects of overexpression of HGF on fibrosis and microvascular dysfunction were examined. HGF gene or control vector was injected by the Hemagglutinating Virus of Japan-liposome method into the anterior heart of cardiomyopathic hamsters (Bio 14.6) under echocardiography once a week, from 12 to 20 weeks of age (total, 8 times). Blood flow, as assessed by a laser Doppler imager score, and the capillary density in hearts, as assessed by alkaline phosphatase staining, were significantly increased in hamsters transfected with HGF gene compared with control-vector-transfected hamsters (P<0.01). In contrast, the fibrotic area was significantly decreased in hamsters transfected with HGF gene compared with control (P<0.01). Overall, in vivo experiments demonstrated that transfection of HGF gene into the myocardium of cardiomyopathic hamsters stimulated blood flow through the induction of angiogenesis and reduction of fibrosis. These results suggest that HGF gene transfer may be useful to protect against myocardial injury in cardiomyopathy through its cardioprotective effects such as antifibrosis and angiogenesis actions.
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Taniyama
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.forename: Motokuni
authors.initials: M
authors.lastname: Aoki
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hiraoka
authors.forename: Keita
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Naotaka
authors.initials: N
authors.lastname: Hashiya
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000503:physiopathology*; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006224:Cricetinae; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D007273:Injections, Intramuscular; D008647:Mesocricetus; D010957:Plasmids / Q000008:administration & dosage; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D017228:Hepatocyte Growth Factor