title: Effects of hepatocyte growth factor in myocarditis rats induced by immunization with porcine cardiac myosin.
abstract: OBJECTIVE
  Myocarditis is considered one of the major causes of dilated cardiomyopathy. Hepatocyte growth factor (HGF) has pleiotropic activities that promote tissue regeneration and facilitate functional improvement of injured tissue. We investigated whether the epicardial sustained-release of HGF, using gelatin hydrogel sheets, improves cardiac function in a chronic myocarditis rat model.
  
  
  METHODS
  Six weeks after Lewis rats were immunized with porcine cardiac myosin to establish autoimmune myocarditis, HGF- or normal saline (NS)-incorporated gelatin hydrogel sheets were applied to the epicardium (G-HGF and G-NS, respectively). At either 2 or 4 weeks after treatment, these were compared with the Control myocarditis group. Cardiac function was evaluated by echocardiography and cardiac catheterization. Development of fibrosis was determined by histological study and expression of transforming growth factor-β1 (TGF-β1). Bax and Bcl-2 levels were measured to evaluate apoptotic activity.
  
  
  RESULTS
  At both points, fractional shortening and end-systolic elastance were higher in the G-HGF group than in the Control and G-NS groups (P < 0.01). Fractional shortening at 2 weeks of each group were as follows: 31.0 ± 0.9%, 24.8 ± 2.7% and 48.6 ± 2.6% (Control, G-NS and G-HGF, respectively). The ratio of the fibrotic area of the myocardium was lower in the G-HGF group than in the Control and G-NS groups at 2 weeks (G-HGF, 8.8 ± 0.9%; Control, 17.5 ± 0.2%; G-NS, 15.6 ± 0.7%; P < 0.01). The ratio at 4 weeks was lower in the G-HGF group than in the G-NS group (10.9 ± 1.4% vs 18.5 ± 1.3%; P < 0.01). The mRNA expression of TGF-β1 in the G-HGF group was lower than in the Control group at 2 weeks (0.6 ± 0.1 vs 1.1 ± 0.2) and lower than that in the G-NS group at 4 weeks (0.7 ± 0.1 vs 1.3 ± 0.2). The Bax-to-Bcl-2 ratios at both points were lower in the G-HGF group than in the Control group.
  
  
  CONCLUSIONS
  Sustained-released HGF markedly improves cardiac function in chronic myocarditis rats. The antifibrotic and antiapoptotic actions of HGF may contribute to the improvement. HGF-incorporated gelatin hydrogel sheet can be a new therapeutic modality for myocarditis.
authors: Department of Cardiovascular Surgery, Kyoto University, Graduate School of Medicine, Kyoto, Japan.
authors: Jota
authors: J
authors: Nakano
authors: Akira
authors: A
authors: Marui
authors: Hiroyuki
authors: H
authors: Muranaka
authors: Hidetoshi
authors: H
authors: Masumoto
authors: Hisashi
authors: H
authors: Noma
authors: Yasuhiko
authors: Y
authors: Tabata
authors: Akio
authors: A
authors: Ido
authors: Hirohito
authors: H
authors: Tsubouchi
authors: Tadashi
authors: T
authors: Ikeda
authors: Ryuzo
authors: R
authors: Sakata
mesh_terms: D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D024722:Cardiac Myosins / Q000276:immunology*; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D005355:Fibrosis; D005780:Gelatin / Q000737:chemistry; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D020100:Hydrogels; D007114:Immunization; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009205:Myocarditis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013552:Swine; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D002317:Cardiovascular Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C066855:HGF protein, human; D020100:Hydrogels; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D017228:Hepatocyte Growth Factor; D005780:Gelatin; D024722:Cardiac Myosins
keywords: Fibrosis; Growth substances; Myocarditis